NCEN Language performance in Al zheimer’s disease and mild ...

JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY2008, 30 (5), 501–556

© 2007 Psychology Press, an imprint of the Taylor & Francis Group, an Informa business

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NCENLanguage performance in Alzheimer’s disease and mild cognitive impairment: A comparative review

Language Performance In Mci and Ad Vanessa Taler and Natalie A. Phillips

Department of Psychology/Centre for Research in Human Development, Concordia University, Montréal, Québec, Canada, and Bloomfield Centre for Research on Aging, Montréal, Québec, Canada

Mild cognitive impairment (MCI) manifests as memory impairment in the absence of dementia and progresses toAlzheimer’s disease (AD) at a rate of around 15% per annum, versus 1–2% in the general population. It thusconstitutes a primary target for investigation of early markers of AD. Language deficits occur early in AD, andperformance on verbal tasks is an important diagnostic criterion for both AD and MCI. We review language per-formance in MCI, compare these findings to those seen in AD, and identify the primary issues in understandinglanguage performance in MCI and selecting tasks with diagnostic and prognostic value.

INTRODUCTION

Increased life expectancy worldwide has resulted inan increased number of individuals at risk of orsuffering from Alzheimer’s disease (AD), resultingin significant financial and emotional burden forsufferers and their families. Intense research inter-est has thus focused on identifying elderly individ-uals who will develop AD, both to commencepharmacological treatment as early as possible inthe disease course and to allow psychological inter-vention and family and financial planning.

A considerable body of evidence suggests that aprodromal, or preclinical, phase of AD may occuryears before diagnosis. At this stage, alterationscan be detected at both the neuropathological andthe cognitive level. Neuropathological changes areseen in the entorhinal cortex very early in the dis-ease course. Marked neuronal loss (32%) in thisregion can be observed in very mild or questiona-ble AD, as can neurofibrillary tangles and senileplaques in sufficient quantities for a diagnosis ofAD (Gómez-Isla & Hyman, 2003). Increased tauphosphorylation, resulting in the formation of neu-rofibrillary tangles, is one of the earliest markers ofAD and occurs prior to dementia onset (for a

review, see Iqbal et al., 2005). Similarly, volumetricMRI studies have suggested that hippocampalatrophy is seen before dementia onset (Fox,Warrington, Stevens, & Rossor, 1996; Jack et al.,1999; Jack et al., 1997; Visser et al., 1999), and thatthis atrophy progresses subsequent to clinicallyidentifiable dementia (Fox et al., 1996).

Individuals with preclinical AD also manifestalterations in various cognitive domains. Deficitsare seen in episodic memory (Bäckman, Small, &Fratiglioni, 2001; Chen et al., 2001; Elias et al.,2000; Small, Herlitz, Fratiglioni, Almkvist, &Bäckman, 1997; Tierney et al., 1996), executivefunction (Albert, Moss, Tanzi, & Jones, 2001;Chen et al., 2001; Daly et al., 2000), perceptualspeed (Albert et al., 2001, Fabrigoule et al., 1998;Fox, Warrington, Seiffer, Agnew, & Rossor, 1998),verbal ability (Convit et al., 2000; Grober &Kawas, 1997; Jacobs et al., 1995; Linn et al., 1995;Small et al., 1997), visuospatial skill (Albert et al.,2001; Chen et al., 2001; Fowler, Saling, Conway,Semple, & Louis, 2002; Howieson et al., 1997), andattention (Nielsen, Lolk, Andersen, Andersen, &Kragh-Sorenson, 1999; Rubin et al., 1998; Tierneyet al., 1996). As is the focus of this review, deficitsare also observed in the domain of language.

V.T. is supported by a postdoctoral fellowship awarded by the Alzheimer’s Society of Canada/ Fonds de recherche en santé du Québec.Address correspondence to Natalie A. Phillips, Department of Psychology, Concordia University, 7141 Sherbrooke Street West,

Montréal, Québec, Canada H4B 1R6 (E-mail: [email protected]).

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502 TALER AND PHILLIPS

A number of terms have been used to describeindividuals who exhibit cognitive dysfunction inthe absence of dementia. Kral (1962) proposed theterm benign senescent forgetfulness. Other termsthat have been proposed include age-associatedmemory impairment (AAMI; Crook et al., 1986)and age-associated cognitive decline (AACD; Levy,1994). However, these terms are generally intendedto denote individuals at the extremes of normalaging, rather than those in a preclinical stage ofdementia. Some studies have found increased ratesof conversion to dementia in these groups (Lane &Snowdon, 1989; Richards, Touchon, Ledesert, &Ritchie, 1999), while others have found similarrates in these individuals and in healthy elderlysubjects (Hanninen et al., 1995). The term cognitiveimpairment, no dementia (CIND; Graham et al.,1997) connotes an underlying pathological state,although the underlying etiologies may be varia-ble, resulting in a lack of specificity (Rivas-Vasquez, Mendez, Rey, & Carrazana, 2004).

A recently introduced term designed to capturethe point on the spectrum of cognitive functionbetween healthy aging and dementia is mild cogni-tive impairment (MCI). This term was first used byFlicker, Ferris, and Reisberg (1991) to describeindividuals with a Global Deterioration Scale(GDS, Reisberg, Ferris, de Leon, & Crook, 1982)rating of 3. However, it was Petersen et al. (1999)who first set out formal criteria for a diagnosis ofMCI. The criteria are as follows: (a) subjectivecomplaint of memory loss, (b) objective impair-ment of ability, (c) preserved general cognitivefunction, (d) intact activities of daily living, (e)individual does not meet criteria for dementia.Individuals who meet these criteria (henceforthreferred to as the “Petersen criteria”) are at anincreased risk for developing AD relative to thegeneral population. In an extensive literaturereview utilizing these criteria, Petersen et al.(2001b) found an average annual conversion rateof 14%, compared to 1–2% in the general popula-tion. Other groups have found higher conversionrates: Geslani, Tierney, Herrmann, and Szalai(2005) report a conversion rate of 41% after oneyear and 64% after two years.

It should be noted that, although there is someoverlap in the characteristics, constructs such asAAMI are not necessarily directly analogous withMCI. For example, Bartres-Faz et al. (2001) con-ducted a study examining performance on a rangeof cognitive functions, including language, by indi-viduals meeting the diagnostic criteria for AAMI(n=93 of 104 individuals presenting with memorycomplaints) and MCI (n=63 of 104). They foundthat MCI individuals performed significantly

worse than AAMI individuals on a number oftasks, including memory, phonetic fluency, andnaming, and conclude that AAMI criteria, whileselecting a population that is genetically distinctfrom healthy elderly adults, nonetheless do notdelineate a population that is as impaired as thosemeeting the criteria for MCI. They suggest thatAAMI may represent a point on the continuum ofdecline that is earlier than that represented byMCI. In a similar vein, Ritchie, Artero, andTouchon (2001) compared the constructs ofAACD and MCI in a population-based study.MCI was estimated to have a prevalence of 3.2%and AACD 19.3%. It was found that MCI was apoor predictor of dementia over a 3-year period,manifesting temporal instability. AACD showedbetter stability and high predictive validity, despitethe fact that it has been conceptualized as a benignimpairment. Given these findings, comparisonsbetween results obtained with MCI individuals andthose diagnosed with similar syndromes should beundertaken with caution.

While it is generally accepted that MCI representsa risk factor for AD, there still exists controversy asto whether MCI individuals will always convert toAD—that is, whether MCI always representsprodromal AD. For example, Chertkow, Verret,Bergman, Wolfson, & McKelvey (2001, cited inChertkow, 2002) found that 25% of their MCI sub-jects had not converted to AD even 10 years after theonset of memory problems. Patients at the MayoAlzheimer’s Disease Research Center converted atapproximately 12% per year, and after 6 years, 80%had converted (Petersen & Morris, 2003). Morris etal. (2001), on the other hand, found conversion ratesof 100% in the long term (9.5 years) in their group ofcognitively impaired individuals, and claim thatMCI always represents prodromal AD.

One possible explanation for these diverse find-ings may be the significant variability in criteriaused to establish a diagnosis of MCI (Chertkow,2002). Morris et al. (2001), who claim that MCIindividuals will always convert to AD, use as adiagnostic criterion a rating of 0.5 on the ClinicalDementia Rating Scale (CDR, Hughes, Berg,Danziger, Coben, & Martin, 1982), which corre-sponds to “questionable AD.” A second scale thathas been used is the Global Deterioration Scale(GDS; Reisberg et al., 1982); a score of 3 has beensuggested to represent MCI, where 1 is normal, 2 isnormal with subjective complaint, and 3 through 7denote increasing impairment (Kluger, Ferris,Golomb, Mittleman, & Reisberg, 1999). Otherresearchers assess MCI in terms of variance fromage- and education-matched norms; for example, acutoff score of 1.5 standard deviations below the


LANGUAGE PERFORMANCE IN MCI AND AD 503

mean in memory tests may be applied. Others relyon the judgment of the clinician (for a discussion ofthe implementation of diagnostic criteria, seePetersen, 2004).

Recently, the Stockholm consensus group(Winblad et al., 2004) proposed the followingrevised criteria for MCI:

1. The person is neither normal nor demented.2. There is evidence of cognitive deterioration

shown by either objectively measured declineover time and/or subjective report of decline byself and/or informant in conjunction withobjective cognitive deficits.

3. Activities of daily living are preserved, andcomplex instrumental functions are eitherintact or minimally impaired.

Artero, Petersen, Touchon, and Ritchie (2006)evaluated these revised criteria and concluded thatthey predicted transition to dementia significantlybetter than did the original Peterson criteria, par-ticularly when amnestic and nonamnestic MCIsubgroups were combined (area under the curve,AUC=0.80; sensitivity: 95%; specificity: 66%).Thus, the inclusion of impairment in domains inaddition to memory provides a better means toidentify those individuals who will convert todementia. However, the criteria cannot differenti-ate between the various dementias, such as AD,vascular dementia, and frontotemporal dementia.

A second consideration with respect to the diag-nosis of MCI is that considerable heterogeneity isobserved in this group. Petersen et al. (2001a) havepointed out that MCI may be divided into threesubgroups, depending on the cognitive functionsaffected. In amnestic MCI, only memory isaffected. In multiple-domain MCI, impairment isseen in multiple cognitive domains, but at a levelinsufficient to constitute dementia. Finally, a thirdsubtype, termed single nonmemory domain MCI,presents as a specific impairment in a nonmemorydomain. It should be noted that the “Petersen cri-teria” discussed above refer to the amnestic variantof MCI.

Heterogeneity is also seen in the etiology of thedisorder (Petersen, 2003). It has been suggestedthat amnestic MCI is likely to evolve to AD,multiple-domain MCI to AD or vascular dementia,and single nonmemory domain MCI to anothertype of dementia, such as frontotemporal demen-tia, Lewy body dementia, primary progressiveaphasia, or vascular dementia (Petersen, 2003).However, recent research (Fischer et al., 2007) sug-gests that MCI subtype is not a good predictor ofevolution to one type of dementia or another.

The goal of identifying those MCI individualswho are most likely to convert to AD will probablybest be met through implementation of a battery oftests designed to tap into a number of diverse indi-cators of AD, including a combination of geneticand cognitive markers, as well as findings fromvolumetric and functional neuroimaging, all ofwhich have proven useful in early detection of AD(for a review, see Chong & Sahadevan, 2005). It isthus of great importance to specify the perform-ance of MCI individuals across a variety of cogni-tive domains. Of particular interest arelongitudinal studies of cognitive decline, whereindividual performance is correlated with eventualconversion.

It is well documented that AD patients oftenmanifest deficits in language processing very earlyin the disease course. Deficits are seen in verbalfluency (for a review, see Henry, Crawford, &Phillips, 2004), naming (e.g., Bayles & Kaszniak,1987, Bayles, Tomoeda, & Trosset, 1992, Bowles,Obler, & Albert, 1987; Fisher, Rourke, & Bieliauskas,1999)—particularly of biological items (Fung et al.,2001; Whatmough et al., 2003)—semantic knowl-edge (Chertkow & Bub, 1990; Hodges, Salmon, &Butters, 1992a; Martin & Fedio, 1983), anddiscourse-level processing (for a review, seeCaramelli, Mansur, & Nitrini, 1998). Syntactic andphonological abilities, on the other hand, are typi-cally relatively preserved (Bayles, 1982; Bayles &Kaszniak, 1987; Irigaray, 1973; Kempler, Curtiss,& Jackson, 1987; Kertesz, 1994; Light & Burke,1993; Patel & Satz, 1994; Schwartz, Marin, &Saffran, 1979; Whitaker, 1976).

Given that language impairment is frequent inAD and occurs early in the disease course, webelieve that a review of the performance of MCIindividuals in language tasks is timely and will con-tribute to the goal of identifying early markers ofcognitive impairment in AD. While such tests can-not replace memory testing in these populations,they provide valuable additional information whenmaking a clinical judgment of the status of an indi-vidual. There exists evidence (e.g., Alexopoulos,Grimmer, Perneczky, Domes, & Kurz, 2006;Bozoki, Giordani, Heidebrink, Berent, & Foster,2001; Sacuiu, Sjögren, Johansson, Gustafson, &Skoog, 2005) that MCI individuals with impair-ments in multiple domains, including language, aremore likely to develop AD than are those with apure memory impairment. Thus, understandingthe nature of language impairment and possiblyidentifying sensitive measures of linguistic impair-ment constitute a vital tool in early detection of AD.

The current paper gives an overview of the find-ings in language performance in MCI published to



date. We review MCI individuals’ performance onstandardized neuropsychological tests, discussfindings in the experimental psycholinguistic litera-ture, and compare these findings to those reportedin the AD literature. We then offer suggestions forthe features that should be present in a test oflanguage performance that aims to identify pro-dromal AD.

Relevant references were identified through aMedline search using the following search terms:mild cognitive impairment; frontotemporal demen-tia, early diagnosis; alzheimer, early diagnosis;minimal alzheimer; very mild alzheimer, neuropsy-chology; questionable dementia; cognitive impair-ment no dementia, neuropsychology; ageassociated memory impairment, neuropsychology;age associated cognitive decline, neuropsychology;benign senescent forgetfulness. This was supple-mented by a hand search of the reference lists ofthe articles identified in the Medline search.

STANDARDIZED LANGUAGE TESTS

There are two aspects to consider when evaluatingthe utility of a standardized neuropsychologicaltest in the assessment of MCI individuals. First,does the test distinguish accurately between nor-mal aging, MCI, and AD? That is, does the testprovide diagnostic utility with respect to MCI? Sec-ond, does the test distinguish between those indi-viduals with MCI who will go on to develop ADand those who will not? In other words, does thetest provide prognostic utility? A number of stand-ardized language tests have been evaluated withrespect to these criteria; the following section out-lines the findings published in the literature todate.

Semantic processing

Most epidemiological studies of MCI include somemeasure of semantic processing, typically verbalfluency or picture-naming measures. Below wedescribe the primary findings with respect to MCIperformance on these tasks.

Verbal fluency

Verbal fluency tests are amongst the most widelyused measures of cognitive functioning in demen-tia. These tasks assess an individual’s ability toretrieve and produce words that conform to agiven criterion within a specified time period. Let-ter (phonemic) fluency involves the generation ofas many words as possible beginning with a given

letter (in English, usually F, A, or S). Category flu-ency involves the generation of as many words aspossible that fall into a given category (e.g., ani-mals). Both category and letter fluency impose sig-nificant demands on executive processes; subjectsmust organize verbal retrieval and recall, initiateresponses, and monitor prior responses, as well asinhibit inappropriate responses (Henry et al.,2004). However, the two tasks differ in terms of thesearch strategies required. Letter fluency relies onsearch strategies based on lexical representations,whereas category fluency requires a search forsemantic extensions of a superordinate term,meaning that semantic associations within the lexi-con must be intact in order for the task to be car-ried out successfully (Rohrer, Salmon, Wixted, &Paulsen, 1999).

Impairments in verbal fluency, and especially incategory fluency, are well documented in AD. Arecent meta-analysis of 153 studies with 15,990 ADparticipants examining semantic and letter fluency(Henry et al., 2004) found that, while AD individu-als’ performance on tests of both semantic and let-ter fluency was impaired relative to healthy elderlycontrols (p < .001 for both measures), the effectwas much larger for semantic fluency (r=.73) thanfor letter fluency (r=.55). There was no significantcorrelation between dementia severity and theseverity of the deficit in verbal fluency. Category,but not letter, fluency was correlated with verbalIQ (p < .021). Furthermore, performance on theBoston Naming Test (BNT), while strongly corre-lated with both fluency tasks, was more stronglycorrelated with category than with letter fluency(r=.50 and r=.68). The authors suggest that thespecific deficit in category fluency is due to the deg-radation of the semantic knowledge required forcategory fluency tests, while letter fluency tapssemantic memory to a lesser extent. A larger per-formance deficit was seen in the BNT than in theletter fluency test, whereas the deficit seen in thecategory fluency test was greater than that seen inthe BNT. Thus, since retrieval demands are equiv-alent for the two fluency tasks, and the BNT alsoimposes demands on semantic knowledge, prob-lems in effortful retrieval likely do not underlie thedeficit in category fluency.

The diagnostic utility of category fluency forAD, even very early in the disease course, is alsowell established (e.g., Caccapolo-Van Vliet et al.,2003; Cerhan et al., 2002; Duff Canning, Leach,Stuss, Ngo, & Black, 2004; Lam, Ho, Lui, & Tam,2006; Salmon et al., 2002); it yields a sensitivity of100% and a specificity of 92.5% (Monsch et al.,1992), and performance on this task has beenshown to decline with advancing AD (Perry,



Watson, & Hodges, 2000; Small & Bäckman,1998). Given the diagnostic utility of fluency tasks,as well as the fact that deficits are seen very early inthe disease course, a number of studies have under-taken to examine verbal fluency performance as apotential prognostic marker for AD and/or a diag-nostic marker for MCI. These studies have takenthe form of either longitudinal studies of individu-als who are initially nondemented, or studies ofindividuals who have been diagnosed with cogni-tive impairment. Summary statistics for these stud-ies are provided in Table 1, and the studiesthemselves are summarized in Appendix A.

Several prospective studies have found impair-ments in category fluency in healthy adults up to9 years prior to the onset of dementia (Amievaet al., 2005; Auriacombe et al., 2006; Chen et al.,2001; Fabrigoule et al., 1998; Hodges, Erzinçlioglu,& Patterson, 2006; Jorm, Masaki, Petrovitch,Webster Ross, & White, 2005; Masur, Sliwinski,Lipton, Blau, & Crystal, 1994; Nielsen et al., 1999;Small et al., 1997; Vogel, Gade, Stokholm, &Waldemar, 2005). Chen et al. (2001) found thatverbal fluency scores declined more steeply in pre-AD individuals than in controls (those whoremained nondemented for 10 years), particularlythose with higher education levels. Letter fluencyhas also been found to be a reliable predictor ofdementia onset in one study (Small et al., 1997),although other studies found that this was not thecase (Chen et al., 2001; Goldman et al., 2001).Likewise, a number of studies examining categoryfluency in nondemented individuals with cognitiveimpairment have demonstrated lower performanceon this task in those individuals who went on todevelop dementia than in those who did not(Blackwell et al., 2004; Guarch, Marcos, Salamero,& Blesa, 2004; Hanninen et al., 1995; Ritchie et al.,2001). Finally, MCI individuals who have a

memory impairment in addition to an impairmentin one of four other cognitive domains (includingnaming and letter fluency) have been found in onestudy to have an 8 times higher risk of progressingto AD after a 2-year interval than those who mani-fested a memory deficit alone (Bozoki et al., 2001).Another study found that MCI individuals withimpairments in multiple domains have over twicethe risk of conversion after 3.5 years (Alexopouloset al., 2006).

With respect to diagnostic utility, verbal fluencyhas been shown to discriminate accurately betweenMCI subjects and unimpaired control subjects(Bennett et al., 2002; Bschor, Kuhl, & Reischies,2001; Dwolatzky et al., 2003; Geslani et al., 2005;Grundman et al., 2004; Petersen et al., 1999;Ribeiro, de Mendonça, & Guerreiro, 2006; Tabertet al., 2006). One issue that arises with respect tothe various studies examining category fluency iswhether the use of different semantic categorieselicits comparable results. Cunje, Molloy, Standish,and Lewis (2007) tested verbal fluency performancein MCI individuals using four categories: animals,cities and towns, first names, and fruits andvegetables. No difference between categories wasseen in 60-second scores, indicating that the differ-ent versions of the category fluency task allow forserial testing. The use of different versions caneliminate a learning bias, whereby participantsshow a false improvement in performance due torecollection of categories and practice between ses-sions. The 60-second category fluency scoresshowed good sensitivity and specificity for differ-ences between healthy elderly and MCI individuals(area under the ROC curve=0.87 for animals, 0.78for cities and towns, 0.79 for fruits and vegetables,0.83 for names, p < .01 in all cases). Murphy, Rich,and Troyer (2006) found that MCI-amnestic(MCI-A) and AD individuals produced fewer

TABLE 1 Summary statistics for the studies presented in Appendices A and B

Test

Category fluency Letter fluency Naming

Studies reporting difference between NE and MCI/QD/preclinical dementia/miminal AD

29 8 22

Studies reporting no difference between NE and MCI/QD/preclinical dementia/minimal AD

3 8 13

Studies reporting difference between MCI/QD preclinical dementia/minimal AD and mild AD

17 4 12

Studies reporting no difference between MCI/QD and AD 0 5 5Studies reporting predictive value for AD 21 9 12Studies reporting no predictive value for AD 6 7 12

Note. AD=Alzheimer’s disease. NE=normal elderly. MCI=mild cognitive impairment. QD=questionable dementia.



items in semantic fluency than did healthy olderadults, while letter fluency was relatively preservedin the MCI-A group. Control and MCI-A partici-pants generated more items in category than letterfluency, while ADs exhibited the opposite pattern.In terms of clustering and switching, control andMCI-A participants performed similarly on letterfluency, while on semantic fluency, MCI-A par-ticipants’ performance was intermediate betweenthat of ADs and controls. Additionally, datafrom our lab indicate that deficits in switching inverbal fluency are equivalent in AD individualsand in MCIs who go on to develop AD, whileMCIs who do not convert to AD exhibit perform-ance similar to that of healthy elderly adults (Phillips,personal communication). Storandt, Grant, Miller,and Morris (2002) report that letter fluency scoresdecline faster with increasing impairment (definedby the CDR score).

Other studies have found that category fluencytasks are not sensitive to decline in MCI. LambonRalph, Patterson, Graham, Dawson, and Hodges(2003) found that MCI subjects showed onlyamnesia, and that impairments in language,including category fluency, did not manifest untilAD set in. Although the mean number of itemsgenerated was lower in the MCI group than in thecontrol group (36.97 vs. 44.26), this result did notreach significance. Karrasch, Sinervä, Grönholm,Rinne, and Laine (2005) found that verbal fluencymeasures distinguished between AD and controlsubjects, but did not distinguish between controland MCI subjects, nor between MCI and ADindividuals. Again, control subjects scored higheron average than MCI individuals (21.1 ± 3.8 vs.18.9 ± 5.9) who scored higher than ADs (18.9 ±5.9 vs. 14.3 ± 5.2), but this effect did not reachsignificance.

One important point in reconciling these con-flicting results is the question of diagnosis of MCI.If the MCI sample meets the criteria for amnesticMCI, as is the case in both the Lambon Ralph et al.(2003) and the Karrasch et al. (2005) studies, thenimpairment in a cognitive domain other than mem-ory constitutes an exclusionary criterion. Thus,deficits in language tasks such as category fluencywould not be expected. Lambon Ralph and col-leagues (2003) note that their sample was biasedtowards patients with no focal deficits in other cog-nitive domains. These investigators found that def-icits in semantic and linguistic domains emergedafter the memory deficits that are the hallmark ofMCI. This is consistent with the finding that MCIpatients with deficits in cognitive domains otherthan memory are more likely to convert to AD(Alexopoulos et al., 2006; Bozoki et al., 2001;

Sacuiu et al., 2005). Such patients are presumablymore advanced in the disease course, neuropathol-ogy having spread from the entorhinal cortex toencroach on areas of the inferior and lateral tem-poral neocortex.

There exist a few studies examining more fine-grained aspects of verbal fluency tasks in MCI.Cooper, Lacritz, Weiner, Rosenberg, and Cullum(2004) examined the effects of practice in test–retest conditions with a category fluency task. Ithas been previously established (Cooper et al.,2001) that AD individuals’ performance on an ani-mal fluency task does not improve with practice,even at a very short test–retest interval. Cooper et al.(2004) demonstrated that, like AD individuals,MCI individuals do not benefit from practice. Theauthors suggest that the reliability of category flu-ency measures in AD and MCI, in combinationwith the lack of practice effect, means that this taskmay be a useful cognitive marker for pharmacolog-ical studies requiring short intervals between test-ing sessions. Forbes-McKay, Ellis, Shanks, andVenneri (2005) examined the individual items pro-duced in a category fluency task by controls andminimal, mild, and moderate AD patients, andfound that age of acquisition of items reliably dif-ferentiated between healthy adults and ADpatients, although it was not sensitive to the sever-ity of AD. Gómez and White (2006) report thatmeasures other than number of items generateddiscriminate between healthy older adults and verymild AD patients—namely, clustering, switching,and size of cluster.

Östberg, Fernaeus, Hellström, Bogdanovic, andWahlund (2005) examined MCI individuals’ per-formance on a verb fluency task, in which theywere instructed to name as many things as possiblethat people do (as distinct from verbal fluency,described above, or verb generation, in which sub-jects are given nouns as stimuli and in responseproduce verbs). Verb fluency was found to be dis-proportionately impaired in MCI relative to nounand letter fluency; the authors suggest that thismay be because verb referents are not taxonomic inthe same way as noun referents, and verb fluencythus relies more on neocortical-hippocampal inter-action, particularly the perirhinal cortex, which isaffected by very early AD neuropathology.

In sum, deficits in verbal fluency have been dem-onstrated to be predictive of development ofdementia and to be present in MCI in a number ofstudies (see Table 1). Greater impairments are seenin category fluency than in letter fluency in AD,and category fluency is more likely to be impairedin MCI and/or to constitute a predictive factor fordementia. This is presumably due to breakdown in



semantic representations, since impairments in letterfluency are much less likely to be present in MCIor early AD, suggesting that these deficits are not aresult of executive or inhibitory dysfunction. Verbfluency appears to be more impaired than nounfluency, although this finding requires replication.

It is important to recall when interpreting theseresults that, while fluency measures may demon-strate impairment in preclinical AD, it does notfollow that such an impairment is predictive onlyof AD. For example, similar deficits in fluencytasks have been reported in preclinical AD andpreclinical vascular dementia (VaD; De Jager,Hogervorst, Combrinck, & Budge, 2003; Laukka,Jones, Small, Fratiglioni, & Bäckman, 2004). Incontrast, Duff Canning et al. (2004) found that let-ter fluency distinguished VaD patients, but not ADpatients, from normal controls, and Jones,Laukka, and Bäckman (2006) found that categorybut not letter fluency distinguished between pre-clinical AD and VaD individuals. Thus, categoryfluency may be more affected in AD and letter flu-ency in VaD, reflecting the semantic deficit seen inthe former group. Verbal fluency is also equiva-lently impaired in frontotemporal dementia andAD (Pasquier, 1999), indicating the executive com-ponent in this task. Depression has been shown toaffect letter but not semantic fluency, meaning thateven mild depression may reduce or eliminate dis-crepancies between letter and category fluency indementia (Ravdin, Katzen, Agrawal, & Relkin,2003).

A second important consideration in interpret-ing findings relating to neuropsychological per-formance in prodromal AD is that considerablevariability in performance is reported even in clini-cal cases of AD. For example, Fisher, Tierney,Rourke, and Szalai (2004) examined the perform-ance of two subgroups of probable AD patients onletter and category fluency tasks. Participants weregrouped into left-hemisphere AD (LAD) andright-hemisphere AD (RAD) subgroups on thebasis of their performance on the Boston NamingTest and Copy tasks. It was found that LAD andRAD participants performed similarly on letterfluency, while LAD participants performed morepoorly on category fluency and produced signifi-cantly more within-subclass clusters than did RADparticipants. Similar results were found by Shermanand Massman (1999). Given the heterogeneityfound amongst individuals diagnosed with proba-ble AD, it is to be expected that not all preclinicalAD individuals will manifest similar performances.Thus, while impaired performance on categoryfluency tasks may constitute a risk factor for con-version to dementia, it must be borne in mind that

a subset of those individuals who go on to developdementia will exhibit no impairment on semantictasks.

Naming

One well-documented symptom of Alzheimer’sdisease is word-finding difficulty (Bayles &Kaszniak, 1987; Bayles et al., 1992; Bowles et al.,1987; Fisher et al., 1999). Deficits in confrontationnaming typically occur early in the disease course(Cummings & Benson, 1989; Huff, 1990). As such,naming tests are widely used in clinical practice aswell as research settings.

One widely used naming test is the Boston Nam-ing Test (BNT; Kaplan, Goodglass, & Weintraub,1983), which comprises 60 items ranging from veryfrequent to very infrequent. This test predicts therate of cognitive decline in AD (Carswell, 1999;Rasmusson, Carson, Brookmeyer, Kawas, &Brandt 1996) and distinguishes between subgroupsof AD (J. K. Johnson, Head, Kim, Starr, &Cotman, 1999). In combination with the BlockDesign subtest of the Wechsler Intelligence Scalefor Children–Revised (Wechsler, 1974), it has beendemonstrated to be sensitive to asymmetric cogni-tive changes in early AD, where one hemisphere isaffected more than the other (Delis et al., 1992;Fujimori et al., 1998; Jacobs et al., 1995; Massmanet al., 1993). To facilitate testing of AD individu-als, whose limited attention span renders the full60-item version difficult to administer, Williamsand colleagues developed two 30-item versions ofthe BNT (Williams, Mack, & Henderson, 1989).These researchers found that the two versions wereequivalent, and that there was a significant correla-tion between each version and the full 60-item ver-sion, both in demented individuals and in healthysubjects. The same research group subsequentlyconstructed four 15-item versions and validatedthem in demented and nondemented elderly indi-viduals (Mack, Freed, Williams, & Henderson,1992).

A number of studies have examined the diagnos-tic and prognostic utility of tests of naming per-formance in MCI and AD, including, but notlimited to, the 15- and 60-item versions of theBNT. Summary statistics are provided in Table 1,and the findings are summarized in Appendix B.Differences have been found between healthy eld-erly controls and MCIs (Dwolatzky et al., 2003;Grundman et al., 2004; Petersen et al., 1999),between MCIs and ADs (Goldman et al., 2001;Petersen et al., 1999), and between incident ADand nondemented individuals up to two years priorto diagnosis (Blackwell et al., 2004; Nielsen et al.,



1999). Likewise, Bennett et al. (2002) found thatMCIs had lower baseline scores and declined morethan twice as rapidly as did healthy elderly controlson a composite score of semantic memory, includ-ing the BNT, and Storandt et al. (2002) reportedmore rapid rates of decline on the BNT as cogni-tive impairment progresses. Bozoki et al. (2001)found that the BNT discriminated best betweenindividuals with memory impairment who con-verted to AD and those who did not, although thiseffect missed significance.

The Graded Naming Test (GNT, McKenna &Warrington, 1983) is a 30-item naming test with itemsthat progressively decrease in familiarity. A numberof studies have suggested that it is sensitive to seman-tic deficits in AD and MCI (e.g., Blackwell et al.,2004; Dudas, Clague, Thompson, Graham, &Hodges, 2005; Thompson, Graham, Patterson, Saha-kian, & Hodges, 2002) and that it predicts incidentdementia (De Jager & Budge, 2005). Of particularinterest in the last study was the finding that deficitsin naming of famous faces was highly predictive ofconversion to AD in individuals with questionableAD (defined as complaints of declining episodicmemory in the absence of dementia). In a similarvein, Semenza, Mondini, Borgo, Pasini, and Sgara-mella (2003) demonstrated that tests of proper nameretrieval, both to description and in naming faces,were more sensitive to very mild AD (comparable toMCI) than other, longer batteries such as the Mini-Mental State Examination (MMSE, Folstein,Folstein, & McHugh, 1975) and the Milan OverallDementia Assessment (Brazzelli, Capitani, DellaSala, Spinnler, & Zuffi, 1994). This disproportionatedeficit for person naming in very mild or questionableAD clearly requires further exploration.

However, several studies have reported thatnaming tests do not predict incident dementia(Albert et al., 2001; Chen et al., 2001; Devanand,Folz, Gorlyn, Moeller, & Stern, 1997; Fox et al.,1997; Fox et al., 1998; Newman, Warrington,Kennedy, & Rossor, 1994; Ritchie et al., 2001;Schmidtke & Hermeneit, 2007; Small, Fratiglioni,Viitanen, Winblad, & Bäckman, 2000), that differ-ences are not seen until after diagnosis (Rubinet al., 1998), or that they are detectable at retest butnot at baseline (Guarch et al., 2004). In addition, ina recent study the 15-item BNT did not distinguishbetween MCI, normal controls, and individualsdiagnosed with major depressive disorder (Beinhoff,Hilbert, Bittner, Grön, & Riepe, 2005). These con-flicting results may be due in part to the differenttests used; shorter tests such as the 15-item BNT orthe naming subtest of the MMSE were less likely topredict incident dementia or differentiate betweensubject groups (e.g., of 12 studies reporting no

predictive or diagnostic value for the BNT, 6report using a shortened version). Likewise, smallsample sizes such as those used by Goldman et al.(2001) were less likely to yield significant differ-ences between subject groups. Finally, it is possiblethat only a subset of preclinical AD patientsexhibit a naming deficit. Hodges et al. (2006)report on the neuropsychological profile of 10MCI patients followed over at least six years. Theyfound that, while deficits in memory and categoryfluency occurred in most patients very early (in 7/10 patients at baseline and 8/10 at the end of thefirst year), naming deficits (assessed using the nam-ing task from the Cambridge semantic test battery;Hodges & Patterson, 1995) were more variable andunstable.

Whatmough et al. (2003) capitalized upon thewidely reported category effect in AD, wherebyAD individuals perform better on naming artifactsthan biological kinds (e.g., Daum, Riesch, Sartori,& Birbaumer, 1996; Fung et al., 2001; Silveri,Daniele, Giustolisi, & Gainotti, 1991). Theseauthors tested 56 ADs and 16 MCIs, as well as 40elderly controls, on a picture-naming task compris-ing 28 biological items (fruits, vegetables, or ani-mals) and 28 artifacts (tools, clothing, or furniture).Patients were then stratified into five groups on thebasis of their naming ability (the first three groupscomprising both MCI and AD individuals, and thebottom two groups only ADs). Results revealed thatthe category effect favoring artifacts increased withworsening anomia. These findings highlight (a) theheterogeneity of semantic memory impairment inAD (given that ADs spanned five levels of namingimpairment, and MCIs three); and (b) the relativelysteeper decline in naming biological kinds thanartifacts as semantic memory declines.

In sum, it appears that naming impairments dooccur in preclinical AD, although the diagnostic andprognostic utility of these tests is limited. Testa et al.(2004) assessed the diagnostic utility of the BNT rel-ative to other neuropsychological measures andfound that, while impaired performance on the BNTis associated with increased risk of AD, it impartedno additional diagnostic utility once delayed recallimpairments were included in the model.

Other standardized language tasks

Although confrontation naming and verbal flu-ency are the most frequently used standardizedlanguage tasks, there also exist a few studies inwhich MCI individuals’ performance on a broaderrange of standardized measures is reported. Thesestudies are summarized in Appendix C and are dis-cussed in more detail below.



The Pyramids and Palm Trees Test (Howard &Patterson, 1992). The Pyramids and Palm TreesTest (PPT) assesses semantic access via words orpictures. A few studies have reported MCI individ-uals’ performance on the different versions of thistask. Nestor, Fryer, Smielewski, and Hodges(2003) found that AD patients performed worsethan MCIs on the picture version of the PPT, whileMCIs did not differ from control participants. Incontrast, Dudas et al. (2005) report diminishedperformance on the PPT (picture version) in MCIand AD.

The Semantic Object Retrieval Test (Kraut et al.,2002). The Semantic Object Retrieval Test (SORT)assesses semantic association by requiring partici-pants to determine whether two objects are relatedthrough another (e.g., “desert” and “humps” arerelated through “camel”). Kraut et al. (2007) reportdata indicating that MCI individuals may be sub-divided on the basis of SORT performance, andthat performance on the SORT correlated withBNT performance; furthermore, in the semanti-cally impaired group, SORT performance wasassociated with declines in performance on tests offrontal lobe function. The authors suggest that theSORT may provide valuable diagnostic and prog-nostic information, although that remains to bedemonstrated.

The ECO battery. The Examen Cognitif par Ordi-nateur (ECO) battery used by Ritchie et al. (2001)includes a number of tests of language function,including verbal fluency and naming (discussedabove), as well as reaction time (RT) for word andsyntax comprehension. These authors found that RT(presented as a composite score of RT to syntax andto word comprehension) discriminated between nor-mal subjects and those with preclinical dementia 2years prior to diagnosis, independent of educationeffects.

The ACT system. Collie, Maruff, and Currie (2002)also examined RT for syntactic and semanticprocessing, as part of the Automated CognitiveTest system (ACT; Stollery, 1996). In the syntactictask, participants are shown sentences followed byexemplars and are required to verify whether thesentence are syntactically correct or not (e.g.,A follows B, AB = incorrect; A is followed by B,AB = correct). In the semantic task, participantsare provided with a semantic category and areasked to verify whether the word is an exemplarfrom the category or not (e.g., word = elm;category = tree). For the syntactic reasoningtask, accuracy discriminated significantly between

elderly controls and MCIs; however, RT did not,and neither accuracy nor RT discriminatedbetween the two groups for the semantic test.Given that syntactic deficits are not typicallyreported in MCI or early-stage AD, this findinglikely reflects deficits in domains other than syntaxproper.

Montreal Cognitive Assessment. Our group hasdeveloped a short (10-minute) neuropsychologicalbattery, the Montreal Cognitive Assessment(MoCA; Nasreddine et al., 2005), which assesses anumber of cognitive functions, including animalnaming, letter fluency, and sentence repetition.Both fluency and naming discriminated reliablybetween ADs, MCIs, and healthy elderly (itemanalyses available at http://www.mocatest.org/validation_study.html). Overall, the MoCA has90% sensitivity and 100% specificity for MCI.

Mindstreams battery. Dwolatzky et al. (2003) reporta new computerized cognitive assessment system(Mindstreams) designed to detect MCI in clinicalpractice. Verbal function is assessed using a nam-ing test and a rhyming test, whereby participantsare instructed to select the word that rhymes withthe name of the picture presented. Both thesemeasures were found to discriminate significantlybetween MCIs and healthy elderly subjects, as wellas between MCIs and ADs. These two tests of ver-bal function were then compared with traditionalverbal tests, including verbal fluency, BNT, andWechsler Adult Intelligence Scale–Third Edition(WAIS-III) similarities, in terms of their capacityto discriminate between MCIs and healthy elderly.The best traditional verbal test was found to be theControlled Oral Word Association–FS (COWA-FS;letter fluency), although this test did not discrimi-nate as well as the two verbal tests included in theMindstreams battery.

DemTect. DemTect (Kalbe et al., 2004) is a shorttest including five cognitive tasks, with a reportedsensitivity of 80% for MCI and 100% for AD. Thetest includes a word fluency task (supermarket),and in the validation study it was found to be oneof the two most sensitive tasks in terms of discrimi-nation between controls, MCIs, and ADs.

Vocabulary measures. Bennett et al. (2002) useda number of tests of language including categoryfluency, the 15-item BNT, the extended rangevocabulary test, and the National Adult ReadingTest (NART; Nelson, 1982). These scores werethen summarized to yield a measure of semanticmemory, which was lower at baseline and declined



more rapidly for MCIs than for healthy controlsubjects. Lambon Ralph et al. (2003), on the otherhand, found no difference between MCIs andhealthy controls on the NART. It should be notedthat the MCI group in the latter study was muchsmaller (n=17) than in the former (n=211), andthat criteria for amnestic MCI were more strictlyadhered to in the Lambon Ralph et al. (2003) study.

Cookie Theft Picture. Bschor et al. (2001) admin-istered the Boston Cookie Theft Picture test fromthe Boston Diagnostic Aphasia Examination(BDAE; Goodglass & Kaplan, 1983). In this task,participants are shown a picture where a number ofevents are occurring in a familiar setting (a kitchen)and are asked to “report all that happens in the pic-ture.” It was found that this task could distinguishhealthy controls and MCIs from ADs, but could notdifferentiate between controls and MCIs, norbetween the AD subgroups (see Appendix C fordetails of measures).

Complex Ideational Material. In the Complex Ide-ational Material subtest of the BDAE (Goodglass &Kaplan, 1983), participants hear statements orshort stories of increasing length and syntacticcomplexity and must then respond to questionsabout the material they have just heard. This testis considered to be a measure of executive function,but also relies on auditory comprehension. Bennettet al. (2002) created a summary measure of seman-tic memory on the basis of their participants’ per-formance on this task as well as vocabulary scores,category fluency, and naming, and found thatMCI individuals had a lower score at baselineand declined more rapidly than healthy controlsubjects.

Other tests of semantic processing. Lambon Ralphet al. (2003) included a number of additional testsof semantic processing in their study, includingword–picture matching, picture sorting by feature,naming to verbal description, and semantic featurequestions. MCI individuals could not be distin-guished from normal control subjects on thesemeasures; impairments began to appear at thepoint at which individuals developed mild demen-tia. Hodges and Patterson (1995) also includednaming to verbal description, answering of seman-tic feature questions, and word–picture matching.They found that patients with minimal AD(MMSE > 23) showed deficits in the majority ofthese tests, suggesting that semantic memory isimpaired very early in the disease course in manypatients, although it was found that episodic mem-ory was a more accurate marker of AD.

Syntactic processing

While syntactic impairments are not typically seenin AD, certain studies have included measures ofsyntactic comprehension in MCI, typically theToken Test (De Renzi & Vignolo, 1962) or the Testfor the Reception of Grammar (TROG; Bishop,1989). Of all semantic and language tests, LambonRalph et al. (2003) found differences between MCIpatients and control subjects only on the TokenTest. This finding was taken to indicate impairedworking memory or attentional-executive process-ing, rather than impaired syntactic processing,since MCI individuals showed no impairment onthe TROG; impairments on this task only appearedonce the individuals were at the DAT (mild demen-tia of the Alzheimer’s type) stage. Hodges et al.(2006) also included the TROG as part of their bat-tery and found no significant effects. De Jageret al. (2003) evaluated the sensitivity and specificityof a broad variety of neuropsychological tests forMCI, as well as AD and vascular cognitive impair-ment. These tests included the Token Test (short-ened version; Lezak, 1995), which distinguishedbetween MCI individuals and those suffering fromcerebrovascular disease or AD. However, no differ-ence was seen in the performance of control andMCI participants. Ribeiro et al. (2006), on the otherhand, found significant impairments on a modified(Portuguese) version of the Token Test: A total of33.7% of their MCI participants exhibited animpairment on this task (compared to only 30.2%on semantic fluency). In addition, as mentionedabove, Collie et al. (2002) report deficits in MCI ona syntactic reasoning task.

In sum, the results of standardized languagetests suggest that MCI individuals often manifestdeficits in semantic processing, although this is notinvariably the case. Episodic memory appears tobe affected before other cognitive domains,although those individuals who manifest impair-ments in one or more cognitive domains in addi-tion to memory are more likely to convert to AD(Alexopoulos et al., 2006; Bozoki et al., 2001;Sacuiu et al., 2005). As such, tools for detection ofsubtle deficits in the lexical-semantic domain are ofparticular interest, as these would allow greaterprognostic sensitivity for AD. We now turn to anoverview of the literature on MCI and languageusing nonstandardized measures.

NONSTANDARDIZED LANGUAGE TESTS

While the majority of research on language func-tion that has been conducted with MCI individuals



has focused on standardized tests of language func-tion, there exists nonetheless a small body of litera-ture reporting on various aspects of languageperformance in this group using other, nonstand-ardized, measures. These studies are discussedbelow, subdivided according to modality (receptivevs. expressive). Since MCI is a newly defined syn-drome, such research is relatively scarce. We there-fore include findings relating to minimal AD(typically defined as CDR of 0.5 and/or MMSE > 23),which mimics the deficits seen in MCI.

Receptive language

Alterations in receptive language processing havebeen reported at a number of levels in MCI. Webegin with a discussion of studies at the single-word level, then moving to sentence and finallydiscourse-level processing.

Single-word identification

At the perceptual level, Massoud, Chertkow,Whitehead, Overbury, and Bergman (2002) dem-onstrated that word-reading threshold (WRT) is apotentially useful tool for discriminating MCI indi-viduals who will progress to AD. These authorsconducted a study with 13 AD participants, 13MCI participants, and 12 healthy elderly controls,in which participants read aloud backward- andforward-masked words presented at increasinglylong intervals. WRT was defined as the targetduration at which 50% of words could be read, anda WRT threshold of 85 ms was found to success-fully distinguish 10 of 13 ADs and 11 of 12 healthyelderly controls. This compares favorably with aprevious study of letter identification thresholdthat allowed correct classification of only 59% ofAD patients (Mendola, Cronin-Golumb, Corkin,& Growdon, 1995). Furthermore, while MCI indi-viduals could not be distinguished from the othergroups on the basis of this test, the 4 MCIs whosethresholds were above 85 ms had progressed to ADat two-year follow-up. This study indicates thatimpairments in single-word processing are ofpotential prognostic significance for MCI.

This issue was further investigated byVandenbulcke, Peeters, Dupont, Van Heckeand Vandenberghe (2007). They report an func-tional magnetic resonance imaging (fMRI) study inwhich MCI individuals and healthy elderly controlsperformed a semantic-associative task with eitherwords or pictures. It was found that activation inthe lower bank of the posterior third of the leftsuperior temporal sulcus (STS) indexed word-specificprocessing in elderly controls. MCI individuals, on

the other hand, manifested a significant reductionin this activation. Participants also completed aword identification task similar to that used byMassoud et al. (2002), in which they were requiredto identify forward- and backward-masked pic-tures and words presented at increasing intervals(30–800 ms). Overall, the slope of time–accuracyfunction was steeper for controls than MCIs in theword but not the picture identification task, suggest-ing that controls are quicker to generate associa-tions to the stimulus. Furthermore, there was asignificant correlation between slope and fMRIresponse amplitude in the STS. The authors suggestthat the STS may constitute the neural substrate forthe deficit in word identification reported byMassoud et al. (2002) and postulate that dedifferen-tiation of the connections between orthographicword forms and their meaning may underlie theslowing in identification of written words in MCI.

Lexical-semantic processing

While there exists plentiful evidence of semanticdeficits in MCI, only a few studies examine lexical-semantic processing in MCI using nonstandardizedtests. Puregger, Walla, Deecke, and Dal-Bianco(2003) report a magnetoencephalographic (MEG)study in which MCI subjects and healthy age-matched controls were asked to encode wordseither semantically (animate or inanimate) or non-semantically (presence or absence of letter “s”) andthen identify already-seen items. Behavioral meas-ures showed no difference between the two groups,but differences were seen in the MEG signal whileencoding was taking place: MCIs showed greateractivation in the shallow (nonsemantic) encodingcondition over left frontal and temporal sensors250–450 ms following stimulus onset. No sucheffect was seen in control subjects. This finding wasinterpreted as reflecting additional neural activa-tion required for shallow encoding, to compensatefor neurodegeneration.

Similarly, Olichney et al. (2002) examined elec-trophysiological response in MCI individuals(n=14) and healthy elderly controls (n=14) to sin-gle words during a categorization task. Subjectswere presented category statements (e.g., “a break-fast food”) and then congruous items (e.g.,“pancake”) or length- and frequency-matchedincongruous words. They found that MCI individ-uals manifested a delayed N400, a negative peak inthe EEG waveform approximately 400 ms afterstimulus onset, which is taken to reflect semanticintegration processes. Furthermore, control sub-jects manifested a late positive component to newwords, which was significantly diminished when a



word was repeated. This repetition effect was muchweaker for MCI participants and was almostentirely accounted for by the 7 MCI subjects whodid not subsequently convert to AD. That is, theabsence of a repetition effect appears to predictsubsequent conversion from MCI to AD. Taylorand Olichney (2007) report follow-up analyses ofthis cohort of MCI individuals. Converters mani-fested a delayed and spatially circumscribed N400repetition effect at baseline, and this effect wasabsent altogether in the group averages after oneyear. Furthermore, the baseline P600 repetitioneffect accurately discriminated 11 of 13 MCI indi-viduals who converted to AD over the next threeyears, suggesting that these effects may be clini-cally useful in prognosis of MCI.

Davie et al. (2004) report a study examiningMCI individuals’ sensitivity to expectancy viola-tions. These researchers used a semantic primingparadigm, where subjects decided whether visuallypresented word pairs were related or not. Partici-pants included healthy younger (n=80) and older(n=22) control subjects, as well as participants diag-nosed with MCI (n=10). An expectancy bias wascreated by manipulating the proportion of category-related (apple–fruit) and coordinate-related pairs.When a high proportion (80%) of category pairs waspresented, both control and MCI groups showedan expectancy bias, but MCI individuals showed amuch greater cost for unexpected targets.

Taler and Jarema (2006) report a study in whichgroups of healthy elderly controls (n=11), MCI(n=8), and AD (n=8) individuals were asked toperform lexical decisions on nouns of differing cat-egories: mass nouns such as cheese, count nounssuch as table, and nouns that are mass/countambiguous, such as chicken. Healthy older adultsmanifested faster response times to ambiguousnouns than to mass or count nouns, while neitherMCI nor AD participants showed such an advan-tage for ambiguous nouns. This was interpreted asreflecting an impaired semantic network in thesepopulations. These findings are consistent withprevious research by the same authors (Taler &Jarema, 2004), in which MCI and AD individualswere asked to distinguish between mass and countreadings of mass/count ambiguous items such as“chicken.” In this study, participants were pre-sented with pictures representing the mass andcount readings of each noun and were asked toeither “Point to the picture of chicken” or “Pointto the picture of a chicken.” While a minority ofpatients from both MCI and AD groups manifestedcontrol-like performance, most patients wereimpaired on this task. Furthermore, performancedid not differ significantly across the two groups.

One important distinction in semantic process-ing is that between intentional and automaticprocessing: Word-naming and verbal fluency tasksrequire intentional processing, while tasks such aslexical decision and word identification tap moreautomatic processing. In AD, impairments areseen in both types of processing, and the order inwhich these impairments appear is not clear.Recent research indicates that MCI individuals’performance on intentional access tasks (picturenaming and semantic probes) is impaired but per-formance on tasks tapping automatic access (lexi-cal decision and semantic priming) is not (Duong,Whitehead, Hanratty, & Chertkow, 2006). Impair-ments were also seen in performance on Strooptasks, and the authors suggest that impairments inlexical-semantic tasks may be attributable to defi-cits in inhibition during semantic search. Theauthors acknowledge that task difficulty may alsoplay a role, although it appears that this factorcannot fully account for the findings. These find-ings are in contrast to those reported above, whichsuggest deficits in automatic as well as intentionalprocessing. However, it is possible that the tasksused by Duong et al. (2006) did not tap a suffi-ciently subtle aspect of automatic lexical-semanticprocessing. For example, Taler and Jarema (2006)found that MCI and AD individuals did not showan advantage for lexical items with multiple relatedsenses, the so-called “ambiguity advantage”(Rubinstein, Garfield, & Millikan, 1970), whileolder adults did. The priming task used by Duonget al. (2006) relied upon associative strengthbetween prime and target and thus may not havebeen sensitive to subtle alterations in automaticlexical-semantic processing in MCI participants.

While most studies of single-word processing inAD and MCI have focused on nouns, Grossmanand colleagues have conducted a number of studiesexamining verb processing in AD. These investiga-tors have found different patterns in brain activa-tion in AD patients versus healthy controls inprocessing of verbs of motion and cognition(Grossman et al., 2003a). In addition, they showimpairment in identifying semantic relationsamong verbs (Grossman, Mickanin, Onishi, &Hughes, 1996). In combination with the findingthat verb fluency is disproportionately impaired inMCI (Östberg et al., 2005), these findings indicatethat further studies of deficits in verb processingmay be fruitful in terms of characterizing the lan-guage impairment in prodromal AD.

In sum, while studies of lexical-semantic process-ing in MCI are scarce, they appear to hold promisefor better characterization of the neuropsychologicalprofile of MCI individuals. Qualitative alterations



are seen in a number of tasks, including single-word recognition, as well as in terms of primingand expectancy biases. Such alterations may beattributable to inhibition deficits, whereby MCIindividuals have difficulty inhibiting informationwhile performing semantic search; that is, thelexical-semantic impairments observed in MCImay be due to an interaction between executivefunction and language (Duong et al., 2006). Such aclaim is consistent with the finding that MCI andpreclinical AD individuals tend to exhibit greaterimpairments in category fluency, which comprisesa substantial executive component, than on nam-ing tasks, which place lesser demands on executivefunction.

Sentence and discourse level

Croot, Hodges, and Patterson (1999) foundeffects of AD on sentence comprehension, evenwhen patients were at the minimal stage of thedisease, although these effects were variableacross individuals. Chapman et al. (2002) assesseddetail-level and gist-level discourse processing inMCI individuals (n=20), patients with mild AD(MMSE ≥ 16; CDR ≤ 1; n=24), and cognitivelynormal elderly control subjects (n=25). Participantswere read a 578-word biographical narrative andwere provided with a written copy of the text sothat they could follow along. They were thengiven 5 minutes to review the written text, whichwas removed before they were asked questionsprobing detail- and gist-level processing. Partici-pants were asked to summarize the text, providethe main idea in one sentence, and construct a les-son that could be learned from the story. Recog-nition and recall of specific details of the text werethen tested. These authors found that AD andMCI individuals showed impairments in gist-levelprocessing (summary, main idea, and lesson) rela-tive to healthy elderly controls. A more detailedexamination of individual participants’ perform-ance revealed that 13 of 20 MCI patients were inthe impaired range in performance on gist-leveltasks. Detail-level processing was also impaired inboth groups and was relatively more impaired inAD than in MCI. The authors conclude thatdetail-level processing is impaired earlier in thedisease course than is gist-level processing.Hudon et al. (2006) likewise examined memoryfor gist-level and detail information in MCI andAD. These researchers found an increase in falserecognition of gist-level information in AD butnot MCI. In recall, however, both MCI and ADparticipants exhibited deficits both for gist-leveland detail information.

Language production

Although limited research has been conducted onlanguage production in MCI, the likelihood thatalterations occur in spontaneous language produc-tion has been highlighted by a recent study indicat-ing reductions in semantic skills and sophisticationof vocabulary in Iris Murdoch’s last novel, pub-lished a year before her diagnosis with AD(Garrard, Maloney, Hodges, & Patterson, 2005).Similarly, subtle language alterations were revealedin an analysis of the speeches given by RonaldReagan in his reelection campaign for the US pres-idency, some 10 years prior to his diagnosis withAD (Venneri, Forbes-McKay, & Shanks, 2005).These cases suggest that spontaneous languagemay be among the skills altered very early in AD.In the present section, we report studies examininglanguage production in both spoken and writtenmodalities.

Production of definitions

Hodges, Patterson, Graham, and Dawson(1996) examined the performance of control partic-ipants and minimal, mild, and moderate ADpatients on naming and generation of definitionsfor a set of nouns and found that the quality of def-inition produced differed between groups. Specifi-cally, all ADs produced definitions with lesscorrect information that sometimes failed to con-vey the core concept. For the minimal and mildAD groups, this was correlated with inability toname the object.

Spontaneous speech

AD individuals produce semantically impover-ished discourse that is lacking in coherence,although the syntax is relatively preserved (Kemperet al., 1993). While studies of spontaneous speechin MCI are virtually nonexistent (although seeBschor et al., 2001, discussed above), someresearch has examined spontaneous languageproduction in minimal AD, which is comparable toMCI.

Forbes, Venneri, and Shanks (2002) assessed thespontaneous speech of patients with minimal(n=11) and mild (n=11) AD, as well as age- andeducation-matched controls. These researchersused a simple and a complex picture descriptiontask and found that, while both tasks distinguishedAD patients from controls, only the complex pic-ture description task was able to differentiatebetween minimal AD patients and healthy controlsubjects. Significant differences were seen in measuresof production of semantic paraphasias, word-finding



delays, error monitoring, and information con-veyed. Forbes-McKay and Venneri (2005) recentlyconducted a study aiming to collect normative datafor AD individuals in a picture-description task, aswell as to determine whether normal cognitivedecline can be differentiated from pathologicalalterations on the basis of spontaneous languageproduction. In this study, 240 healthy participantsaged between 18 and 90 years, as well as minimal(n=10), mild (n=10), and moderate (n=10) ADpatients were asked to describe, both orally and inwriting, two simple line drawings (the CookieTheft Picture, Goodglass & Kaplan, 1983; and theTripping Woman Picture, Semenza & Cipolotti,1989) and two complex drawings (the TrafficChaos Picture and the Bus Stop Picture, unpub-lished). It was found that measures of informationcontent, pictorial themes, word-finding delays, andthe response given to these delays discriminatedbest between healthy elderly individuals and ADpatients, and the complex picture description taskwas sensitive even to early stages of AD. The pat-tern of errors seen in these studies points to abreakdown in lexical-semantic functioning in theseindividuals; no such breakdown was seen inhealthy elderly subjects. These findings are thusconsistent with the findings reported for othermeasures of semantic functioning, such as categoryfluency.

Writing

It is well established that writing difficultiesoccur in AD, and in fact these difficulties were firstreported by Alzheimer himself in describing hispatient Augusta D. (Alzheimer, 1907; see Stelz-mann, Schnitzlein, & Murtagh, 1995). At the lin-guistic level, AD individuals produce texts that areshorter than those produced by controls (Croisile,Carmoi, Adeleine, & Trillet, 1995; Croisile et al.,1996; Henderson, Buckwalter, Sobel, Freed, &Diz, 1992; Horner, Heyman, Dawson, & Rogers,1988; Neils, Boller, Gerdeman, & Cole, 1989) andcontain less relevant information (Croisile et al.,1995, 1996; Henderson et al., 1992; Kemper et al.,1993). Sentences are less syntactically complexthan those produced by controls (Croisile et al.,1996; Kemper et al., 1993), although AD patientsand control subjects produce a comparablenumber of grammatical errors (Croisile et al.,1996; Horner et al., 1988; Neils et al., 1989). Thatis, syntactic structures are simplified but coherent(Kemper et al., 1993). A high number of semanticsubstitutions or intrusions and misspellings arealso seen (Croisile et al., 1996; Glosser & Kaplan,1989; Henderson et al., 1992; Horner et al., 1988;

Neils et al., 1989). In sum, it can be concluded thatgreater impairments are seen at the lexical-seman-tic than at the syntactic level (Croisile, 1999).Many AD patients do not show any impairment inspelling (Croisile, 1999; Luzzatti, Laiacona, &Agazzi, 2003). However, the most common patternappears to be a surface dysgraphia, wherebywriting of irregular or ambiguous words via anorthographic output lexicon is more impaired thanwriting of pronounceable words or nonwordsthrough grapheme–phoneme correspondence rules(Croisile, 1999). Silveri, Corda, and di Nardo(2007) found that central orthographic (i.e.,lexical-semantic) errors were more prevalent in theearly stages of AD, and peripheral errors (e.g.,omission of strokes) increased as the disease pro-gressed. They suggest that dysgraphia in AD is theresult of a reduction of general cognitive resourcesin AD, rather than disorders of specific subcompo-nents of spelling.

Despite these findings, systematic studies ofwriting performance as a diagnostic or prognosticmarker for AD are scarce. One large-scale studythat is of particular interest is the Nun Study con-ducted by Snowdon and colleagues. Theseresearchers have demonstrated that text-level writ-ing abilities in early adulthood are a strong predic-tor of subsequent onset of dementia (Snowdon et al.,1996) or mild cognitive impairments (Riley, Snow-don, Desrosiers, & Markesberry, 2005) decadeslater. These studies examined the relationshipbetween autobiographies written by nuns twoyears prior to formally joining a congregation(average age=22 years) and their cognitive func-tion several decades later (average age=80 years).The texts were measured in terms of idea density,defined as the average number of ideas expressedper 10 words, which corresponds to elementarypropositions (verb, adjective, adverb, or preposi-tional phrase), and complex propositions (statingor inferring causal, temporal, or other relation-ships between ideas). Participants were then classi-fied as having low idea density (bottom third) orhigh idea density. It was found that idea densitycorrelated significantly with late-life cognitivefunction, as well as late-life scores on standardizedmeasures of cognitive function, including the BNTand verbal fluency. Given these intriguing findings,it seems likely that writing ability constitutes animportant potential diagnostic and prognostic toolfor AD and MCI. However, it should be noted thatthis may reflect a discourse-level deficit rather thana deficit in writing per se, since narratives were nottested in the oral modality.

There also exist a few studies examining writingabilities in minimal AD. Werner, Rosenblum,



Bar-On, Heinik, and Korczyn (2006) report alter-ations in kinematic measures of handwriting, suchas time taken to complete writing tasks and pres-sure on the writing surface, which discriminatebetween healthy elderly adults and MCI and mildAD individuals better than the MMSE. Forbes,Shanks, and Venneri (2004) had minimal(MMSE ≥ 25), mild (MMSE 19–24), and moderate(MMSE 12–18) AD individuals describe in writingtwo simple line drawings (the Cookie Theft Picture,Goodglass & Kaplan, 1983; and the TrippingWoman Picture, Semenza & Cipolotti, 1989) andtwo complex drawings (the Traffic Chaos Pictureand the Bus Stop Picture, unpublished). Outputwas assessed according to syntactic complexity,number of paraphasias, information content, com-plexity (writing in cursive), and the proportion ofwords containing legible letters, stroke errors, orallographic errors (inappropriate mixing of upperand lower case). Consistent with previous litera-ture, mild and moderate AD individuals producedwritten narratives with multiple error types (inco-herent/indefinite phrases, semantic and graphemicparaphasias, and inability to abstract and describeall pictorial themes). Patients with minimal AD,however, were distinguishable from control sub-jects only on semantic measures: They manifestedlower information content and capacity to abstractand describe pictorial themes. This is consistentwith the claim that these individuals suffer from acentral semantic impairment even in very earlystages of the disease, as suggested by MCI patients’performance on semantic tasks discussed throughoutthe present paper.

CONCLUSIONS

Characterizing the language impairment in MCI

The findings reviewed here point toward the pres-ence of linguistic deficits in MCI that parallel thosefound in AD. These include deficits in verbal flu-ency, especially category fluency, and in confronta-tion naming, as well as in a variety of other lessstudied language tasks including RT for languagecomprehension (Ritchie et al., 2001), accuracy insyntactic reasoning (Collie et al., 2002), and nam-ing a rhyming word (Dwolatzky et al., 2003).Alterations in performance on a variety of othersemantic tests have also been reported (e.g., inMCI: lexical decision, Taler & Jarema, 2006;semantic categorization, Olichney et al., 2002;semantic encoding, Puregger et al., 2003; semanticpriming, Davie et al., 2004; in minimal AD: namingto verbal description and semantic feature questions,

Hodges & Patterson, 1995). Alterations in produc-tive and receptive discourse-level processing havealso been reported in MCI and minimal AD(Chapman et al., 2002; Forbes et al., 2004; Forbeset al., 2002; Forbes-McKay & Venneri, 2005; Gar-rard et al., 2005; Hudon et al., 2006; Riley et al.,2005; Snowdon et al., 1996). However, these altera-tions appear earlier under more difficult con-ditions: A simple picture-description task, such asthe Cookie Theft Picture, is less likely to revealalterations in MCI or minimal AD (Bschor et al,2001; Forbes-McKay & Venneri, 2005). Likewise,impairment in purer tests of syntax, such as theToken Test and the TROG, are less consistent:Lambon Ralph et al. (2003) and Ribeiro et al.(2006) report impaired performance on the former,whereas De Jager et al. (2003) do not, and LambonRalph et al.’s (2003) and Hodges et al.’s (2006)MCI participants manifested intact performanceon the latter. In sum, it appears that linguisticimpairments in MCI are most likely located at thesemantic level, as is seen in the early stages of AD.Syntactic processing is typically reported to bemore or less intact (although cf. Ribeiro et al.,2006).

Of particular interest are findings suggestingthat timed tests are especially sensitive to thedeclines seen in MCI. Massoud et al. (2002) reportthat word-reading threshold may be useful in dis-criminating MCIs who will convert to AD; simi-larly, temporally precise methodologies, such aslexical decision (Taler & Jarema, 2006), event-related potentials (ERPs; Olichney et al., 2002),and MEG (Puregger et al., 2003), appear to distin-guish well between MCI and healthy controls andeven predict conversion to AD (Olichney et al.,2002). To a lesser extent, the reported deficits incategory fluency tasks, which impose a time limiton responses, are also sensitive to MCI and predictconversion to AD, although it should be noted thatstudies that adhere strictly to the diagnostic criteriafor amnestic MCI, which exclude individualswith deficits in domains other than memory(e.g., Karrasch et al., 2005; Lambon Ralph et al.,2003) are less likely to produce significant results.Furthermore, these tests have been reported tohave diagnostic utility in large-scale epidemiologicalstudies; their utility on an individual-by-individualbasis is less clear.

One question that remains is the locus of thesemantic deficit in MCI and AD. While muchresearch has centered on degradation of semanticknowledge in these populations, recent researchhas suggested that these deficits may be due at leastin part to deficits in executive functions that affectsemantic search or categorization. For example,



Grossman et al. (2003b) examined rule-based andsimilarity-based categorization in AD and FTDand found deficits in rule-based but not similarity-based categorization in both AD and FTD. Theyargue that deficits in executive function underliethese declines in rule-based processing in AD.Duong et al. (2006) similarly conclude that seman-tic impairments in MCI may be due to inhibitorydeficits affecting semantic search.

Distinguishing prodromal AD from other dementias

One crucial issue is the distinction between prodro-mal phases of AD and other types of dementia. It hasbeen suggested (Petersen, 2003) that MCI may evolveto AD, VaD, frontotemporal dementia (FTD), Lewybody dementia (LBD), or primary progressive apha-sia (PPA). Any tool designed to detect prodromalAD must provide sufficient specificity in addition tosensitivity. When considering tools to detect earlylanguage impairments, care must be taken to excludeother dementias.

AD versus vascular dementia

A number of studies indicate similar declines insemantic memory in AD and VaD (Bentham,Jones, & Hodges, 1997; De Jager et al., 2003;Laukka et al., 2004; Vuorinen, Laine, & Rinne,2000). For example, Bentham et al. (1997) reportthat VaD and AD individuals perform similarly oncategory fluency, naming, picture sorting, and gen-eration of definitions, showing impairment relativeto healthy elderly adults, while neither groupshowed impairments relative to controls on word–picture matching. Vuorinen et al. (2000) foundimpairments in both groups on complex auditorycomprehension and picture-naming tasks, but nor-mal performance on oral reading and single-wordrepetition.

However, differences have been reported inlanguage performance in VaD and AD. N. L.Graham et al. (2004) report more impaired seman-tic memory in VaD than AD on a variety of tasks:VaD patients exhibited impairments on categoryfluency, the Camel and Cactus test (Bozeat, LambonRalph, Patterson, Garrard, & Hodges, 2000), con-crete and abstract word synonym test, and theGNT, while AD patients showed impairments onlyon category fluency and the GNT. VaD patientshave also been found to perform better on tasks ofconfrontation naming than AD patients, and showbetter preserved lexical-semantic abilities, whiledeclines in syntactic abilities are seen in VaD butnot AD (Desmond, 2004; Pasquier, 1999).

While more errors are seen in naming tasks inAD than in VaD (Almkvist, 1994), the pattern oferrors (visuoperceptual, semantic, or phonemic)has been reported to be similar in the two groups,although AD patients commit more superordinateerrors than VaD patients (Lukatela, Malloy,Jenkins, & Cohen, 1998). More perseveration isseen in VaD than in AD (Desmond, 2004), andTraykov et al. (2002) report higher rates of perse-verative errors in AD than in early-stage VaD in asemantic fluency task (using the categories of ani-mals, fruits, vegetables).

Recently, it has been reported that languageimpairments may appear in the prodromal phaseof VaD (Laukka et al., 2004; although cf. Joneset al., 2006). Likewise, a recent study (Sacuiu et al.,2005) had a large pool of nondemented elderlyindividuals complete a number of tasks, includinga language task in which they were required toidentify synonyms among five alternatives, as wellas tasks assessing memory and visuospatial andexecutive function. Memory impairment in combi-nation with impairment in any other domain bestpredicted incident dementia, prodromal AD wasmost related to impairments in memory and execu-tive function, and the best predictor of VaD wasimpairment in language function according toinformants, in combination with a global patternof deficits. Frisoni, Galluzzi, Bresciani, Zanetti,and Geroldi (2002) report superior performance oncategory and letter fluency in amnestic MCI rela-tive to MCI with subcortical vascular features,while both populations performed similarly on theToken Test. More recently, letter fluency has beenfound to be among the most accurate scales to dis-tinguish between amnestic MCI and MCI withsubcortical vascular features (Galluzzi, Sheu,Zanetti, & Frisoni, 2005). In contrast, Loewensteinet al. (2006) found similarly impaired performancein amnestic and vascular MCI on both letter andcategory fluency. Luis et al. (2004) likewise reportsimilar performance in amnestic and vascular MCIon letter fluency, BNT, and Wechsler Adult Intelli-gence Scale–Revised (WAIS–R) Similarities andVocabulary. These findings highlight both the needto exclude other syndromes such as VaD whenconsidering the prognostic value of tests of lan-guage function and the difficulty in doing so.

AD versus frontotemporal dementia, semantic dementia, and primary progressive aphasia

The term frontotemporal dementia (FTD) refersto a group of degenerative dementias affecting thefrontal or temporal lobes. A variety of terms are



used to refer to different subtypes of FTD, includ-ing Pick’s disease, dementia of the frontal type,frontal lobe dementia of the non-Alzheimer’s type,frontotemporal lobar degeneration, semanticdementia (SD), progressive nonfluent aphasia, andprimary progressive aphasia (PPA; Hutchinson &Mathias, 2007).

Of particular relevance with respect to languagetests are dementias that specifically affect languagefunction, including PPA and SD. There exist a fewstudies comparing language performance in thesepopulations and examining the predictive value ofneuropsychological tests in dementia diagnosis.Performance on language tasks has been found tobe equivalent (Cosentino, Chute, Libon, Moore, &Grossman, 2006; Gregory, Orrell, Sahakian, &Hodges, 1997; Pachana, Boone, Miller, Cummings,& Berman, 1996) or lower (Diehl et al., 2005; Perry& Hodges, 2005) in FTD than in AD. Cosentinoet al. (2006) had AD, behavioral FTD, and SDparticipants complete the PPT, the 15-item BNT,the COWA-FS and the verb similarity task (Price &Grossman, 2005), which is designed to resemblethe PPT but utilizing verbs rather than nouns. Nodifference was seen between the three groups onany of these measures. Diehl et al. (2005)compared performance on the CERAD-NAB(Consortium to Establish a Registry for Alzhe-imer’s Disease—Neuropsychological AssessmentBattery) subtests by AD, FTD, and SD patients.Patients with FTD were more impaired than ADpatients in animal fluency, and patients with SDwere more impaired than both FTD and ADpatients on animal fluency and the BNT. Perri et al.(2005) found equivalent BNT performance butlower phonological fluency performance in FTDthan in AD. In a longitudinal study of semanticmemory in SD, AD, progressive nonfluent apha-sia (PNFA), frontal variant frontotemporaldementia (fvFTD), and posterior cortical atro-phy (PCA), Rogers, Ivanoiu, Patterson, andHodges (2006) report a performance pattern indi-cating amodal semantic impairment in SD and asimilar but less impaired performance in AD. InPNFA, fvFTD, and PCA, semantic impairmentswere found, but appeared to be secondary toother factors.

In addition, language has been found to declinefaster in PPA and in the behavioral variant of FTDthan in AD (Blair, Marczinski, Davis-Faroque, &Kertesz, 2007), as assessed by the Western AphasiaBattery (WAB; Kertesz, 1982). Similarly, Krameret al. (2003) found greater impairments on con-frontation naming in SD than in AD or FTDpatients but comparably diminished performanceon animal fluency. B. T. Gold et al. (2005) report

that individuals diagnosed with SD manifestimpairments in naming but not picture recognitionmemory, while AD individuals show the oppositepattern.

Hodges et al. (1999) utilized a comprehensive setof semantic and language tests, in addition to teststapping other aspects of cognitive function, in anattempt to distinguish early AD from the frontallobe variant of FTD as well as SD (referred to asthe temporal variant of FTD). Participants com-pleted the National Adult Reading Test (NART,Nelson, 1982), letter fluency (FAS), the Pyramidsand Palms test (PPT), and a semantic test batterycomprising six subtests: category fluency for sixmain categories and two lower order categories(breeds of dog and types of boat); naming of linedrawings; naming to verbal description; semanticfeature questions (e.g., “What do we call the largeAfrican animal with a curved horn on its head?”);picture sorting; and word–picture matching. Par-ticipants also completed tests assessing auditory-verbal short-term memory, episodic memory, andvisuospatial abilities. AD patients exhibited a pre-dominant deficit in episodic memory, althoughdeclines were also seen in semantic memory (cate-gory fluency and naming to verbal descriptions)and visuospatial skills. SD participants exhibitedprofound deficits on all semantic tasks, as well asthe NART (reflecting a disrupted ability to readirregular words). Finally, FTD (frontal variant)participants showed deficits in episodic memoryand category fluency, similar to the AD group, butnormal semantic memory.

Vandenberghe et al. (2005) report a study exam-ining semantic priming in PPA, MCI, and probableAD. Participants named pictures that were precededby a word that was the picture name, a semanticallyrelated noun, a semantically unrelated noun, or apseudoword. While healthy controls and MCI andAD participants were faster to name the pictureafter a related than after an unrelated prime, thereverse pattern was obtained in PPA. The authorssuggest that this “semantic interference effect” maydistinguish between PPA and probable AD individ-uals. Similarly, Price and Grossman (2005) exam-ined detection time for words following violations ofthematic role assignment or transitivity in AD andFTD. Control participants took longer to detectitems preceded by either type of violation, FTDpatients were insensitive to both types of violation,and AD patients were slowed by thematic role butnot transitivity violations. The authors interpretthese findings in terms of a broader degradation ofverb representations in FTD than in AD.

Hutchinson and Mathias (2007) recently con-ducted a meta-analysis of neuropsychological



deficits in AD and FTD, including a large numberof language tests. The language tests that best dis-criminated between the two, with FTD individualsmanifesting greater impairment than AD individuals,were the GNT, word–picture matching, WAB-spontaneous speech, WAB-comprehension, PPT-words, PPT-pictures, and picture-naming tasks(effect size >0.80 in all cases, small overlap, andhigh degree of accuracy in distinguishing the twogroups, as measured by the 95% confidence interval).

These findings point the way to possible meth-ods for distinguishing the different dementias atan early stage. A profound semantic deficit, incombination with relatively intact visuospatialabilities and episodic memory is a marker of SD;AD patients, in contrast, show impairments inepisodic memory and milder semantic deficits. Itshould be noted, however, that not all studieshave found differing performance in verbal epi-sodic memory in AD and SD (e.g., Scahill,Hodges, & Graham, 2005). In addition, perform-ance decrements in the NART have beenreported in SD but not in AD (Hodges et al.,1999).

Of particular interest are recent studies examin-ing semantic deficits at a more precise level thanstandardized semantic tasks such as category flu-ency. For example, Vandenberghe et al. (2005)posit the “semantic interference effect” as a poten-tial distinguishing marker between PPA and AD,and Price and Grossman (2005) found differencesin sensitivity to verb agreement violations in FTDand AD. Such fine-grained distinctions betweendiffering dementias are likely to prove fruitful inearly diagnosis.

Recently, de Mendonça, Ribeiro, Guerreiro, andGarcia (2004) proposed a set of criteria to identifyfrontotemporal MCI. These include symptoms offrontotemporal dysfunction, behavioral and affec-tive symptoms, speech disturbance, and alterationin at least one test that reflects executive function.In addition, patients should have intact activitiesof daily living and a computed tomography (CT)or MRI scan that is either normal or shows fronto-temporal atrophy. A total of 7 patients meetingthese criteria were tested on a variety of neuropsy-chological tests, and the majority did not showimpairment in naming (5/7) or language compre-hension (4/7). These findings suggest that lan-guage tests likely differentiate between prodromalAD and FTD, although it should be noted thatthe criteria used by de Mendonça et al. (2004) tar-get the behavioral (frontal) variant of FTD andprobably exclude cases of prodromal SD andPPA, in which language/semantics are the pri-mary systems affected.

Lewy Body Dementia (LBD)

Lambon Ralph et al. (2001) report impairmentsin semantic memory in AD and LBD. However,differences were seen between the two groups: ADpatients showed equivalent deficits across pictureand word stimuli, while patients with LBD showedmore severe deficits with picture stimuli. In addi-tion, AD patients showed greater deficits in cate-gory than letter fluency, while LBD patientsexhibited equivalent deficits across the two tasks.In the WAIS vocabulary subtest, similar performancehas been reported in the two groups (Shimomuraet al., 1998). Differentiation between these twosyndromes is mainly based on the visuoperceptualdifficulties seen in LBD relative to AD, in combi-nation with the more impaired memory perform-ance in AD, rather than on the basis of languagetests.

Heterogeneity in MCI and AD

Another issue that must be taken into account isthe considerable variability that exists within ADand MCI populations. MCI is heterogeneous interms of both clinical presentation and etiology.With respect to AD, while language impairmentsare often seen early in the disease course, this is notinevitably the case: Visuospatial and frontal vari-ants of AD have also been described (Caine &Hodges, 2001; Cummings, 2000). No language orsemantic test will have 100% sensitivity and specifi-city for AD; it is only in combination with a varietyof genetic, cognitive, and neuroimaging markersthat these methods can be useful.

Diagnostic criteria for MCI

The Petersen criteria for MCI (Petersen et al.,1999) require that the patient manifest subjectivememory complaints, preferably corroborated byan informant; impaired memory function (usually≥1.5 SD below norms, adjusted for age and educa-tion); generally preserved other cognitive function;and intact activities of daily living. Specific psycho-metric tests are not provided; the diagnosis of MCIthus requires clinical judgment. Furthermore, ithas been reported that a diagnosis of MCI is tem-porally unstable (Ritchie et al., 2001), and the pat-tern of cognitive dysfunction may be intrinsicallyfluctuating in early stages (Feldman & Jacova,2005). One avenue to greater diagnostic accuracymay be serial administration of psychometric tests(Feldman & Jacova, 2005). In this case, creation ofalternate forms of neuropsychological tests is an



important area for development. Given the varyingcriteria used to diagnose MCI, it is hardly surpris-ing that conflicting results have been reported inthe literature with respect to language performancein this population. Future research should focus onidentifying diagnostic criteria for cognitive and eti-ological subtypes of MCI, allowing greater prog-nostic and diagnostic accuracy.

Future directions

The challenge that remains is to develop a diagnos-tic tool that can detect the subtle declines in seman-tic abilities often seen in the very early stages of ADand that is sensitive enough to be useful on an indi-vidual-by-individual basis. While lexical-semanticprocessing is not affected in every case of AD, it iswell established that this domain is typicallyaffected early in the disease course, and it thus con-stitutes a primary target for detection and progno-sis of MCI. On the basis of the research findingsreviewed here, we suggest that the ideal tool for thispurpose will focus on intentional lexical-semanticprocessing, utilizing a temporally precise methodol-ogy. Such a tool may prove useful in the accuratedetection of individuals who are likely to developAD in the future, thus providing the opportunity tocommence pharmacological treatment, psychologi-cal intervention, and family and financial planningas early in the disease course as possible.

One methodology that provides such temporalprecision is the event-related potential (ERP)methodology. For example, as discussed above,Olichney et al. (2002) and Taylor and Olichney(2007) report results indicating that ERP perform-ance may be useful in discriminating those MCIindividuals who will go on to develop AD. Like-wise, ongoing work in our lab indicates alterationsin ERP response to language stimuli in MCIrelative to healthy elderly adults. Our results sug-gest reductions in lexical activation in MCI (Taler& Phillips, 2006), as well as impairments in activa-tion of multiple semantic representations (Taler,Klepousniotou, & Phillips, 2007).

Another area that requires further investigation isthe domain of discourse-level processing in MCI.There is a good deal of research indicating deficits insentence-level language function in mild or minimalAD, both in production (Forbes et al., 2002; Forbes-McKay & Venneri, 2005; Kemper et al., 1993) and incomprehension (Chapman et al., 2002; Welland,Lubinski, & Higginbotham, 2002). Deficits in com-prehension of prosody are also seen in AD and arecorrelated with severity of dementia (Taler, Baum,Saumier, & Chertkow, in press; Testa, Beatty,

Gleason, Orbelo, & Ross, 2001). Such functionshave yet to be thoroughly assessed in MCI, but defi-cits in sentence- or discourse-level processing seemlikely, and preliminary research points to this con-clusion (Chapman et al., 2002). As well as potentialapplications in terms of detection of prodromal AD,better characterization of these deficits in MCI willallow a more complete picture of the neuropsycho-logical profile of these individuals. Discourse andprosody processing are fundamental aspects ofhuman communication. As such, understandinghow these functions are affected in MCI and ADpaves the road for interventions with these individu-als to improve communication with family and car-egivers, which in turn holds promise for an improvedquality of life both for patients and for their families.

Original manuscript received 5 April 2007Revised manuscript accepted 27 June 2007

First published online 26 November 2007

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529

AP

PE

ND

IX A

P

ublis

hed

stud

ies

repo

rtin

g ca

tego

ry fl

uenc

y pe

rfor

man

ce in

MC

I and

pre

clin

ical

AD

Aut

hors

Tes

t us

edG

roup

s+sa

mpl

e si

zes

Dia

gnos

tic

crit

eria

Rec

ruit

men

t pr

oced

ure

Sig

nifi

cant

eff

ects

Eff

ect

size

s (C

ohen

’s d

)

Adl

am e

t al

. (2

006)

LF

(F

,A,S

) &

CF

(a

nim

als,

bir

ds,

frui

t, it

ems,

to

ols,

veh

icle

s)

NE

(n

=30

) M

CI

(n=

10)

mild

AD

(n

=11

)

MC

I: P

eter

sen

crit

eria

A

D: N

INC

DS-

AD

RD

A

crit

eria

(M

cKha

nn e

t al

., 19

84

Mem

ory

Clin

ic a

t A

dden

broo

ke’s

Hos

pita

l, C

ambr

idge

LF

: NE

=M

CI

> A

DC

F: N

E >

MC

I >

AD

LF

: MC

I vs

. AD

: 1.1

4C

F, l

ivin

g: N

E v

s. M

CI:

1.7

3;

MC

I vs

. AD

: 2.0

; C

F, m

anm

ade:

N

E v

s. M

CI:

1.9

4;

MC

I vs

. AD

: 1.5

8A

lber

t et

al.

(200

1)L

F &

CF

Bas

elin

e:

NE

: CD

R=

0P

rint

med

iaC

F: N

E >

con

vert

ers

LF

: NE

> c

onve

rter

s;

qAD

> c

onve

rter

s

CF

, NE

vs.

con

vert

ers:

0.5

8L

F: N

E v

s. c

onve

rter

s: 0

.82;

qA

D v

s. c

onve

rter

s: 0

.61

NE

(n

=42

)qA

D: C

DR

=0.

5qA

D (

n=

123)

A

D: C

DR

=1

3 ye

ar f

ollo

w-u

p:N

E (

n=

32)

stab

le q

AD

(n

=91

)qA

D w

ho c

onve

rted

to

AD

(n

=23

)A

lber

t et

al.

(200

7)L

F &

CF

NE

(n

=33

) N

E: C

DR

-SB

=0

Pri

nt m

edia

No

sign

ific

ant

effe

cts

impa

ired

at

base

line,

sta

ble

over

3 y

ears

(n

=22

)im

pair

ed: C

DR

-SB

bet

wee

n 0.

5 an

d 3

NE

/impa

ired

at

base

line

and

decl

ined

ove

r 3

year

s (n=

95)

NE

/impa

ired

at

base

line

and

conv

erte

d to

dem

enti

a (n

=47

)A

mie

va e

t al

. (2

005)

CF

(co

lors

, an

imal

s, f

ruit

s,

citi

es)

Non

dem

ente

d el

derl

y (n

=1,

050)

, 215

wen

t on

to

deve

lop

dem

enti

a

dem

enti

a: D

SM-I

II-R

Ran

dom

ly s

elec

ted

from

el

ecto

ral l

ists

Low

er b

asel

ine

up t

o 9

year

s pr

evio

usly

and

acc

eler

ated

de

clin

e in

pre

-AD

sub

ject

sA

D: N

INC

DS-

AD

RD

A

crit

eria

Art

ero

et a

l. (2

003)

LF

& C

F

(veg

etab

les)

128

indi

vidu

als

wit

h co

gnit

ive

diff

icul

ties

Cog

niti

ve d

iffi

cult

ies

asce

rtai

ned

usin

g th

e D

eter

iora

tion

Iden

tifi

ed v

ia a

reg

iona

l ge

nera

l pra

ctit

ione

r ne

twor

k

Bes

t pr

edic

tive

mod

el f

or A

D

incl

udes

del

ayed

aud

itor

y ve

rbal

reca

ll+

cons

truc

tion

+

CF

(se

nsit

ivit

y=

99%

, sp

ecif

icit

y=

73%

)C

ogni

tive

Obs

ervé

e (D

EC

O)

scre

enin

g in

stru

men

t (R

itch

ie

& F

uhre

r, 1

992)

Aur

iaco

mbe

et

al.

(200

6)C

F (c

olor

s, a

nim

als,

fr

uits

& c

itie

s)N

onde

men

ted

elde

rly

(n=

156)

, 52

of w

hom

wen

t on

to

deve

lop

AD

Dem

enti

a: D

SM-I

II-R

Ran

dom

ly s

elec

ted

from

el

ecto

ral l

ists

CF

dis

ting

uish

es A

D u

p to

five

ye

ars

prio

r to

dia

gnos

is;

repe

titi

ons

less

rel

iabl

e as

a

mar

ker

CF

: T5,

0.7

8; T

8, 1

.16;

T10

, 1.

62; r

epet

itio

ns: T

5, 0

.38;

T

8, 0

.63;

T10

, 1.2

8A

D: N

INC

DS-

AD

RD

A

crit

eria

(Con

tinu

ed)


530

AP

PE

ND

IX A

(C

ontin

ued)

Aut

hors

Tes

t us

edG

roup

s+sa

mpl

e si

zes

Dia

gnos

tic

crit

eria

use

dR

ecru

itm

ent

proc

edur

eS

igni

fica

nt e

ffec

tsE

ffec

t si

zes

(Coh

en’s

d)

Bäc

kman

et

al.

(200

2)C

F (

item

s at

gr

ocer

y st

ore)

&

LF

(N

,S)

Non

dem

ente

d el

derl

y (n

=33

7), 6

1 of

who

m w

ent

on to

dev

elop

dem

enti

a an

d 69

of

who

m w

ent

on t

o di

e

Dem

enti

a: D

SM-I

II-R

All

inha

bita

nts

of

Kun

gsho

lmen

, Sw

eden

, ag

ed ≥

75 o

n O

ctob

er 1

st,

1987

invi

ted

to

part

icip

ate

Non

conv

erte

rs >

con

vert

ers

on a

ll m

easu

res

CF

: 0.8

8L

F: 0

.82

Bei

nhof

f et

al.

(200

5)C

F (

anim

als)

NE

(n

=57

)M

CI

(n=

48)

AD

(n

=66

)M

D (

n=

61)

MC

I: P

eter

sen

crit

eria

AD

: NIN

CD

S-A

DR

DA

cr

iter

iaM

D: D

SM-I

V c

rite

ria.

Mem

ory

clin

icA

D <

MC

I=M

D <

NE

NE

vs.

MC

I: 1

.04

MC

I vs

. AD

: 1.0

2

Ben

nett

et

al.

(200

2)C

F (

part

of

sum

mar

y m

easu

re

of s

eman

tic

mem

ory)

NE

(n

=58

7);

MC

I (n

=21

1)C

ogni

tive

impa

irm

ent,

but

doe

s no

t mee

t acc

epte

d cr

iter

ia fo

r de

men

tia

Cat

holic

cle

rgy

who

agr

eed

to p

arti

cipa

teSe

man

tic

mem

ory

low

er a

t ba

selin

e, d

eclin

ed m

ore

than

tw

ice

as f

ast

in M

CIs

CF

: 0.8

1

Bla

ckw

ell e

t al

. (2

004)

CF

(an

imal

s, f

ruit

, ho

useh

old

item

s)Su

bjec

tive

/obj

ecti

ve m

emor

y lo

ss (

n=

43),

11

of w

hom

de

velo

ped

AD

wit

hin

32

mon

ths

Nor

mal

per

form

ance

on

test

s of

lang

uage

and

vis

uosp

atia

l fu

ncti

on, p

rese

rved

AD

L,

CD

R=

0.5

Mem

ory

clin

icN

onco

nver

ters

> c

onve

rter

s1.

37

Boz

oki e

t al

. (2

001)

LF

(C

,F,L

)IM

I (n

=48

)P

eter

sen

crit

eria

+

neur

opsy

chol

ogic

al e

vide

nce

(dia

gnos

tic

crit

eria

and

cog

-ni

tive

mea

sure

s fo

r cl

inic

al

chan

ge b

ased

on

thos

e pr

o-po

sed

for

AA

MI)

Mic

higa

n A

lzhe

imer

’s

Dis

ease

Res

earc

h C

ente

rIm

pair

men

t in

≥2

cogn

itiv

e te

sts+

mem

ory

=hi

gher

ris

k of

con

vers

ion

to A

D (

at

4-ye

ar f

ollo

w-u

p: m

emor

y im

pair

men

t on

ly: 2

4%

conv

ersi

on; m

emor

y im

pair

men

t+1

or m

ore

cogn

itiv

e do

mai

ns: 7

7%

conv

ersi

on; m

emor

y im

pair

men

t+2

or m

ore

cogn

itiv

e do

mai

ns: 1

00%

co

nver

sion

).B

scho

r et

al.

(200

1)L

F (

S) &

CF

(a

nim

als)

NE

(n

=40

)IC

D-1

0 cr

iter

ia (

Zau

dig,

199

2)M

emor

y cl

inic

, Dep

t. o

f G

eron

tolo

gy, F

reie

U

nive

rsit

ät B

erlin

NE

> M

CI

> m

ild A

D=

mod

/sev

AD

for

bot

h m

easu

res

CF

: NE

vs.

MC

I, 0

.59,

MC

I vs

. mild

AD

, 0.9

7L

F: N

E v

s. M

CI,

0.8

4, M

CI

vs. m

ild A

D, 0

.50

MC

I (n

=34

)m

ild A

D (

n=

21)

mod

erat

e to

sev

ere

AD

(n=

20)

Cac

capo

lo-V

an

Vlie

t et

al.

(200

3)

LF

(C

,F,L

) &

CF

(a

nim

als,

foo

d &

cl

othi

ng)

NE

(n

=23

0)Q

D: c

ogni

tive

impa

irm

ent

suff

icie

nt o

r cl

ose

to

suff

icie

nt f

or a

dia

gnos

is o

f de

men

tia;

no

func

tion

al

impa

irm

ent

AD

: NIN

CD

S-A

DR

DA

cr

iter

ia

Mem

ory

Dis

orde

rs C

ente

r/re

crui

ted

for

a st

udy

of

cont

rols

LF

: NE

=Q

D; Q

D=

mild

AD

; N

E >

mild

AD

> m

oder

ate

AD

> s

ever

e A

D >

ver

y se

vere

AD

CF

: NE

> Q

D >

mild

AD

>

mod

erat

e A

D >

sev

ere

AD

>

ver

y se

vere

AD

CF

: NE

vs.

QD

: 0.4

3; Q

D v

s.

mild

AD

: 0.4

9; m

ild A

D v

s.

mod

erat

e A

D: 0

.79;

m

oder

ate

AD

vs.

sev

ere

AD

: 0.7

1; s

ever

e A

D v

s.

very

sev

ere

AD

: 1.0

4

QD

(n

=15

5)m

ild A

D (

n=

244)

mod

erat

e A

D (

n=

480)

seve

re A

D (

n=

376)

very

sev

ere

AD

(n=

247)


531

Che

n et

al.

(200

0)L

F &

CF

NE

(n

=48

3), w

ho r

emai

ned

non-

dem

ente

d ov

er 1

0-ye

ar

follo

w-u

p

NIN

CD

S-A

DR

DA

cri

teri

aR

ando

mly

sel

ecte

d fr

om

vote

r re

gist

rati

on li

sts

NE

> in

cide

nt A

D fo

r bo

th L

F

and

CF

; how

ever

, nei

ther

w

as a

bet

ter

pred

icto

r of

in

cide

nt d

emen

tia

than

the

M

MSE

LF

: 0.5

0C

F: 0

.83

Con

vert

ers

to A

D 1

.5 y

ears

af

ter

test

ing

(n=

120)

Che

n et

al.

(200

1)L

F &

CF

NE

(n

=55

1), 6

8 of

who

m

wen

t on

to

deve

lop

AD

NIN

CD

S-A

DR

DA

cri

teri

aR

ando

mly

sel

ecte

d fr

om

vote

r re

gist

rati

on li

sts

Dec

line

in C

F: n

onco

nver

ters

<

con

vert

ers

decl

ine

in L

F:

nonc

onve

rter

s =

con

vert

ers

CF

: 0.2

9

Col

lie e

t al

. (2

002)

CF

Eld

erly

adu

lts

(n=

174)

, 23

of w

hom

wer

e im

pair

ed o

n 3

cons

ecut

ive

asse

ssm

ents

CE

RA

D b

atte

ry (

Mor

ris

et a

l.,

1988

)R

ecru

ited

fro

m a

n on

goin

g st

udy

on a

ging

at

an

inde

pend

ent

rese

arch

in

stit

ute

in M

elbo

urne

, A

ustr

alia

NE

=M

CI

Coo

per

et a

l. (2

004)

CF

(an

imal

s)N

E (

n=

23)

MC

I-A

: Pet

erse

n cr

iter

iaC

linic

for

Alz

heim

er’s

D

isea

se a

nd R

elat

ed

Dis

orde

rs, U

nive

rsit

y of

T

exas

Sou

thw

este

rn

Med

ical

Cen

ter,

Dal

las

Onl

y N

E s

how

ed s

igni

fica

nt

impr

ovem

ent

acro

ss

repe

ated

adm

inis

trat

ions

(2

4 to

96

hour

s ap

art)

MC

I-A

(n

=23

)A

D (

n=

23)

Cro

ot e

t al

. (1

999)

CF

(liv

ing,

4

cate

gori

es &

m

anm

ade,

4

cate

gori

es)

NE

(n

=46

)N

INC

DS-

AD

RD

A c

rite

ria

min

imal

: MM

SE=

24–3

0m

ild: M

MSE

=18

–23

mod

erat

e: M

MSE

=2–

17

Mem

ory

Clin

ic a

t A

dden

broo

ke’s

Hos

pita

l, C

ambr

idge

p-va

lue

not

repo

rted

min

imal

AD

(n

=16

)m

ild A

D (

n=

16)

mod

erat

e A

D (

n=

14)

Cun

je e

t al

. (2

007)

CF

(an

imal

s, c

itie

s &

tow

ns, n

ames

, or

fru

its

&

vege

tabl

es)

NE

(n

=46

)M

CI

(n=

45)

dem

enti

a ( n

=55

)

Subj

ecti

ve m

emor

y lo

ss w

ith

corr

obor

atio

n by

a f

amily

m

embe

r or

frie

nd, n

o de

fici

ts

in A

DL

, no

dem

enti

a

Fiv

e ou

tpat

ient

clin

ics

in

sout

hern

Ont

ario

, and

a

loca

l nur

sing

hom

e

No

diff

eren

ce in

sen

siti

vity

to

MC

I an

d de

men

tia

betw

een

the

four

ver

sion

s; a

ll di

scri

min

ated

bet

wee

n A

D,

MC

I &

NE

par

tici

pant

s;

60-s

econ

d sc

ore

mor

e se

nsit

ive

than

30-

seco

nd

scor

e.

Ani

mal

s, 0

–30

s: 2

.3, 3

1–60

s:

1.5,

0–6

0 s:

3.2

Cit

ies

& t

owns

, 0–3

0 s:

1.9

, 31

–60

s: 1

.5, 0

–60

s: 2

.7

Fru

its

& v

eget

able

s, 0

–30

s:

1.5,

31–

60 s

: 1.3

, 0–6

0 s:

2.5

Nam

es, 0

–30

s: 2

.3, 3

1–60

s:

1.5,

0–6

0 s:

3.2

Dar

tigu

es e

t al

. (1

997)

CF

(co

lors

, an

imal

s, f

ruit

s,

citi

es)

Non

dem

ente

d el

derl

y (n

=2,

726)

, 59

of w

hom

de

velo

ped

AD

in 3

-yea

r fo

llow

-up

DSM

-III

-R c

rite

ria

Ran

dom

ly c

hose

n fr

om

elec

tora

l rol

ls in

Gir

onde

an

d D

ordo

gne,

Fra

nce

CF

was

an

inde

pend

ent

and

very

goo

d pr

edic

tor

of

dem

enti

a/A

D

de J

ager

et

al.

(200

3)C

F (

frui

ts &

ve

geta

bles

)N

E (

n=

51)

MC

I: P

eter

sen

crit

eria

AD

: NIN

CD

S-A

DR

DA

cr

iter

iaV

CI:

Hac

hins

ki c

rite

ria

VaD

: NIN

CD

DS/

AIR

EN

cr

iter

ia (

G. G

old

et a

l. 19

97)

Rec

ruit

ed f

rom

the

Oxf

ord

Pro

ject

To

Inve

stig

ate

Mem

ory

and

Age

ing

(OP

TIM

A)

stud

y

NE

> M

CI

> A

DC

VD

(V

aD+

VC

I) a

lso

exhi

bite

d de

fici

ts

NE

vs.

MC

I: 0

.74

MC

I vs

. AD

: 1.4

8N

E v

s. C

VD

: 1.3

2M

CI

(n=

29)

AD

(n

=60

)V

CI

(n=

8)V

aD (

n=

4)

(Con

tinu

ed)


532

AP

PE

ND

IX A

(C

ontin

ued)

Aut

hors

Tes

t us

edG

roup

s+sa

mpl

e si

zes

Dia

gnos

tic

crit

eria

use

dR

ecru

itm

ent

proc

edur

eS

igni

fica

nt e

ffec

tsE

ffec

t si

zes

(Coh

en’s

d)

Dev

anan

d et

al.

(199

7)L

F &

CF

QD

(n

=62

), 2

6 of

who

m w

ent

on t

o de

velo

p de

men

tia

QD

: cog

niti

ve im

pair

men

t, f

all

betw

een

“nor

mal

” an

d “d

emen

tia”

cat

egor

ies

Mem

ory

Dis

orde

rs C

linic

Bas

elin

e pe

rfor

man

ce o

n C

F:

nonc

onve

rter

s >

con

vert

ers;

se

nsit

ivit

y=

59.3

%,

spec

ific

ity

=55

.6%

; P

PV

=57

.1%

, NP

V=

57.7

%

0.64

Dem

enti

a: D

SM-I

II

crit

eria

AD

: NIN

CD

S-A

DR

DA

cri

teri

a

Dev

anan

d et

al.

(200

6)C

FM

CI

(n=

23),

6 o

f w

hom

wen

t on

to

deve

lop

dem

enti

aA

ge ≥

40;

impa

irm

ent 6

mon

ths

to 1

0 ye

ars;

no

dem

enti

a;

MM

SE ≥

22;

obj

ecti

ve

mem

ory

impa

irm

ent

OR

su

bjec

tive

mem

ory

decl

ine

corr

obor

ated

by

info

rman

t;

+ve

sco

re o

n at

leas

t on

e of

th

e fi

rst

eigh

t it

ems

of t

he

mod

ifie

d B

less

ed F

unct

iona

l A

ctiv

ity

Scal

e (B

less

ed e

t al

., 19

68).

Mem

ory

Dis

orde

rs C

linic

CF

did

not

pre

dict

AD

Dud

as e

t al

. (2

005)

LF

(F

AS)

& C

F

(liv

ing

&

man

mad

e)

NE

(n

=29

)P

eter

sen

crit

eria

Mem

ory

Clin

ic a

t A

dden

broo

ke’s

Hos

pita

l, C

ambr

idge

CF

: NE

> M

CI

> A

DL

F: n

o si

gnif

ican

t ef

fect

sC

F li

ving

: NE

vs.

MC

I, 1

.75;

M

CI

vs. A

D, 1

.16

CF

man

mad

e: N

E v

s. M

CI,

1.

05; M

CI

vs. A

D, 1

.42

MC

I (n

=24

)A

D (

n=

22)

Dw

olat

zky

et a

l. (2

003)

LF

(F

,A,S

) &

CF

(a

nim

als)

NE

(n

=15

)P

eter

sen

crit

eria

Mem

ory

clin

ics

NE

> M

CI

on a

ll te

sts;

bes

t di

scri

min

ant

was

LF

(F

,S)

MC

I (n

=20

)A

D (

n=

19)

Fab

rigo

ule

et a

l. (1

998)

CF

(co

lors

, an

imal

s, f

ruit

s,

citi

es)

nond

emen

ted

elde

rly

(n=

1,15

9), 2

5 of

who

m

deve

lope

d de

men

tia

at

2 ye

ars

(AD

, n=

16)

NIN

CD

S-A

DR

DA

cri

teri

aIn

divi

dual

s ra

ndom

ly

sele

cted

fro

m e

lect

oral

lis

ts

Non

-con

vert

ers

> C

onve

rter

s1.

58


533

Fill

enba

um

et a

l. (2

005)

CF

(an

imal

s)N

E: n

=20

1 (S

eatt

le),

n=

120

(Haw

aii)

CD

R=

0.5:

n=

33 (

Seat

tle)

, n

=65

(H

awai

i)C

DR

=1:

n=

37 (

Seat

tle)

, n

=97

(H

awai

i)C

DR

=2:

n=

33 (

Seat

tle)

, n

=55

(H

awai

i)C

DR

=3,

4,5:

n=

46 (

Seat

tle)

, n

=81

(H

awai

i)

CD

R s

core

Seat

tle:

Kin

g C

ount

y te

leph

one

dire

ctor

ies,

H

ealt

h C

are

Fin

anci

ng

Adm

inis

trat

ion

(now

C

MS)

Med

icar

e re

cipi

ent

lists

, Jap

anes

e-A

mer

ican

or

gani

zati

onal

list

s, a

nd

wor

d of

mou

thH

awai

i: Ja

pane

se-A

mer

ican

m

en b

orn

1900

–191

9,

livin

g in

Oah

u in

196

5,

who

had

bee

n on

the

W

orld

War

II

Sele

ctiv

e Se

rvic

e R

egis

trat

ion

file

CD

R 0

< C

DR

0.5

in b

oth

popu

lati

ons

Fle

ishe

r et

al.

(200

7)C

F21

2 M

CI-

A in

divi

dual

s w

ho

prog

ress

ed t

o A

D w

ithi

n 36

mon

ths

Pet

erse

n cr

iter

iaP

arti

cipa

nts

in a

36-

mon

th

rand

omiz

ed d

rug

tria

lC

F w

as n

ot a

mea

sure

in t

he

mod

el t

hat

was

mos

t pr

edic

tive

of

prog

ress

ion

to A

DF

orbe

s-M

cKay

et

al.

(200

5)C

F (

anim

als

and

frui

t)N

E (

n=

40)

min

imal

AD

(n

=34

)m

ild A

D (

n=

39)

mod

erat

e A

D (

n=

23)

AD

: NIN

CD

S-A

DR

DA

cr

iter

iam

inim

al: M

MSE

24–

29m

ild: M

MSE

19–

23m

oder

ate:

MM

SE 1

3–18

Out

pati

ent

diag

nost

ic a

nd

man

agem

ent

clin

ic in

A

berd

een

AD

> N

E o

n nu

mbe

r of

wor

dsIt

ems

wer

e of

hig

her

freq

uenc

y, s

hort

er, m

ore

typi

cal a

nd h

ad e

arlie

r A

oA

than

con

trol

s’ it

ems

Num

ber

of w

ords

, NE

vs.

m

inim

al A

D: 1

.78;

min

imal

vs

. mild

: 0.9

6; m

ild v

s.

mod

erat

e: 0

.29

AoA

, NE

vs.

min

imal

: 1.8

0G

alvi

n et

al.

(200

5)w

ord

flue

ncy

(typ

e un

spec

ifie

d)N

E (

n=

80)

who

eve

ntua

lly

cam

e to

aut

opsy

CD

R s

core

Indi

vidu

als

enro

lled

in

long

itud

inal

stu

dies

of

heal

thy

agin

g an

d de

men

tia

Bas

elin

e: d

emen

tia

=no

de

men

tia

1.02

Fin

al e

xam

inat

ion:

no

dem

enti

a >

dem

enti

aG

alto

n et

al.

(200

5)C

F (

anim

als,

fru

it,

hous

ehol

d it

ems)

QD

(n

=31

), 1

1 of

who

m h

ad

conv

erte

d to

AD

at

24.2

m

onth

s

QD

: sub

ject

ive

mem

ory

impa

irm

ent,

cor

robo

rate

d by

an

info

rman

t; n

orm

al A

DL

; M

MSE

≥ 2

3; C

DR

=0.

5.A

D: N

INC

DS-

AD

RD

A

crit

eria

Mem

ory

Clin

ic a

t A

dden

broo

ke’s

Hos

pita

l, C

ambr

idge

nonc

onve

rter

s >

con

vert

ers

>

AD

nonc

onve

rter

s vs

. con

vert

ers:

1.

11

AD

(n

=19

)

Ges

lani

et

al.

(200

5)L

F (

P,R

,W)

& C

F

(ani

mal

s)M

CI

(n=

57)

Pet

erse

n cr

iter

ia +

co

rrob

orat

ion

of m

emor

y de

fici

t by

phy

sici

an

Ref

erre

d by

pri

mar

y-ca

re

phys

icia

nsN

o co

mpa

riso

n gr

oup

Gol

dman

et

al.

(200

1)L

F (

S,P

)N

E (

n=

9) p

recl

inic

al A

D

(n=

5)C

linic

ally

non

dem

ente

d, b

ut

neur

itic

and

dif

fuse

pla

ques

th

roug

hout

the

neo

cort

ex

(aut

opsy

fin

ding

s)

Was

hing

ton

Uni

vers

ity’

s A

lzhe

imer

’s d

isea

se

Res

earc

h C

entr

e

No

grou

p di

ffer

ence

s

AD

(n

=10

)

(Con

tinu

ed)


534

AP

PE

ND

IX A

(C

ontin

ued)

Aut

hors

Tes

t us

edG

roup

s+sa

mpl

e si

zes

Dia

gnos

tic

crit

eria

use

dR

ecru

itm

ent

proc

edur

eS

igni

fica

nt e

ffec

tsE

ffec

t si

zes

(Coh

en’s

d)

Góm

ez &

W

hite

(20

06)

LF

(S,

P)

& C

F

(ani

mal

s)N

E (

n=

76)

very

mild

AD

(n

=77

)N

o de

men

tia:

CD

R=

0A

D: N

INC

DS-

AD

RD

A

crit

eria

& D

SM-I

IIve

ry m

ild d

emen

tia:

CD

R=

0.5

Med

ia a

ppea

ls a

nd p

rese

n-ta

tion

s by

res

earc

hers

CF

: NE

> A

D in

wor

ds

gene

rate

d, n

umbe

r of

cl

uste

rs, c

lust

er s

ize

and

num

ber

of s

wit

ches

CF

: wor

ds g

ener

ated

, 1.1

7;

num

ber

of c

lust

ers,

1.0

2;

clus

ter

size

, 0.6

6; n

umbe

r of

sw

itch

es, 0

.93

LF

(P

): N

E >

AD

in w

ords

ge

nera

ted,

num

ber

of

clus

ters

, clu

ster

siz

e an

d nu

mbe

r of

sw

itch

esL

F (

S): N

E >

AD

in w

ords

ge

nera

ted

and

num

ber

of

swit

ches

LF

(P

): w

ords

gen

erat

ed,

0.71

; num

ber

of

clus

ters

, 0.5

2; c

lust

er

size

, 0.5

2; n

umbe

r of

sw

itch

es, 0

.60

LF

(S)

: wor

ds g

ener

ated

, 0.

61; n

umbe

r of

sw

itch

es,

0.55

Gri

ffit

h et

al.

(200

6)L

F (

C,F

,L)

& C

F

(ani

mal

s, f

ruit

s/

vege

tabl

es,

clot

hing

)

NE

(n

=49

)P

eter

sen

crit

eria

Mem

ory

diso

rder

s cl

inic

or

rec

ruit

ed f

rom

co

mm

unit

y

LF

: no

effe

cts

CF

: NE

vs.

MC

I, 0

.73;

no

ncon

vert

ers

vs.

conv

erte

rs, 0

.70

MC

I (n

=49

)C

F: N

E >

MC

I; n

onco

nver

ters

>

con

vert

ers

Gru

ndm

an

et a

l. (2

004)

CF

NE

(n

=10

7)P

eter

sen

crit

eria

, CD

R=

0.5

Adv

erti

sing

cam

paig

n ta

rget

ing

elde

rly

subj

ects

in

cit

ies

wit

h A

lzhe

imer

D

isea

se C

oope

rati

ve

Stud

y (A

DC

S) s

ites

NE

> M

CI

0.87

MC

I (n

=76

9)

Gua

rch

et a

l. (2

004)

LF

(P

)N

E (

n=

34)

SML

(n

=43

), 1

0 of

who

m

wen

t on

to

deve

lop

AD

Subj

ecti

ve m

emor

y lo

ss;

neur

opsy

chol

ogic

al t

ests

not

us

ed a

s in

clus

ion/

excl

usio

n cr

iter

ia.

Clin

ical

psy

chol

ogy

serv

ice

at t

he H

ospi

tal C

linic

i P

rovi

ncia

l, B

arce

lona

.

NE

> S

ML

NE

vs.

SM

L: 0

.61

Non

conv

erte

rs v

s. c

onve

rter

s,

rete

st: 0

.95

SML

: bas

al=

rete

stba

sal:

nonc

onve

rter

s=co

nver

ters

rete

st: n

onco

nver

ters

>

conv

erte

rsH

anni

nen

et a

l. (1

995)

LF

(P

,A,S

) &

CF

(a

nim

als)

AA

MI

(n=

229)

At

follo

w-u

p (3

.6 y

ears

late

r on

ave

rage

), 1

04 A

AM

Is,

16 d

emen

tia

case

s,

13 m

ild d

eclin

e ca

ses

and

17 n

orm

al m

emor

y

AA

MI

crit

eria

(C

rook

et

al.,

1986

)M

emor

y R

esea

rch

Uni

t of

the

Dep

artm

ent

of

Neu

rolo

gy a

t th

e U

nive

rsit

y of

Kuo

pio

in

Eas

tern

Fin

land

Bes

t pr

edic

tion

of

dem

enti

a us

ed s

ix m

easu

res,

incl

udin

g bo

th C

F a

nd L

F.

LF

: dem

enti

a vs

. NE

, 1.0

9;

CF

: dem

enti

a vs

. NE

, 1.9

1;

dem

enti

a vs

. AA

MI,

1.4

9;

dem

enti

a vs

. mild

dec

line,

1.

64A

t fo

llow

-up,

NE

> d

emen

tia

on L

F, a

ll gr

oups

>

dem

enti

a on

CF

.H

odge

s,

Erz

incl

iogl

u,

& P

atte

rson

(2

006)

As

Hod

ges

&

Pat

ters

on (

1995

)N

E (

n=

24)

Gru

ndm

an e

t al

. (20

04)

crit

eria

Mem

ory

Clin

ic a

t A

dden

broo

ke’s

Hos

pita

l, C

ambr

idge

7/10

MC

Is s

how

ed d

efic

its

at

base

line

and

8/10

at

the

end

of t

he f

irst

yea

rM

CI

(n=

10)


535

Hod

ges

&

Pat

ters

on

(199

5)

CF

for

six

mai

n ca

tego

ries

[lan

d an

imal

s, s

ea

crea

ture

s, b

irds

, ho

useh

old

item

s,

vehi

cles

, mus

ical

in

stru

men

ts] a

nd

two

subc

ateg

orie

s [b

reed

s of

dog

, ty

pes

of b

oat]

NE

(n

=24

)N

INC

DS-

AD

RD

A c

rite

ria

Mem

ory

Clin

ic a

t A

dden

broo

ke’s

Hos

pita

l, C

ambr

idge

NE

> m

inim

al >

mild

>

mod

erat

e on

all

subt

ests

Liv

ing:

NE

vs.

min

imal

A

D, 2

.0;

min

imal

AD

vs.

mild

AD

, 0.7

; m

ild A

D v

s. m

oder

ate

AD

, 1.

37M

an-m

ade:

NE

vs.

min

imal

A

D, 2

.34;

m

inim

al A

D v

s. m

ild A

D, 0

.47;

mild

AD

vs.

mod

erat

e A

D,

1.94

min

imal

AD

(n

=17

)m

ild A

D (

n=

52)

mod

erat

e A

D (

n=

18)

Jaco

bs e

t al

. (1

995)

LF

& C

FN

onde

men

ted

elde

rly

(n=

443)

, 41

of w

hom

had

de

velo

ped

AD

at

follo

w-u

p (o

n av

erag

e 2.

05 y

ears

late

r)

NIN

CD

S-A

DR

DA

cri

teri

aN

orth

Man

hatt

an

Agi

ng P

roje

ct, a

co

mm

unit

y-ba

sed,

ep

idem

iolo

gic

stud

y of

de

men

tia

in n

orth

ern

Man

hatt

an, N

Y.

No

sign

ific

ant

effe

cts

repo

rted

Jone

s et

al.

(200

6)L

F (

N,S

) &

CF

(g

roce

ry s

tore

it

ems)

NE

(n

=26

7)D

SM-I

II-R

and

Hac

hins

ki

Isch

emic

Sca

le (

Hac

hins

ki

et a

l., 1

974)

.

All

inha

bita

nts

of

Kun

gsho

lmen

, Sw

eden

, ag

ed ≥

75 o

n O

ctob

er 1

st,

1987

invi

ted

to

part

icip

ate

LF

: pre

clin

ical

AD

=

prec

linic

al V

aDC

F: p

recl

inic

al A

D <

pr

eclin

ical

VaD

LF

: AD

vs.

NE

, 0.5

6pr

eclin

ical

AD

(n

=66

)C

F: A

D v

s. V

aD, 0

.52;

A

D v

s. N

E, 0

.65

prec

linic

al V

aD (

n=

20)

Jorm

et

al.

(200

5)C

F (

4-le

gged

an

imal

s)Ja

pane

se-A

mer

ican

men

age

d 71

–93

(n=

1611

), 5

2 of

w

hom

wen

t on

to

deve

lop

dem

enti

a

DSM

III

-RR

ecru

ited

fro

m p

opul

atio

nP

redi

cted

inci

dent

dem

enti

a up

to

3 y

ears

bef

ore

onse

t bu

t no

t 3–

6 ye

ars

befo

re o

nset

.

0.65

Kal

be e

t al

. (2

004)

CF

(su

perm

arke

t)N

E (

n=

145)

MC

I (n

=97

)A

D (

n=

121)

NE

: CD

R=

0M

CI:

Pet

erse

n cr

iter

iaA

D: N

INC

DS-

AD

RD

A

crit

eria

; CD

R=

1 or

2

Mem

ory

Clin

icN

E >

MC

I >

AD

NE

<60

yea

rs v

s. N

E ≥

60

year

s: 0

.30

NE

≥60

yea

rs v

s. M

CI:

1.2

5M

CI

vs. A

D (

MM

SE≥2

1):

0.99

AD

(M

MSE

≥21)

vs.

AD

(M

MSE

<21

): 0

.61

Kar

rasc

h et

al.

(200

5)C

FN

E (

n=

15)

Pet

erse

n cr

iter

iaC

omm

unit

y so

urce

sN

E>

AD

, not

MC

IM

CI

(n=

15)

AD

(n

=15

)L

am e

t al

. (2

006)

CF

(an

imal

s,

frui

t, v

eget

able

s)

– 30

-sec

ond

and

60-s

econ

d sc

ores

NE

(n

=11

8)Q

D (

n=

150)

mild

AD

(n

=63

)

NE

: CD

R=

0C

omm

unit

y so

cial

cen

tres

an

d re

side

ntia

l hos

tels

for

the

elde

rly

in H

ong

Kon

g

NE

> Q

D >

mild

AD

for

bot

h 30

-sec

ond

and

60-s

econ

d sc

ores

30-s

econ

d: N

E v

s. Q

D, 1

.07;

Q

D v

s. A

D, 1

.10

60-s

econ

d: N

E v

s. Q

D, 1

.11;

Q

D v

s. A

D, 1

.16

QD

: CD

R=

0.5

mild

AD

: CD

R=

1

(Con

tinu

ed)


536

AP

PE

ND

IX A

(C

ontin

ued)

Aut

hors

Tes

t us

edG

roup

s+sa

mpl

e si

zes

Dia

gnos

tic

crit

eria

use

dR

ecru

itm

ent

proc

edur

eS

igni

fica

nt e

ffec

tsE

ffec

t si

zes

(Coh

en’s

d)

Lam

bon

Ral

ph

et a

l. (2

003)

As

Hod

ges

&

Pat

ters

on (

1995

)N

E (

n=

48)

Subj

ecti

ve m

emor

y im

pair

men

t,

corr

obor

ated

by

a sp

ouse

/fa

mily

mem

ber;

pre

serv

atio

n of

AD

L; i

mpa

irm

ent

on a

t le

ast

one

test

of

mem

ory;

no

rmal

per

form

ance

on

test

s of

lang

uage

, vis

uosp

atia

l and

ex

ecut

ive

func

tion

; M

MSE

> 2

4.

Mem

ory

Clin

ic a

t A

dden

broo

ke’s

Hos

pita

l, C

ambr

idge

NE

=M

CI

> A

D (

defi

ned

as

>2

SD

dif

fere

nce)

MC

I (n

=17

)m

ild A

D (

n=

22)

mod

erat

e A

D (

n=

8)se

vere

AD

(n

=8)

Lau

kka

et a

l. (2

004)

LF

(N

,S)

& C

F

(foo

d it

ems)

NE

(n

=14

9)in

cide

nt A

D (

n=

43)

inci

dent

VaD

(n=

15)

DSM

-III

-RH

achi

nski

Isc

hem

ic S

cale

(H

achi

nski

et

al.,

1974

).

All

inha

bita

nts

of

Kun

gsho

lmen

, Sw

eden

, ag

ed ≥

75 o

n O

ctob

er

1st,

198

7 in

vite

d to

pa

rtic

ipat

e

NE

> A

D=

VaD

CF

: NE

vs.

AD

,0.

85L

F: N

E v

s. A

D, 0

.76

Lee

et

al. (

2006

)C

F (

anim

als)

QD

(n=

72),

14

of w

hom

pr

ogre

ssed

to

AD

in 3

yea

rsC

DR

=0.

5O

ne p

ublic

hea

lth

cent

er

and

2 m

emor

y cl

inic

s in

K

orea

nonc

onve

rter

s=co

nver

ters

Lóp

ez e

t al

. (2

006)

CF

(an

imal

s, b

irds

, do

gs)

NE

(n

=37

4)M

CI-

A (

n=

10)

MC

I-M

D (

n=

28)

MC

I-A

: >1.

5 S

Ds

belo

w

cont

rols

in d

elay

ed

reca

ll+

decl

ine

in c

ogni

tive

fu

ncti

onin

g; M

CI-

MD

: >1.

5 S

Ds

in a

t le

ast

one

cogn

itiv

e do

mai

n ot

her

than

mem

ory/

one

abno

rmal

tes

t in

≥2

dom

ains

.

5,20

1 no

nins

titu

tion

aliz

ed

indi

vidu

als

over

65;

re

crui

ted

from

fou

r co

mm

unit

ies

usin

g P

art

A M

edic

are

list

in

1988

–198

9; 6

87

Afr

ican

-Am

eric

ans

recr

uite

d in

sam

e m

anne

r in

199

2–19

93

Ani

mal

s: M

CI-

A a

nd

MC

I-M

D <

NE

Ani

mal

s, M

CI-

A v

s. N

E:

0.94

; MC

I-M

D v

s. N

E:

0.84

Bir

ds a

nd d

ogs:

M

CI-

MD

< N

EB

irds

, MC

I-M

D v

s. N

E: 0

.88

Dog

s, M

CI-

MD

vs.

NE

: 0.6

0

Mas

ur e

t al

. (1

994)

CF

(fr

uits

, an

imal

s, f

low

ers

and

vege

tabl

es)

nond

emen

ted

elde

rly

(n=

317)

, 64

of

who

m d

evel

oped

de

men

tia

in a

fol

low

-up

of

at le

ast

4 ye

ars

Dem

enti

a: D

SM-I

IIR

ecru

ited

fro

m c

omm

unit

yA

ctua

rial

mod

el in

clud

ing

dela

yed

reca

ll, C

F, t

he

FO

ME

(F

uld,

198

1) a

nd

the

WA

IS D

igit

Sym

bol

subt

est (

Wec

hsle

r, 1

955)

can

id

enti

fy s

ubgr

oups

wit

h ve

ry

low

/ver

y hi

gh c

hanc

e of

de

velo

ping

dem

enti

a.

AD

: NIN

CD

S-A

DR

DA

cr

iter

ia

Meg

uro

et a

l. (2

004)

CF

(4-

legg

ed

anim

als)

NE

(n

=96

8)C

DR

0.5

, AD

(n

=95

)C

DR

0.5

, UD

(n

=94

)C

DR

0.5

, ID

(n

=22

7)C

DR

0.5

, oth

ers

(n=

37)

CD

R 1

and

2 (

n=

80)

UD

: onl

y m

emor

y is

impa

ired

ID: i

mpa

irm

ent i

n m

emor

y an

d ≤2

oth

er c

ogni

tive

dom

ains

othe

rs: i

mpa

irm

ent

in m

emor

y an

d ≥3

oth

er c

ogni

tive

do

mai

nsD

emen

tia:

DSM

-III

-R

All

olde

r re

side

nts

in T

ajir

i w

ere

targ

eted

CD

R 0

< C

DR

0.5

< C

DR

< 1

an

d 2

CD

R 0

vs.

0.5

: 0.3

2C

DR

0.5

vs.

1&

2: 1

.20

CD

R 0

.5 (

AD

vs.

UD

): 0

.77

CD

R 0

.5 (

AD

vs.

ID

): 0

.67

CD

R 0

.5 (A

D v

s. o

ther

s): 0

.78

CD

R 0

.5 (D

AT

) <

oth

er C

DR

0.

5 ca

tego

ries


537

Mio

shi e

t al

. (2

006)

CF

(an

imal

s, f

ruit

, ho

useh

old

item

s)N

E (

n=

63)

MC

I (n

=36

)A

D (

n=

67)

LB

D (

n=

20)

FT

D (

n=

55)

MC

I: G

rund

man

et

al. (

2004

) cr

iter

iaM

emor

y C

linic

, Ear

ly O

nset

D

emen

tia

Clin

ic a

nd

Dru

g M

onit

orin

g C

linic

at

Add

enbr

ooke

’s

Hos

pita

l, C

ambr

idge

NE

> M

CI

> d

emen

tia

NE

vs.

MC

I, 0

.9; M

CI

vs.

dem

enti

a, 1

.23

AD

: NIN

CD

S-A

DR

DA

cr

iter

iaL

BD

: McK

eith

et

al. (

2000

)F

TD

: Nea

ry e

t al

. (19

98)

Mor

ris

et a

l. (2

001)

LF

(S,

P)

NE

(n

=17

7)N

E: C

DR

=0

Rec

ruit

ed t

hrou

gh m

edia

No

grou

p ef

fect

suA

D (

n=

53)

MC

I: C

DR

=0.

5iA

D (n

=69

)iA

D: C

DR

=0.

5A

D (

n=

105)

AD

: CD

R=

0.5;

clin

ical

cri

teri

a de

scri

bed

in M

orri

s, M

cKee

l, F

ullin

g, T

orac

k &

Ber

g,

1988

aM

urph

y et

al.

(200

6)L

F (

F)

& C

F

(ani

mal

s)N

E (

n=

46)

MC

I-A

(n

=33

)A

D (

n=

33)

MC

I-A

: Pet

erse

n (2

004)

cri

teri

aA

D: N

INC

DS-

AD

RD

Acr

iter

ia

Phy

sici

an r

efer

rals

an

d ne

wsp

aper

ad

vert

isem

ents

LF

: NE

> A

DC

F: N

E >

MC

I-A

> A

DC

F: N

E v

s. M

CI-

A, 0

.49;

N

E v

s. A

D, 1

.07;

M

CI-

A v

s. A

D, 0

.68

Nie

lsen

et

al.

(199

9)C

F (

anim

als)

Non

dem

ente

d el

derl

y (n

=2,

452)

, 102

of

who

m

deve

lope

d de

men

tia in

2 y

ears

NIN

CD

S-A

DR

DA

cri

teri

aR

ando

mly

dra

wn

from

th

e po

pula

tion

NE

> in

cide

nt A

D0.

67

Nor

dlun

d et

al.

(200

5)L

F (

F,A

,S)

NE

(n

=35

)Su

bjec

tive

and

obj

ecti

ve

mem

ory

impa

irm

ent

> 6

mon

ths;

pos

itiv

e ou

tcom

e on

ste

pwis

e co

mpa

rati

ve

stat

us a

naly

sis (

STE

P, W

allin

et

al.,

199

6), I

-Fle

x (R

oyal

l et

al.,

199

2), M

MSE

or C

DR

; M

MSE

≥25

; not

mor

e th

an

2 +

ve o

utco

mes

on

STE

P

Mem

ory

clin

icN

E=

MC

IM

CI

(n=

112)

Öst

berg

et

al.

(200

5)L

F (

FA

S), C

F

(ani

mal

s) &

ver

b fl

uenc

y

SCI

( n=

40)

MC

I: P

eter

sen

crit

eria

Dep

t of

Ger

iatr

ics,

H

uddi

nge

Uni

vers

ity

Hos

pita

l, du

e to

cog

niti

ve

com

plai

nts

Ove

rall:

SC

I >

MC

I >

AD

MC

I (n

=60

)A

D: D

SM-I

VC

F: S

CI

> M

CI

> A

DA

D (

n=

57)

LF

: SC

I=M

CI

> A

D

Ver

b fl

uenc

y: S

CI

> M

CI

>

AD

Per

ry e

t al

. (2

000)

CF

(an

imal

s, b

irds

, w

ater

cre

atur

es,

hous

ehol

d it

ems,

ve

hicl

es, m

usic

al

inst

rum

ents

)

NE

(n

=44

)N

INC

DS-

AD

RD

A c

rite

ria

Pat

ient

s un

derg

oing

ev

alua

tion

at

the

Uni

vers

ity

of C

ambr

idge

N

euro

logy

uni

t

NE

> m

inim

al A

D >

mild

AD

NE

vs.

min

imal

AD

: 1.4

2;

min

imal

AD

vs.

mild

AD

: 1.

15m

inim

al A

D (

n=

13)

min

imal

: MM

SE=

24–3

0m

ild A

D (

n=

14)

mild

: MM

SE=

18–2

3

Pet

erse

n et

al.

(199

9)L

FN

E (

n=

234)

MC

I (n

=76

)m

ild A

D (

n=

106)

MC

I: m

emor

y co

mpl

aint

; no

rmal

AD

L; n

orm

al g

ener

al

cogn

itiv

e fu

ncti

on; a

bnor

mal

m

emor

y fo

r ag

e; n

ot

dem

ente

d; C

DR

=0.

5.

Com

mun

ity

(sub

ject

s re

ceiv

ing

gene

ral m

edic

al

care

at

May

o C

linic

) an

d re

gion

al (

eval

uati

on o

f co

gnit

ive

diff

icul

ties

at

May

o A

lzhe

imer

’s

Dis

ease

Cen

ter)

NE

> M

CI=

AD

NE

vs.

MC

I: 5

.86

mild

AD

: CD

R=

0.5–

1.0

(Con

tinu

ed)


538

AP

PE

ND

IX A

(C

ontin

ued)

Aut

hors

Tes

t us

edG

roup

s+sa

mpl

e si

zes

Dia

gnos

tic

crit

eria

use

dR

ecru

itm

ent

proc

edur

eS

igni

fica

nt e

ffec

tsE

ffec

t si

zes

(Coh

en’s

d)

Rib

eiro

et

al.

(200

6)C

F (

food

pro

duct

s)N

E (

n=

63)

Subj

ecti

ve m

emor

y co

mpl

aint

s;

≥1.5

SD

bel

ow n

orm

al o

n de

laye

d re

call;

pre

serv

ed

AD

L; m

aint

aine

d pr

ofes

sion

al, s

ocia

l and

fa

mili

al a

ctiv

itie

s, s

core

<

3 on

the

fir

st p

art

of t

he

Ble

ssed

Dem

enti

a Sc

ale;

pr

eser

ved

gene

ral c

ogni

tive

fu

ncti

on.

Dem

enti

a O

utpa

tien

t C

linic

, Hos

pita

l San

ta

Mar

ia, a

nd a

Mem

ory

Clin

ic, L

isbo

n

NE

> A

AC

D

NE

> A

AM

IM

CI

(n=

116)

Ric

hard

s et

al.

(199

9)C

ombi

ned

scor

e of

L

F (

P)

and

CF

(v

eget

able

s)

111

indi

vidu

als,

cla

ssif

ied

as

NE

(n

=74

), A

AM

I (n

=37

),

or A

AC

D (

n=

39).

AA

MI:

mem

ory

impa

irm

ent,

no

dem

enti

aR

ando

mly

rec

ruit

ed f

rom

60

0 ge

nera

l med

ical

pr

acti

ces

in s

outh

ern

Fra

nce

NE

> A

AC

D

NE

> A

AM

IA

AM

I: 0

.61

AA

CD

: 0.6

4A

AC

D: i

mpa

irm

ent

in o

ne

dom

ain:

mem

ory/

lear

ning

, at

tent

ion/

con

cent

rati

on,

visu

ospa

tial

rea

soni

ng,

lang

uage

, vis

uosp

atia

l fu

ncti

onR

ubin

et

al.

(199

8)L

F (

P,S

)N

E (

n=

82),

10

of w

hom

wen

t on

to

deve

lop

AD

, 6 iA

D,

and

11 u

ncer

tain

dem

enti

a

CD

R >

0R

ecru

ited

fro

m t

he

com

mun

ity

No

sign

ific

ant

diff

eren

ces.

Saxt

on e

t al

. (2

004)

LF

(P

,S)

& C

F

(fru

it)

Non

dem

ente

d el

derl

y (n

=69

3), 7

2 of

who

m

deve

lope

d A

D w

ithi

n 1.

5–8

year

s (1

.5–3

.4 y

ears

: n=

24;

3.5–

5.0

year

s: n

=20

; 5.1

–8.1

ye

ars:

n=

28)

NIN

CD

S-A

DR

DA

cri

teri

aSe

lect

ed f

rom

par

tici

pant

s re

crui

ted

from

the

co

mm

unit

y as

par

t of

the

C

ardi

ovas

cula

r H

ealt

h St

udy.

CF

sig

nifi

cant

pre

dict

or o

f A

D u

p to

5 y

ears

pri

or t

o di

agno

sis.

Schm

idtk

e &

H

erm

enei

t (2

007)

CF

(an

imal

s)M

CI

(n=

88);

75

avai

labl

e fo

r fo

llow

-up

Pet

erse

n cr

iter

iaM

emor

y cl

inic

Non

conv

erte

rs=

conv

erte

rs,

alth

ough

z-s

core

was

low

(–

0.9)

for

ent

ire

MC

I sa

mpl

eSm

all e

t al

. (1

997)

LF

(N

,S)

& C

F

(foo

d)N

E (

n=

179)

Dem

enti

a: D

SM-I

V c

rite

ria;

ty

pe a

sses

sed

by st

anda

rdiz

ed

crit

eria

All

inha

bita

nts

of

Kun

gsho

lmen

, Sw

eden

, ag

ed ≥

75 o

n O

ctob

er

1st,

198

7 in

vite

d to

pa

rtic

ipat

e

Bas

elin

e sc

ores

: NE

> in

cide

nt

AD

for

both

CF

and

LF

LF

: 0.8

1in

cide

nt A

D (

n=

26)

CF

: 0.8

2

Stan

dish

et

al.

(200

7)C

FN

E (

n=

174)

MC

I (n

=16

6)de

men

tia

(n=

302)

Dem

enti

a: D

SM-I

VSp

ecia

lty

geri

atri

c cl

inic

s in

so

uthe

rn O

ntar

ioN

E >

MC

I >

dem

enti

aA

D: N

INC

DS-

AD

RD

A

crit

eria

MC

I: P

eter

sen

crit

eria


539

Swai

nson

et

al.

(200

1)L

F (

F,A

,S)

& C

F

(ani

mal

s, f

ruit

s,

hous

ehol

d it

ems)

NE

(n

=39

)Q

D (

n=

43)

mild

AD

(n

=26

)M

D (

n=

37)

QD

: mem

ory

impa

irm

ent

but

not

mee

ting

cri

teri

a fo

r de

men

tia/

depr

essi

on

AD

: NIN

CD

S-A

DR

DA

cri

teri

a

Mem

ory

clin

ic,

Add

enbr

ooke

’s H

ospi

tal;

Psy

chia

try

Dep

artm

ent,

W

est

Suff

olk

Hos

pita

l; M

enta

l Hea

lth

Serv

ices

, A

dden

broo

ke’s

NH

S T

rust

CF

: QD

+M

D+

NE

> A

D;

MD

+N

E >

QD

; NE

> M

DL

F: Q

D+

MD

+N

E >

AD

No

sign

ific

ant

corr

elat

ion

betw

een

base

line

perf

orm

ance

and

MM

SE

decl

ine

in Q

D in

divi

dual

s

MD

: DSM

-IV

Tab

ert

et a

l. (2

006)

AN

T (G

oodg

lass

&

Kap

lan,

198

3)L

F (

C,F

,L)

NE

(n

=83

)M

CI

(n=

148)

Age

≥40

; cog

niti

ve im

pair

men

t fo

r 6

mon

ths–

10 y

ears

; C

DR

0–0

.5.

Mem

ory

diso

rder

s cl

inic

; N

E r

ecru

ited

by

adve

rtis

emen

t

NE

> M

CI

AN

T: N

E v

s. M

CI,

0.7

2;

Non

conv

erte

rs v

s.

conv

erte

rs, 0

.59

LF

: NE

vs.

MC

I, 0

.43;

N

onco

nver

ters

vs.

co

nver

ters

, 0.7

2

For

mem

ory:

MM

SE, S

RT

, W

AIS

–R p

erfo

rman

ce I

Q.

Non

conv

erte

rs >

con

vert

ers

If n

o fo

rmal

cog

niti

ve d

efic

it:

subj

ecti

ve m

emor

y de

clin

e,

posi

tive

sco

re o

n 1

or m

ore

of

the

firs

t 8

item

s of

the

m

odif

ied

Ble

ssed

Fun

ctio

nal

Act

ivit

y Sc

ale.

Tia

n et

al.

(200

3)L

FQ

D (

n=

195)

, 135

see

n fo

r fo

llow

up a

t 24

.5 m

onth

s;

37 c

onve

rted

to

dem

enti

a

Obj

ecti

ve e

vide

nce

of c

ogni

tive

im

pair

men

t bu

t no

dem

enti

aB

rist

ol M

emor

y D

isor

ders

C

linic

Non

conv

erte

rs >

con

vert

ers

0.40

Tou

chon

&

Rit

chie

(1

999)

LF

(P

) &

CF

(v

eget

able

s)N

E (

n=

150)

359

init

ially

non

dem

ente

d in

divi

dual

s: 2

2 de

velo

ped

AD

in t

hird

yea

r

Dem

enti

a: D

SM-I

II-R

A

D: N

INC

DS-

AD

RD

A

crit

eria

Gen

eral

pra

ctit

ione

r re

crui

tmen

t ne

twor

kC

F: N

E >

MC

I 2

year

s pr

ior

to

diag

nosi

s, in

depe

nden

t of

ed

ucat

ion

effe

cts

LF

: NE

> M

CI,

but

inte

ract

ed

sign

ific

antl

y w

ith

educ

atio

n.

CF

: 2.0

4L

F: 1

.51

Vog

el e

t al

. (2

005)

CF

(an

imal

s)N

E (

n=

58)

pred

emen

tia

AD

(n

=22

)m

ild A

D (

n=

102)

AD

: NIN

CD

S-A

DR

DA

cr

iter

iaC

open

hage

n U

nive

rsit

y H

ospi

tal M

emor

y C

linic

NE

> p

rede

men

tia

AD

> A

D

pred

emen

tia

AD

: Pet

erse

n cr

iter

ia+

subs

eque

nt

prog

ress

ion

to A

D (

10–3

0 m

onth

s la

ter)

Wan

g et

al.

(200

6)C

F (

4-le

gged

an

imal

s)N

E (

n=

20)

MC

I: P

eter

sen

crit

eria

Neu

rolo

gica

l clin

ics

NE

> M

CI

> A

DN

E v

s. M

CI:

1.2

5M

CI

(n=

58)

AD

: NIN

CD

S-A

DR

DA

cr

iter

iaM

CI

vs. A

D: 0

.59

AD

(n

=20

)

Not

e. E

ffec

t si

zes

are

repo

rted

whe

re p

ossi

ble.

AA

MI=

age-

asso

ciat

ed m

emor

y im

pair

men

t. A

D=

Alz

heim

er’s

dis

ease

. AD

L=

acti

viti

es o

f da

ily li

ving

. AN

T=

Ani

mal

Nam

ing

Tes

t. A

oA=

age

of a

cqui

si-

tion

. CD

R=

Clin

ical

Dem

entia

Rat

ing

Scal

e. C

F=

cate

gory

flue

ncy.

CV

D=

cere

brov

ascu

lar

dise

ase.

DSM

-III

-R=

Dia

gnos

tic a

nd S

tatis

tica

l Man

ual o

f Men

tal D

isor

ders

—T

hird

Edi

tion,

Rev

ised

. FO

ME

=F

uld

Obj

ect

Mem

ory

Eva

luat

ion.

iA

D=

inci

pien

t A

D.

ID=

inci

pien

t de

men

tia.

IM

I=is

olat

ed m

emor

y im

pair

men

t. L

BD

=L

ewy

body

dem

enti

a. L

F=

lett

er f

luen

cy.

MC

I=m

ild c

ogni

tive

im

pair

men

t.M

CI-

A=

MC

I-am

nest

ic. M

CI-

MD

=M

CI-

mul

tipl

e do

mai

n. M

D=

maj

or d

epre

ssiv

e di

sord

er. M

MSE

=M

ini M

enta

l Sta

te E

xam

inat

ion.

NE

=no

rmal

eld

erly

. NIN

CD

S-A

DR

DA

=N

atio

nal I

nsti

tute

of

Neu

rolo

gica

l and

Com

mun

icat

ive

Dis

orde

rs a

nd S

trok

e–A

lzhe

imer

’s D

isea

se a

nd R

elat

ed D

isor

ders

Ass

ocia

tion

. qA

D=

ques

tion

able

Alz

heim

er’s

dis

ease

. QD

=qu

esti

onab

le d

emen

tia.

SC

I=su

bjec

tive

cogn

itiv

e im

pair

men

t. S

ML

=su

bjec

tive

mem

ory

loss

. SR

T =

Bus

cke

Sele

ctiv

e R

emin

ding

Tes

ts.

UD

=un

cert

ain

dem

enti

a. V

aD=

vasc

ular

dem

enti

a. V

CI=

vasc

ular

cog

niti

ve i

mpa

irm

ent.

WA

IS-

R=

Wec

hsle

r A

dult

Int

ellig

ence

Sca

le–R

evis

ed.


540

AP

PE

ND

IX B

Pub

lishe

d st

udie

s re

port

ing

nam

ing

perf

orm

ance

in M

CI a

nd p

recl

inic

al A

D

Aut

hors

Tes

t us

edG

roup

s+sa

mpl

e si

zes

Dia

gnos

tic

crit

eria

R

ecru

itm

ent

proc

edur

eS

igni

fica

nt e

ffec

tsE

ffec

t si

zes

(Coh

en’s

d)

Adl

am e

t al

. (20

06)

nam

ing

64 li

ne

draw

ings

NE

(n

=30

)M

CI

(n=

10)

mild

AD

(n

=11

)

MC

I: P

eter

sen

crit

eria

AD

: NIN

CD

S-A

DR

DA

cri

teri

aM

emor

y C

linic

at

Add

enbr

ooke

’s

Hos

pita

l, C

ambr

idge

NE

=M

CI

> A

DM

CI

vs. A

D: 0

.82

Agg

arw

al e

t al

. (2

005)

BN

T (

20 it

ems)

MC

I (n

=21

8), 8

2 of

who

m

wen

t on

to

deve

lop

AD

MC

I: c

ogni

tive

impa

irm

ent

but

do

not

mee

t N

INC

DS-

AD

RD

A

crit

eria

for

dem

enti

aA

D: N

INC

DS-

AD

RD

A c

rite

ria

Cat

holic

cle

rgy

who

agr

eed

to p

arti

cipa

teR

educ

ed se

man

tic m

emor

y (c

ompo

site

sco

re o

f B

NT

, Ext

ende

d R

ange

V

ocab

ular

y, N

AR

T)

pred

icte

d A

D (

rela

tive

ri

sk=

0.62

); h

owev

er,

epis

odic

mem

ory

impa

irm

ent

stro

nger

pr

edic

tor

Alb

ert

et a

l. (2

001)

BN

T (

15 it

ems)

Bas

elin

e:N

E: C

DR

=0

Pri

nt m

edia

No

sign

ific

ant

effe

cts

NE

(n

=42

)qA

D: C

DR

=0.

5qA

D (

n=

123)

AD

: CD

R=

13

year

fol

low

-up:

NE

(n

=32

)st

able

qA

D (

n=

91)

qAD

who

con

vert

ed t

o A

D

(n=

23)

Alb

ert

et a

l. (2

007)

BN

T (

15 it

ems)

NE

(n

=33

)N

E: C

DR

-SB

=0

Pri

nt m

edia

No

sign

ific

ant

effe

cts

Indi

vidu

als

wit

h m

emor

y im

pair

men

t, s

tabl

e ov

er 3

ye

ars

(n=

22)

mem

ory

impa

irm

ent:

CD

R-S

B

betw

een

0.5

and

3

NE

/impa

ired

at

base

line

and

decl

ined

ove

r 3

year

s (n

=95

)N

E/im

pair

ed a

t ba

selin

e an

d co

nver

ted

to d

emen

tia

(n=

47)

Art

ero

et a

l. (2

003)

obje

ct n

amin

g12

8 in

divi

dual

s w

ith

cogn

itiv

e di

ffic

ulti

esC

ogni

tive

dif

ficu

ltie

s as

cert

aine

d us

ing

the

Dét

ério

rati

onC

ogni

tive

Obs

ervé

e (D

EC

O)

scre

enin

g in

stru

men

t (R

itch

ie

& F

uhre

r, 1

992)

Iden

tifi

ed v

ia a

reg

iona

l ge

nera

l pra

ctit

ione

r ne

t-w

ork

Nam

ing

not

incl

uded

in

best

pre

dict

ive

mod

el

for

AD

.

Bei

nhof

f et

al.

(200

5)B

NT

(15

item

s)N

E (

n=

57)

MC

I: P

eter

sen

crit

eria

Mem

ory

clin

icN

E=

MD

=M

CI

> A

DM

CI

(n=

48)

AD

: NIN

CD

S-A

DR

DA

cri

teri

aA

D (

n=

66)

MD

: DSM

-IV

cri

teri

a.M

D (

n=

61)

Ben

nett

et

al. (

2002

)B

NT

(15

item

s)N

E (

n=

587)

MC

I (n

=21

1)C

ogni

tive

impa

irm

ent,

but

doe

s no

t m

eet

acce

pted

cri

teri

a fo

rde

men

tia

Cat

holic

cle

rgy

who

agr

eed

to p

arti

cipa

teB

asel

ine:

NE

> M

CI

MC

Is d

eclin

ed >

2 ti

mes

as

fas

t on

sem

anti

c m

emor

y m

easu

res

(inc

ludi

ng B

NT

)

0.85


541

Bev

ersd

orf

et a

l. (2

007)

BN

TN

E (

n=

20)

MC

I (n

=26

)M

CI:

MM

SE≥2

4, C

DR

=0.

5M

emor

y cl

inic

NE

> M

CI,

but

BN

T w

as

not

the

best

pre

dict

or0.

75

Bla

ckw

ell e

t al

. (2

004)

GN

T, s

eman

tic

batt

ery

test

(n

amin

g lin

e dr

awin

gs)

Subj

ecti

ve/o

bjec

tive

mem

ory

loss

(n

=43

), 1

1 of

who

m

deve

lope

d A

D w

ithi

n 32

m

onth

s

Nor

mal

per

form

ance

on

test

s of

la

ngua

ge a

nd v

isuo

spat

ial

func

tion

, pre

serv

ed A

DL

, C

DR

=0.

5

Mem

ory

clin

icN

onco

nver

ters

>

conv

erte

rs o

n bo

th m

easu

res

GN

T: 1

.65

Sem

anti

c B

atte

ry

test

: 1.0

8

Boz

oki e

t al

. (20

01)

BN

TIM

I (n

=48

)P

eter

sen

crit

eria

+ne

urop

sych

olog

ical

ev

iden

ce (

diag

nost

ic c

rite

ria

and

cogn

itiv

e m

easu

res

for

clin

ical

ch

ange

bas

ed o

n th

ose

prop

osed

fo

r A

AM

I)

Mic

higa

n A

lzhe

imer

’s

Dis

ease

Res

earc

h C

ente

rB

NT

dis

crim

inat

ed b

est

betw

een

conv

erte

rs a

nd

nonc

onve

rter

s,

alth

ough

not

sig

nific

ant

(p=

.16)

; 42%

of

conv

erte

rs a

nd 1

4% o

f no

ncon

vert

ers

had

abno

rmal

res

ults

Bsc

hor

et a

l. (2

001)

BN

TN

E (

n=

40)

MC

I (n

=34

)m

ild D

AT

(n

=21

)m

oder

ate

to s

ever

e D

AT

(n

=20

)

ICD

-10

crit

eria

(Z

audi

g, 1

992)

Mem

ory

Clin

ic a

t the

Dep

t.

of G

eron

tolo

gy, F

reie

U

nive

rsit

ät B

erlin

NE

> M

CI

> m

ild A

D >

m

oder

ate

AD

NE

vs.

MC

I: 1

.29

MC

I vs

. mild

AD

: 1.1

7m

ild A

D v

s. m

oder

ate

AD

: 1.1

9

Bus

se e

t al

. (20

03)

Com

posi

te a

phas

ia/

apra

xia

scor

e (n

amin

g ob

ject

s,

read

ing

and

obey

ing

a se

nten

ce, w

riti

ng

a se

nten

ce, a

nd

perf

orm

ing

a th

ree-

stag

e co

mm

and)

nond

emen

ted

elde

rly

(n=

1,04

5), 3

% o

f who

m m

et

the

crit

eria

for

MC

I-A

, 36%

MC

I-A

: Pet

erse

n cr

iter

iaA

AC

D: L

evy

(199

4) c

rite

ria

AA

CD

-m: L

evy

crit

eria

, but

no

requ

irem

ent

for

subj

ecti

ve

mem

ory

com

plai

ntD

emen

tia:

DSM

-IV

Ran

dom

sam

plin

g fr

om li

stpr

ovid

ed b

y th

e lo

cal

regi

stry

off

ice

in L

eipz

ig

No

grou

p di

ffer

ence

s;

lang

uage

sco

re n

ot a

si

gnif

ican

t pr

edic

tor

for

MM

SE≥2

6, 9

% f

or

AA

CD

and

20%

for

A

AC

D-m

Cac

capo

lo-V

an V

liet

et a

l. (2

003)

BN

TN

E (

n=

230)

QD

(n

=15

5)m

ild A

D (

n=

244)

mod

erat

e A

D (

n=

480)

seve

re A

D (

n=

376)

very

sev

ere

AD

(n=

247)

QD

: cog

niti

ve im

pair

men

t su

ffic

ient

or

clo

se t

o su

ffic

ient

for

a

diag

nosi

s of

dem

enti

a; n

o fu

ncti

onal

impa

irm

ent

AD

: NIN

CD

S-A

DR

DA

cri

teri

a

Mem

ory

Dis

orde

rs C

ente

r/re

crui

ted

for

a st

udy

of N

E.

NE

=Q

D=

mild

AD

>

mod

erat

e A

D >

sev

ere

AD

> v

ery

seve

re A

D

Che

n et

al.

(200

0)B

NT

(15

item

s)N

E (

n=

483)

Con

vert

ers

to A

D 1

.5 y

ears

af

ter

test

ing

(n=

120)

NIN

CD

S-A

DR

DA

cri

teri

aR

ando

mly

sel

ecte

d fr

om

vote

r re

gist

rati

on li

sts

NE

> in

cide

nt A

D;

how

ever

, not

a b

ette

r pr

edic

tor

of in

cide

nt

dem

enti

a th

an t

he

MM

SE

0.65

Che

n et

al.

(200

1)B

NT

(15

item

s)N

E (

n=

551)

, 68

of w

ho w

ent

on t

o de

velo

p A

DN

INC

DS-

AD

RD

A c

rite

ria

Ran

dom

ly s

elec

ted

from

vo

ter

regi

stra

tion

list

sN

onco

nver

ters

=co

nver

ters

(Con

tinu

ed)


542

AP

PE

ND

IX B

(C

ontin

ued)

Aut

hors

Tes

t us

edG

roup

s+sa

mpl

e si

zes

Dia

gnos

tic

crit

eria

R

ecru

itm

ent

proc

edur

eS

igni

fica

nt e

ffec

tsE

ffec

t si

zes

(Coh

en’s

d)

Col

lie e

t al

. (20

02)

nam

ing

of 1

5 lin

e dr

awin

gsE

lder

ly a

dult

s (n

=17

4), 2

3 of

w

hom

wer

e im

pair

ed o

n 3

cons

ecut

ive

asse

ssm

ents

CE

RA

D b

atte

ry (

Mor

ris

et a

l.,

1988

b)R

ecru

ited

fro

m a

n on

goin

g st

udy

on a

ging

at

an

inde

pend

ent

rese

arch

in

stit

ute

in M

elbo

urne

, A

ustr

alia

.

NE

> M

CI

0.77

Cro

ot e

t al

. (19

99)

Nam

ing

(as

Hod

ges

& P

atte

rson

, 199

5)N

E (

n=

46)

min

imal

AD

(n

=16

)m

ild A

D (

n=

16)

mod

erat

e A

D (

n=

14)

NIN

CD

S-A

DR

DA

cri

teri

am

inim

al: M

MSE

=24

–30

mild

: MM

SE=

18–2

3m

oder

ate:

MM

SE=

2–17

Mem

ory

Clin

ic a

t A

dden

broo

ke’s

Hos

pita

l, C

ambr

idge

p-va

lue

not

repo

rted

De

Jage

r &

Bud

ge

(200

5)G

NT

Bas

elin

e:N

E (

n=

117)

MC

I (n

=40

)3-

year

fol

low

up:

NE

(n

=85

)M

CI

(n=

49)

MC

I: >

1.5

SD

bel

ow c

ontr

ol m

ean

on m

emor

y te

stin

gT

alks

/rad

io a

dver

tisi

ng

in O

xfor

dshi

re f

or

thos

e w

ho t

houg

ht

that

the

ir h

ealt

h,

mem

ory

and

thin

king

w

ere

good

com

pare

d to

the

ir p

eers

Cla

ssif

icat

ion

at 4

yea

rs

was

pre

dict

ed b

y G

NT

De

Jage

r et

al.

(200

3)B

NT

(30

item

s)N

E (

n=

51)

MC

I (n

=29

)A

D (

n=

60)

VC

I (n

=8)

VaD

(n

=4)

MC

I: P

eter

sen

crit

eria

AD

: NIN

CD

S-A

DR

DA

cri

teri

aV

CI:

Hac

hins

ki c

rite

ria

VaD

: NIN

CD

DS/

AIR

EN

cri

teri

a (G

. Gol

d et

al.,

199

7)

Oxf

ord

Pro

ject

To

Inve

stig

ate

Mem

ory

and

Age

ing

(OP

TIM

A)

stud

y

NE

> M

CI

> A

D; C

VD

(V

CI+

VaD

) al

so

exhi

bite

d im

pair

men

ts

NE

vs.

MC

I: 0

.54

MC

I vs

. AD

: 1.1

5N

E v

s. C

VD

: 0.8

9

Dev

anan

d et

al.

(199

7)B

NT

QD

(n=

62),

26

of w

hom

wen

t on

to

deve

lop

dem

enti

aQ

D: c

ogni

tive

impa

irm

ent,

fal

l be

twee

n “n

orm

al”

and

“dem

enti

a” c

ateg

orie

sD

emen

tia:

DSM

-III

cri

teri

aA

D: N

INC

DS-

AD

RD

A

crit

eria

Mem

ory

Dis

orde

rs C

linic

No

sign

ific

ant

effe

cts

Dud

as e

t al

. (20

05)

Nam

ing

Tes

t (H

odge

s et

al.,

19

92b)

and

GN

T

NE

(n

=29

)M

CI

(n=

24)

AD

(n

=22

)

Pet

erse

n cr

iter

iaM

emor

y C

linic

at

Add

enbr

ooke

’s

Hos

pita

l, C

ambr

idge

NE

> M

CI=

AD

Nam

ing:

NE

vs.

MC

I, 1

.42;

MC

I vs

. AD

, 0.6

4G

NT

:N

E v

s. M

CI,

0.6

3; M

CI

vs. A

D, 1

.20

Dw

olat

zky

et a

l. (2

003)

BN

TN

E (

n=

15)

MC

I (n

=20

)A

D (

n=

19)

Pet

erse

n cr

iter

iaM

emor

y cl

inic

sB

NT

dis

crim

inat

ed

betw

een

MC

I an

d he

alth

y el

derl

y


543

Fill

enba

um e

t al

. (2

005)

BN

T (

15 it

ems)

NE

: n=

201

(Sea

ttle

), n

=12

0 (H

awai

i)C

DR

=0.

5: n

=33

(Se

attl

e),

n=

65 (

Haw

aii)

CD

R=

1: n

=37

(Se

attl

e),

n=

97 (

Haw

aii)

CD

R=

2: n

=33

(Se

attl

e),

n=

55 (

Haw

aii)

CD

R=

3,4,

5: n

=46

(Se

attl

e),

n=

81 (

Haw

aii)

CD

R s

core

Seat

tle:

Kin

g C

ount

y te

leph

one

dire

ctor

ies,

H

ealt

h C

are

Fin

anci

ng

Adm

inis

trat

ion

(now

C

MS)

Med

icar

e re

cipi

ent

lists

, Ja

pane

se-A

mer

ican

or

gani

zati

onal

list

s, a

nd

wor

d of

mou

thH

awai

i: Ja

pane

se-A

mer

ican

m

en b

orn

1900

–191

9,

livin

g in

Oah

u in

196

5,

who

had

bee

n on

the

W

orld

War

II

Sele

ctiv

e Se

rvic

e R

egis

trat

ion

file

CD

R 0

< C

DR

0.5

in

both

pop

ulat

ions

Fle

ishe

r et

al.

(200

7)B

NT

(10

item

s)M

CI-

A w

ho p

rogr

esse

d to

A

D w

ithi

n 36

mon

ths

(n=

212)

Pet

erse

n cr

iter

iaP

arti

cipa

nts

in a

36-

mon

th

rand

omiz

ed d

rug

tria

lB

NT

was

not

a m

easu

re

in t

he m

odel

tha

t w

as

mos

t pr

edic

tive

of

prog

ress

ion

to A

DF

licke

r et

al.

(199

1)ob

ject

nam

ing

NE

(n

=32

)M

ildly

impa

ired

(n

=32

)G

DS

rati

ng o

f 3

Sele

cted

fro

m p

arti

cipa

nts

in a

ging

stu

dies

at

the

Agi

ng a

nd D

emen

tia

Res

earc

h C

ente

r, N

YU

M

edic

al C

ente

r

NE

> M

ildly

impa

ired

0.79

Gal

vin

et a

l. (2

005)

BN

TN

E (

n=

80)

who

eve

ntua

lly

cam

e to

aut

opsy

CD

R s

core

Indi

vidu

als

enro

lled

in lo

ngit

udin

al s

tudi

es

of h

ealt

hy a

ging

and

de

men

tia

Bas

elin

e: d

emen

tia

=no

de

men

tia

Fin

al e

xam

inat

ion:

no

dem

enti

a >

dem

enti

a

1.32

Gal

ton

et a

l. (2

005)

PN

(C

ambr

idge

Se

man

tic

Bat

tery

, H

odge

s &

P

atte

rson

, 199

5)G

NT

QD

(n

=31

) 11

of

who

m h

ad

conv

erte

d to

AD

at

24.2

m

onth

s

AD

: NIN

CD

S-A

DR

DA

cri

teri

aQ

D: s

ubje

ctiv

e m

emor

y im

pair

men

t,

corr

obor

ated

by

an in

form

ant;

no

rmal

AD

L; M

MSE

≥ 2

3.

CD

R=

0.5.

Mem

ory

Clin

ic a

t A

dden

broo

ke’s

H

ospi

tal,

Cam

brid

ge

PN

: AD

< n

onco

nver

ters

GN

T: A

D <

con

vert

ers

<

nonc

onve

rter

s

PN

: Non

conv

erte

rs v

s.

AD

, 1.4

0G

NT

:N

onco

nver

ters

vs.

co

nver

ters

, 2.1

8C

onve

rter

s vs

. AD

, 0.

76

AD

(n

=19

)

Ges

lani

et

al. (

2005

)B

NT

(od

d-ev

en

vers

ion)

MC

Is (

n=

161)

Pet

erse

n cr

iter

ia+

corr

obor

atio

n of

m

emor

y de

fici

t by

phy

sici

anR

efer

red

by p

rim

ary-

care

ph

ysic

ians

Ave

rage

scor

e: 3

2.8

± 9.

44

(no

com

pari

son

grou

p)G

oldm

an e

t al

. (2

001)

BN

TN

E (

n=

9)

prec

linic

al A

D (

n=

5)C

linic

ally

non

dem

ente

d, b

ut

neur

itic

and

dif

fuse

pla

ques

th

roug

hout

the

neo

cort

ex

(aut

opsy

fin

ding

s)

Was

hing

ton

Uni

vers

ity’

s A

lzhe

imer

’s d

isea

se

Res

earc

h C

entr

e

NE

=pr

eclin

ical

AD

>

very

mild

AD

Pre

clin

ical

AD

vs.

ver

y m

ild A

D: 1

.1A

D (

n=

10)

(Con

tinu

ed)


544

AP

PE

ND

IX B

(C

ontin

ued)

Aut

hors

Tes

t us

edG

roup

s+sa

mpl

e si

zes

Dia

gnos

tic

crit

eria

R

ecru

itm

ent

proc

edur

eS

igni

fica

nt e

ffec

tsE

ffec

t si

zes

(Coh

en’s

d)

Góm

ez &

Whi

te

(200

6)B

NT

NE

(n

=76

)N

E: C

DR

=0

Med

ia a

ppea

ls a

nd

pres

enta

tion

s by

re

sear

cher

s

NE

> v

ery

mild

AD

0.77

very

mild

AD

(n

=77

)ve

ry m

ild A

D: N

INC

DS-

AD

RD

A

& D

SM-I

II c

rite

ria;

CD

R=

0.5

Gri

ffit

h et

al.

(200

6)B

NT

(15

item

s)N

E (

n=

49)

Pet

erse

n cr

iter

iaM

emor

y D

isor

ders

Clin

ic

or r

ecru

ited

fro

m

com

mun

ity

NE

=M

CI

MC

I (n

=49

)

Gru

ndm

an e

t al

. (2

004)

BN

T (

15 it

ems)

NE

(n

=10

7)P

eter

sen

crit

eria

+C

DR

=0.

5A

dver

tisi

ng c

ampa

ign

targ

etin

g el

derl

y su

bjec

ts in

cit

ies

wit

h A

lzhe

imer

Dis

ease

C

oope

rati

ve S

tudy

(A

DC

S) s

ites

NE

> M

CI

0.51

MC

I (n

=76

9)

Gua

rch

et a

l. (2

004)

BN

TN

E (

n=

34)

Subj

ecti

ve m

emor

y lo

ss;

neur

opsy

chol

ogic

al t

ests

not

use

d as

incl

usio

n/ex

clus

ion

crit

eria

.

Clin

ical

psy

chol

ogy

serv

ice

at t

he H

ospi

tal C

linic

i P

rovi

ncia

l, B

arce

lona

.

NE

> S

ML

NE

vs.

SM

L: 0

.89

SML

(n

=43

), 1

0 of

who

m

wen

t on

to

deve

lop

AD

SML

: bas

al=

rete

stN

onco

nver

ters

vs.

co

nver

ters

, ret

est:

1.

56ba

sal:

nonc

onve

rter

s=

conv

erte

rsre

test

: non

conv

erte

rs >

co

nver

ters

Hod

ges,

E

rzin

çlio

glu,

&

Pat

ters

on (

2006

)

nam

ing

64 li

ne

draw

ings

NE

(n

=24

)G

rund

man

et

al. (

2004

) cr

iter

iaM

emor

y C

linic

at

Add

enbr

ooke

’s

Hos

pita

l, C

ambr

idge

NE

=M

CI-

A e

ven

afte

r 7

year

s of

fol

low

-up

MC

I-A

(n

=10

)

Hod

ges

& P

atte

rson

(1

995)

nam

ing

64 li

ne

draw

ings

NE

(n

=24

)N

INC

DS-

AD

RD

A c

rite

ria

Mem

ory

Clin

ic a

t A

dden

broo

ke’s

H

ospi

tal,

Cam

brid

ge

NE

> m

inim

al=

mild

>

mod

erat

em

inim

al A

D (

n=

17)

mild

AD

(n

=17

), m

oder

ate

AD

(n

=18

)H

odge

s et

al.

(199

6)N

amin

g of

48

line

draw

ings

N

E (

n=

10)

AD

: NIN

CD

S-A

DR

DA

cri

teri

aM

emor

y C

linic

at

Add

enbr

ooke

’s

Hos

pita

l, C

ambr

idge

NE

> m

inim

al=

mild

>

mod

erat

em

inim

al A

D (

n=

16)

min

imal

: MM

SE=

24–3

0m

ild A

D (

n=

17)

mild

: MM

SE=

18–2

3m

oder

ate

AD

(n

=18

)m

oder

ate:

MM

SE=

2–17

Hud

on e

t al

. (20

06)

Dén

omin

atio

n or

ale

d’im

ages

(D

eloc

he &

H

anne

quin

, 199

7)

NE

(n

=22

)M

CI:

MC

I-SD

/MC

I-M

D, P

eter

sen

(200

4) c

rite

ria

Mem

ory

clin

ics

NE

=M

CI

> A

DN

E v

s. A

D: 0

.88

MC

I (n

=14

)M

CI

vs. A

D: 0

.72

AD

(n

=14

)


545

Jaco

bs e

t al

. (19

95)

BN

T (

15 it

ems)

nond

emen

ted

elde

rly

(n=

443)

, 41

of

who

m h

ad d

evel

oped

A

D a

t fo

llow

-up

(on

aver

age

2.05

yea

rs la

ter)

NIN

CD

S-A

DR

DA

cri

teri

aN

orth

Man

hatt

an

Agi

ng P

roje

ct, a

co

mm

unit

y-ba

sed,

ep

idem

iolo

gic

stud

y of

de

men

tia

in n

orth

ern

Man

hatt

an, N

Y.

BN

T s

igni

fica

ntly

as

soci

ated

wit

h in

crea

sed

risk

of

deve

lopi

ng A

D.

Jaco

bson

et

al.

(200

2)B

NT

NE

(n

=20

)pr

eclin

ical

AD

: eit

her m

ild su

bjec

tive

m

emor

y co

mpl

aint

s w

itho

ut

func

tion

al im

pair

men

t (n

=9)

or

an

abno

rmal

ity

in t

he

part

icip

ant’

s ne

urol

ogic

al

exam

inat

ion

(n=

11).

Did

not

m

eet

NIN

CD

S-A

DR

DA

cri

teri

a fo

r A

D

Alz

heim

er’s

Dis

ease

R

esea

rch

Cen

ter

at

UC

SD.

Bes

t pr

edic

tor

was

di

ffer

ence

sco

res

betw

een

nam

ing

(BN

T)

and

visu

ocon

stru

ctio

n ab

iliti

es (

WA

IS B

lock

de

sign

), n

ot r

aw B

NT

sc

ore;

10/

20 p

recl

inic

al

AD

indi

vidu

als

and

5/20

con

trol

s ha

d as

ymm

etri

c pr

ofile

s

prec

linic

al A

D (

n=

20)

Kar

rasc

h et

al.

(200

5)C

ER

AD

nam

ing

subt

est

NE

(n

=15

)P

eter

sen

crit

eria

Com

mun

ity

sour

ces

NE

> A

D, n

ot M

CI

MC

I (n

=15

)A

D (

n=

15)

Lam

bon

Ral

ph e

t al.

(200

3)na

min

g 64

line

dr

awin

gsN

E (

n=

48)

Subj

ecti

ve m

emor

y im

pair

men

t,

corr

obor

ated

by

a sp

ouse

/fam

ily

mem

ber;

pre

serv

atio

n of

AD

L;

impa

irm

ent

on a

t le

ast

one

test

of

mem

ory;

nor

mal

per

form

ance

on

test

s of

lang

uage

, vis

uosp

atia

l and

ex

ecut

ive

func

tion

; MM

SE >

24.

Mem

ory

Clin

ic a

t A

dden

broo

ke’s

H

ospi

tal,

Cam

brid

ge

NE

=M

CI

MC

I (n

=17

)m

ild A

D (

n=

22)

mod

erat

e A

D (

n=

8)se

vere

AD

(n

=8)

Lee

et

al. (

2006

)B

NT

(15

item

s)Q

D (n

=72

), 1

4 of

who

m

prog

ress

ed t

o A

D in

3 y

ears

CD

R=

0.5

One

pub

lic h

ealt

h ce

nter

an

d 2

mem

ory

clin

ics

in

Kor

ea

Non

conv

erte

rs=

conv

erte

rs

Lóp

ez e

t al

. (20

06)

BN

TN

E (

n=

374)

MC

I-A

: >1.

5 SD

s be

low

con

trol

s in

de

laye

d re

call

+de

clin

e in

co

gnit

ive

func

tion

ing;

M

CI-

MD

>1.

5 SD

s in

at

leas

t on

e co

gnit

ive

dom

ain

othe

r th

an

mem

ory/

one

abno

rmal

tes

t in

≥2

dom

ains

.

5201

non

inst

itut

iona

lized

in

divi

dual

s ov

er 6

5;

recr

uite

d fr

om f

our

com

mun

itie

s us

ing

Par

t A

Med

icar

e lis

t in

198

8–19

89; 6

87

Afr

ican

-Am

eric

ans

recr

uite

d in

sam

e m

anne

r in

199

2–19

93

NE

> M

CI-

A >

M

CI-

MD

NE

vs.

MC

I-A

: 0.1

9M

CI-

A (

n=

10)

NE

vs.

MC

I-M

D: 1

.40

MC

I-M

D (

n=

28)

MC

I-M

D v

s. M

CI-

A:

0.92

Mio

shi e

t al

. (20

06)

PN

(C

ambr

idge

Se

man

tic

Bat

tery

, H

odge

s &

P

atte

rson

, 199

5)G

NT

NE

(n

=63

)M

CI

(n=

36)

AD

(n

=67

)D

LB

(n

=20

)F

TD

(n

=55

)

MC

I: G

rund

man

et

al. (

2004

) cr

iter

iaA

D: N

INC

DS-

AD

RD

A c

rite

ria

DL

B: M

cKei

th e

t al

. (20

00)

FT

D: N

eary

et

al. (

1998

)

Mem

ory

Clin

ic, E

arly

O

nset

Dem

enti

a C

linic

an

d D

rug

Mon

itor

ing

Clin

ic a

t A

dden

broo

ke’s

H

ospi

tal

NE

> M

CI

> d

emen

tia

NE

vs.

MC

I, 0

.77;

MC

I vs

. dem

enti

a, 0

.77

(Con

tinu

ed)


546

AP

PE

ND

IX B

(C

ontin

ued)

Aut

hors

Tes

t us

edG

roup

s+sa

mpl

e si

zes

Dia

gnos

tic

crit

eria

Rec

ruit

men

t pr

oced

ure

Sig

nifi

cant

eff

ects

Eff

ect

size

s (C

ohen

’s d

)

Mor

ris

et a

l. (2

001)

BN

TN

E (

n=

177)

uAD

(n

=53

)iA

D (n

=69

)A

D (

n=

105)

NE

: CD

R=

0R

ecru

ited

thr

ough

the

m

edia

NE

> u

AD

> iA

D >

AD

NE

vs.

iAD

: 0.4

4uA

D v

s. iA

D: 0

.25

iAD

vs.

AD

: 0.2

4M

CI:

CD

R=

0.5

uAD

: CD

R=

0.5

iAD

: CD

R=

0.5

AD

: CD

R=

0.5;

clin

ical

cr

iter

ia d

escr

ibed

in M

orri

s,

McK

eel,

Ful

ling,

Tor

ack

&

Ber

g, 1

988a

Nes

tor

et a

l. (2

003)

64-i

tem

nam

ing

test

(B

ozea

t et

al.,

20

00)

Con

trol

s (n

=15

), M

CIs

(n

=10

); A

Ds

(n=

10)

MC

I: in

sidi

ous

onse

t m

emor

y sy

mpt

oms,

obj

ecti

ve m

emor

y im

pair

men

t, n

o ot

her

sign

ific

ant

defi

cits

Mem

ory

Clin

icM

CI

> A

D

AD

: NIN

CD

S-A

DR

DA

cri

teri

aN

iels

en e

t al

. (19

99)

Nam

ing

subt

est

of

CA

MC

OG

Non

dem

ente

d el

derl

y (n

=2,

452)

, 102

of

who

m

deve

lope

d de

men

tia

in

2 ye

ars

DSM

-III

-R c

rite

ria,

N

INC

DS-

AD

RD

A c

rite

ria

Ran

dom

ly d

raw

n fr

om t

he

popu

lati

onN

onde

men

ted

> in

cide

nt

dem

ente

d0.

83

Nor

dlun

d et

al.

(200

5)B

NT

NE

(n

=35

)Su

bjec

tive

and

obj

ecti

ve m

emor

y im

pair

men

t >

6 m

onth

s;

posi

tive

out

com

e on

ste

pwis

e co

mpa

rati

ve s

tatu

s an

alys

is

(ST

EP

, Wal

lin e

t al

., 19

96),

I-

Fle

x (R

oyal

l et

al.,

1992

),

MM

SE o

r C

DR

; MM

SE ≥

25;

not

mor

e th

an 2

+ve

ou

tcom

es o

n ST

EP

Mem

ory

clin

icN

E >

MC

Is0.

60M

CI

(n=

109)

Pet

erse

n et

al.

(199

9)B

NT

NE

(n

=23

4)M

CI:

mem

ory

com

plai

nt; n

orm

al

AD

L; n

orm

al g

ener

al c

ogni

tive

fu

ncti

on; a

bnor

mal

mem

ory

for

age;

not

dem

ente

d; C

DR

=0.

5.m

ild A

D: C

DR

=0.

5–1.

0

Com

mun

ity

(sub

ject

s re

ceiv

ing

gene

ral

med

ical

car

e at

May

o C

linic

) A

ND

reg

iona

l (e

valu

atio

n of

cog

niti

ve

diff

icul

ties

at

May

o A

lzhe

imer

’s D

isea

se

Cen

ter)

NE

> M

CI

> A

DN

E v

s. M

CI:

7.2

MC

I (n

=76

)M

CI

vs. A

D (

CD

R

0.5)

: 6.7

8m

ild A

D (

n=

106)

Pyo

et

al. (

2006

)A

DA

S-C

og N

amin

g O

bjec

ts a

nd

Fin

gers

test

NE

(n

=84

3)M

CI:

CD

R=

0.5,

mem

ory

loss

but

no

dem

enti

aM

edia

app

eals

NE

> M

CI

> A

D (

CD

R

0.5)

> A

D (

CD

R 1

)N

E v

s. M

CI:

1.0

4un

cert

ain/

MC

I (n

=13

5)M

CI

vs. A

D (

CD

R

0.5)

: 0.0

9A

D (

CD

R 0

.5 v

s. 1

):

0.23

AD

, CD

R=

0.5

(n=

30)

AD

, CD

R=

1 (n

=12

5)


547

Rib

eiro

et

al. (

2006

)O

bjec

t na

min

g te

st

from

the

Bat

tery

of

Lis

bon

for

the

Ass

essm

ent

of

Dem

enti

a

NE

(n

=63

)su

bjec

tive

mem

ory

com

plai

nts;

≥1.

5 S

D b

elow

nor

mal

on

dela

yed

reca

ll; p

rese

rved

act

ivit

ies

of d

aily

liv

ing;

mai

ntai

ned

prof

essi

onal

, so

cial

and

fam

ilial

act

ivit

ies

acco

rdin

g to

clin

ical

judg

men

t A

ND

sco

re <

3 on

the

fir

st p

art

of

the

Ble

ssed

Dem

enti

a Sc

ale;

pr

eser

ved

gene

ral c

ogni

tive

fu

ncti

on.

Dem

enti

a O

utpa

tien

t C

linic

, Hos

pita

l San

ta

Mar

ia, a

nd a

Mem

ory

Clin

ic, L

isbo

n

NE

=M

CI

MC

I (n

=11

6)

Ric

hard

s et

al.

(199

9)N

amin

g of

10

obje

cts

(EC

O)

111

indi

vidu

als,

cla

ssif

ied

as

NE

(n

=74

), A

AM

I (n

=37

),

or A

AC

D (

n=

39).

AA

MI:

mem

ory

impa

irm

ent,

no

dem

enti

aA

AC

D: i

mpa

irm

ent

in o

ne

dom

ain:

mem

ory/

lear

ning

, at

tent

ion/

con

cent

rati

on,

visu

ospa

tial

rea

soni

ng, l

angu

age,

vi

suos

pati

al f

unct

ion

Ran

dom

ly r

ecru

ited

fro

m

600

gene

ral m

edic

al p

rac-

tice

s in

sou

ther

n F

ranc

e

NE

> A

AC

DN

E v

s. A

AC

D: 0

.79

NE

=A

AM

I

Rub

in e

t al

. (19

98)

BN

TN

E (

n=

82),

10

of w

hom

wen

t on

to

deve

lop

AD

, 6 iA

D,

and

11 u

ncer

tain

dem

enti

a

CD

R >

0R

ecru

ited

fro

m t

he

com

mun

ity

BN

T d

iscr

imin

ated

be

twee

n D

AT

/ID

AT

an

d N

E, b

ut o

nly

afte

r di

agno

sis

of d

emen

tia

Saxt

on e

t al

. (20

04)

BN

TN

onde

men

ted

elde

rly

(n=

693)

, 72

of w

hom

de

velo

ped

AD

wit

hin

1.5–

8 ye

ars

(1.5

–3.4

yea

rs: n

=24

; 3.

5–5.

0 ye

ars:

n=

20; 5

.1–8

.1

year

s: n

=28

)

NIN

CD

S-A

DR

DA

cri

teri

aSe

lect

ed f

rom

par

tici

pant

s re

crui

ted

from

the

co

mm

unit

y as

par

t of t

he

Car

diov

ascu

lar

Hea

lth

Stud

y

Sign

ific

ant

pred

icto

r of

A

D u

p to

3.5

yea

rs

prio

r to

dia

gnos

is

Schm

idtk

e &

H

erm

enei

t (20

07)

CE

RA

D n

amin

gM

CI

(n=

88),

75

of w

hom

w

ere

avai

labl

e fo

r fo

llow

-up

Pet

erse

n cr

iter

iaM

emor

y C

linic

Non

conv

erte

rs=

conv

erte

rs

Smal

l et

al. (

2000

)N

amin

g su

bsec

tion

of

Sw

edis

h M

MSE

Non

dem

ente

d el

derl

y (n

=56

9), 7

3 of

who

m w

ent

on t

o de

velo

p A

D

DSM

-III

-RSu

bjec

ts p

arti

cipa

ting

in

Kun

gsho

lmen

pro

ject

w

ho w

ere

not

dem

ente

d at

fir

st f

ollo

w-u

p (s

ee S

mal

l et

al.,

1997

)

Non

conv

erte

rs=

conv

erte

rs

Swai

nson

et

al.

(200

1)G

NT

New

sem

anti

c ba

tter

y na

min

g te

st

NE

(n

=39

)Q

D (

n=

43)

mild

AD

(n

=26

)M

D (

n=

37)

AD

: NIN

CD

S-A

DR

DA

cri

teri

aM

D: D

SM-I

VQ

D: m

emor

y im

pair

men

t bu

t no

t m

eeti

ng c

rite

ria

for

dem

enti

a or

de

pres

sion

Mem

ory

clin

ic,

Add

enbr

ooke

’s

Hos

pita

l; P

sych

iatr

y D

epar

tmen

t, W

est

Suff

olk

Hos

pita

l; M

enta

l Hea

lth

Serv

ices

, A

dden

broo

ke’s

NH

S T

rust

AD

< Q

D+

MD

+N

E o

n bo

th m

easu

res

QD

< M

D+

NE

on

sem

anti

c na

min

gN

o si

gnif

ican

t co

rrel

atio

n be

twee

n ba

selin

e pe

rfor

man

ce

and

MM

SE d

eclin

e in

Q

D in

divi

dual

s

(Con

tinu

ed)


548

AP

PE

ND

IX B

(C

ontin

ued)

Aut

hors

Tes

t us

edG

roup

s+sa

mpl

e si

zes

Dia

gnos

tic

crit

eria

R

ecru

itm

ent

proc

edur

eS

igni

fica

nt e

ffec

tsE

ffec

t si

zes

(Coh

en’s

d)

Tab

ert

et a

l. (2

006)

BN

T (

15-i

tem

ve

rsio

n)N

E (

n=

83)

Age

≥40

; cog

niti

ve im

pair

men

t fo

r 6

mon

ths-

10 y

ears

; CD

R 0

–0.5

.F

or m

emor

y: M

MSE

, SR

T,

WA

IS–R

per

form

ance

IQ

.If

no

form

al c

ogni

tive

def

icit

: su

bjec

tive

mem

ory

decl

ine,

po

siti

ve s

core

on

1 or

mor

e of

the

fi

rst

8 it

ems

of t

he m

odif

ied

Ble

ssed

Fun

ctio

nal A

ctiv

ity

Scal

e.

Mem

ory

diso

rder

s cl

inic

; N

E r

ecru

ited

by

adve

rtis

emen

t

NE

> M

CI

NE

vs.

MC

I: 0

.43

MC

I (n

=14

8)no

ncon

vert

ers

>

conv

erte

rsN

onco

nver

ters

vs.

co

nver

ters

: 0.6

7

Tes

ta e

t al

. (20

04)

BN

TN

E (

n=

409)

cons

ensu

s am

ong

beha

vior

al

neur

olog

ists

, clin

ical

ne

urop

sych

olog

ists

, nur

ses,

and

ps

ycho

met

rist

s; C

DR

& D

RS

Com

mun

ity

(sub

ject

s re

ceiv

ing

gene

ral m

edic

al

care

at

May

o C

linic

) A

ND

May

o A

lzhe

imer

’s

Dis

ease

Cen

ter)

Non

dem

ente

d >

inci

dent

A

D, b

ut n

o ad

ded

diag

nost

ic u

tilit

y on

ce

dela

yed

reca

ll ef

fect

s in

clud

ed in

the

mod

el

MC

Is (

n=

67)

AD

s (n

=30

6)

Tho

mps

on e

t al

. (2

002)

GN

TN

E (

n=

31)

qAD

: com

plai

nts

of e

piso

dic

mem

ory

impa

irm

ent

but

no

dem

enti

aA

D: N

INC

DS-

AD

RD

A c

rite

ria

Mem

ory

Clin

ic a

t A

dden

broo

ke’s

H

ospi

tal,

Cam

brid

ge

GN

T: N

E=

qAD

> A

DG

FN

TqA

D (

n=

28)

GF

NT

: NE

> q

AD

> A

DA

D (

n=

31)

6 of

7 c

onve

rter

s at

1–2

ye

ars

show

ed

impa

irm

ent

on G

FN

T;

17 o

f 21

non

conv

erte

rs

scor

ed n

orm

ally

Tou

chon

& R

itch

ie

(199

9)ob

ject

nam

ing

subt

est

of E

CO

NE

(n

=15

0)de

men

tia:

DSM

-III

-R A

D:

NIN

CD

S-A

DR

DA

cri

teri

aG

ener

al p

ract

itio

ner

recr

uitm

ent

netw

ork

Nam

ing

not

a pr

edic

tor

of in

cide

nt d

emen

tia

2 ye

ars

prio

r to

ons

etno

ndem

ente

d el

derl

y (n

=35

9),

22 o

f w

hom

dev

elop

ed A

D

in 3

rd y

ear

Vog

el e

t al

. (20

05)

Nam

ing

of 3

0 co

lore

d lin

e dr

awin

gs o

f co

mm

on o

bjec

ts in

6

cate

gori

es

NE

(n

=58

)A

D: N

INC

DS-

AD

RD

A c

rite

ria

Rec

ruit

ed f

rom

ref

erra

ls t

o th

e C

open

hage

n U

nive

rsit

y H

ospi

tal

Mem

ory

Clin

ic

NE

=pr

edem

enti

a A

D >

A

Dpr

edem

enti

a A

D (

n=

22)

pred

emen

tia

AD

: Pet

erse

n cr

iter

ia+

subs

eque

nt p

rogr

essi

on

to A

D (

10–3

0 m

onth

s la

ter)

mild

AD

(n

=10

2)

Not

e. E

ffec

t si

zes

are

repo

rted

whe

re p

ossi

ble.

AA

CD

=ag

e-as

soci

ated

cog

niti

ve d

eclin

e. A

AC

D-m

=ag

e-as

soci

ated

cog

niti

ve d

eclin

e—m

odif

ied.

AA

MI=

age-

asso

ciat

ed m

emor

y im

pair

men

t.A

D=

Alz

heim

er’s

dis

ease

. B

NT

=B

osto

n N

amin

g T

est.

CA

MC

OG

= C

ambr

idge

Cog

niti

ve E

xam

inat

ion.

CD

R=

Clin

ical

Dem

enti

a R

atin

g Sc

ale.

CE

RA

D=

Con

sort

ium

to

Est

ablis

h a

Reg

istr

y fo

rA

lzhe

imer

’s D

isea

se.

CV

D=

cere

brov

ascu

lar

dise

ase.

EC

O =

Eva

luat

ion

Cog

niti

ve p

ar O

rdin

ateu

r [C

ompu

teri

zed

Cog

niti

ve E

valu

atio

n].

FT

D=

fron

tote

mpo

ral

dem

enti

a. G

FN

T=

Gra

ded

Fac

esT

est,

nam

ing

com

pone

nt. G

NT

=G

rade

d N

amin

g T

est.

iAD

=in

cipi

ent

AD

. IM

I=is

olat

ed m

emor

y im

pair

men

t. L

BD

=L

ewy

body

dem

enti

a. M

CI=

mild

cog

niti

ve im

pair

men

t. M

CI-

A=

MC

I-am

nest

ic.

MC

I-M

D=

MC

I-m

ulti

ple

dom

ain.

MC

I-SD

=M

CI-

sing

le d

omai

n. M

D=

maj

or d

epre

ssio

n. M

MSE

=M

ini

Men

tal

Stat

e E

xam

inat

ion.

NE

=no

rmal

eld

erly

. N

INC

DS-

AD

RD

A=

Nat

iona

l In

stit

ute

ofN

euro

logi

cal

and

Com

mun

icat

ive

Dis

orde

rs.

PN

=pi

ctur

e na

min

g. q

AD

=qu

esti

onab

le A

D.

QD

=qu

esti

onab

le d

emen

tia.

SM

L=

subj

ecti

ve m

emor

y lo

ss.

STE

P =

Ste

pwis

e C

ompa

rati

ve S

tatu

sA

naly

sis.

SR

T =

Bus

cke

Sele

ctiv

e R

emin

ding

Tes

t. u

AD

=un

cert

ain

AD

. VaD

=va

scul

ar d

emen

tia.

VC

I=va

scul

ar c

ogni

tive

impa

irm

ent.

WA

IS-R

=W

echs

ler

Adu

lt I

ntel

ligen

ce S

cale

–Rev

ised

.


549

AP

PE

ND

IX C

Pub

lishe

d st

udie

s re

port

ing

perf

orm

ance

of M

CI a

nd p

recl

inic

al A

D in

divi

dual

s on

sta

ndar

dize

d te

sts

othe

r th

an v

erba

l flu

ency

or

nam

ing

Aut

hors

Tes

t us

edG

roup

s+sa

mpl

e si

zes

Dia

gnos

tic

crit

eria

Rec

ruit

men

t pr

oced

ure

Sig

nifi

cant

eff

ects

Eff

ect

size

s

Adl

am e

t al

. (20

06)

Wor

d–pi

ctur

e m

atch

ing;

co

ncre

te &

abs

trac

t w

ord

syno

nym

tes

t (W

arri

ngto

n et

al.,

19

98)

NE

(n

=30

)M

CI

(n=

10)

mild

AD

(n

=11

)

MC

I: P

eter

sen

crit

eria

AD

: N

INC

DS-

AD

RD

A c

rite

ria

Mem

ory

Clin

ic a

t A

dden

broo

ke’s

H

ospi

tal,

Cam

brid

ge

NE

=M

CI

> A

D o

n al

l tas

ksM

CI

vs. A

D: w

ord–

pict

ure

mat

chin

g, 1

.14

conc

rete

wor

d sy

nony

m t

est,

1.

07ab

stra

ct w

ord

syno

nym

tes

t,

0.54

Agg

arw

al e

t al

. (2

005)

ER

VT

(15

item

s;

Eks

trom

et

al.,

1976

)M

CI

(n=

218)

, 82

of

who

m d

evel

oped

AD

MC

I: C

ogni

tive

impa

irm

ent

but

do n

ot m

eet

NIN

CD

S–A

DR

DA

cri

teri

a fo

r de

men

tia

Cat

holic

cle

rgy

who

ag

reed

to

part

icip

ate

Red

uced

sem

anti

c m

emor

y (c

ompo

site

sco

re o

f B

NT

, E

xten

ded

Ran

ge

Voc

abul

ary,

NA

RT

) pr

edic

ted

AD

(re

lati

ve

risk

=0.

62);

how

ever

, ep

isod

ic m

emor

y im

pair

men

t st

rong

er

pred

icto

r

NA

RT

(20

item

s;

Nel

son,

198

2)A

D: N

INC

DS-

AD

RD

A

crit

eria

Art

ero

et a

l. (2

003)

Wor

d an

d sy

ntax

com

preh

ensi

on12

8 in

divi

dual

s w

ith

cogn

itiv

e di

ffic

ulti

esC

ogni

tive

dif

ficu

ltie

s as

cert

aine

d us

ing

the

Det

erio

rati

onC

ogni

tive

Obs

ervé

e (D

EC

O)

scre

enin

g in

stru

men

t (R

itch

ie &

Fuh

rer,

199

2)

Iden

tifi

ed v

ia a

reg

iona

l ge

nera

l pra

ctit

ione

r ne

twor

k

Wor

d an

d sy

ntax

co

mpr

ehen

sion

not

in

clud

ed in

bes

t pr

edic

tive

mod

el f

or A

D

Ben

nett

et

al. (

2002

)C

ompl

ex id

eati

onal

m

ater

ial,

ER

VT

NA

RT

NE

(n

=58

7)M

CI

(n=

211)

Cog

niti

ve im

pair

men

t, b

ut

does

not

mee

t ac

cept

ed

crit

eria

for

dem

enti

a

Cat

holic

cle

rgy

who

ag

reed

to

part

icip

ate

Com

posi

te s

core

of

sem

anti

c m

emor

y: N

E >

MC

IR

ate

of d

eclin

e: M

CI

> N

E

ER

VT

: 0.4

6N

AR

T: 0

.42

Bla

ckw

ell e

t al

. (2

004)

NA

RT

Subj

ecti

ve/ o

bjec

tive

m

emor

y lo

ss (n

=43

),

11 o

f w

hom

de

velo

ped

AD

w

ithi

n 32

mon

ths

norm

al p

erfo

rman

ce o

n te

sts

of la

ngua

ge a

nd

visu

ospa

tial

fun

ctio

n,

pres

erve

d ac

tivi

ties

of

daily

life

, CD

R=

0.5

Mem

ory

clin

icN

onco

nver

ters

=co

nver

ters

Bsc

hor

et a

l. (2

001)

Coo

kie

The

ft P

ictu

reN

E (n

=40

)M

CI

(n=

34)

mild

AD

(n

=21

)m

oder

ate

to s

ever

e A

D

(n=

20)

ICD

-10

crit

eria

(Z

audi

g,

1992

)M

emor

y cl

inic

, Dep

t. o

f G

eron

tolo

gy, F

reie

U

nive

rsit

ät B

erlin

NE

/MC

I >

AD

on

“per

sons

an

d ob

ject

s”, l

ocal

izat

ions

, A

ctio

ns a

nd S

um o

f m

easu

res

(Con

tinu

ed)


550

AP

PE

ND

IX C

(C

ontin

ued)

Aut

hors

Tes

t us

edG

roup

s+sa

mpl

e si

zes

Dia

gnos

tic

crit

eria

Rec

ruit

men

t pr

oced

ure

Sig

nifi

cant

eff

ects

Eff

ect

size

s

Bus

se e

t al

. (20

03)

Com

posi

te a

phas

ia/

apra

xia

scor

e (n

amin

g ob

ject

s,

read

ing

and

obey

ing

a se

nten

ce, w

riti

ng a

se

nten

ce, a

nd

perf

orm

ing

a th

ree-

stag

e co

mm

and)

nond

emen

ted

elde

rly

(n=

1045

), 3

% o

f w

hom

met

the

crit

eria

for

MC

I-A

, 36

% fo

r M

MSE

≥26,

9%

for

AA

CD

and

20

% fo

r A

AC

D-m

MC

I-A

: Pet

erse

n cr

iter

iaA

AC

D: L

evy

(199

4) c

rite

ria

AA

CD

-m: L

evy

crit

eria

, but

no

req

uire

men

t fo

r su

bjec

tive

mem

ory

com

plai

ntde

men

tia:

DSM

-IV

Ran

dom

sam

plin

g fr

om

list p

rovi

ded

by th

e lo

cal

regi

stry

off

ice

in L

eipz

ig

No

grou

p di

ffer

ence

s;

lang

uage

sco

re n

ot a

si

gnif

ican

t pr

edic

tor

Cac

capo

lo-V

an V

liet

et a

l. (2

003)

BD

AE

–Rep

etit

ion

of

phra

ses

NE

(n

=23

0)Q

D (

n=

155)

mild

AD

(n

=24

4)m

oder

ate

AD

(n=

480)

seve

re A

D (

n=

376)

very

sev

ere

AD

(n

=24

7)

QD

: cog

niti

ve im

pair

men

t su

ffic

ient

or

clos

e to

su

ffic

ient

for

a d

iagn

osis

of

dem

enti

a; n

o fu

ncti

onal

im

pair

men

tA

D: N

INC

DS-

AD

RD

A

crit

eria

Mem

ory

Dis

orde

rs

Cen

ter/

recr

uite

d fo

r a

stud

y of

con

trol

s

NE

=Q

D=

mild

A

D=

mod

erat

e A

D >

se

vere

AD

> v

ery

seve

re A

D

Col

lie e

t al

. (20

02)

Synt

acti

c an

d se

man

tic

reas

onin

gE

lder

ly a

dult

s (n

=17

4),

23 o

f w

hom

wer

e im

pair

ed o

n 3

cons

ecut

ive

asse

ssm

ents

CE

RA

D b

atte

ry (

Mor

ris

et a

l., 1

988b

)R

ecru

ited

fro

m a

n on

goin

g st

udy

on a

ging

at

an

inde

pend

ent

rese

arch

inst

itut

e in

M

elbo

urne

, Aus

tral

ia

Synt

acti

c re

ason

ing:

% c

orre

ct

sign

ific

ant

Sem

anti

c re

ason

ing

not

sign

ific

ant

Synt

acti

c re

ason

ing:

0.1

4

Cro

ot e

t al

. (19

99)

TR

OG

Wor

d–pi

ctur

e m

atch

ing

(Hod

ges

& P

atte

rson

, 19

95)

PP

T

NE

(n

=46

)m

inim

al A

D (

n=

16)

mild

AD

(n

=16

)m

oder

ate

AD

(n=

14)

NIN

CD

S-A

DR

DA

cri

teri

a;

min

imal

: MM

SE=

24–3

0m

ild: M

MSE

=18

–23

mod

erat

e: M

MSE

=2–

17

Mem

ory

Clin

ic a

t A

dden

broo

ke’s

H

ospi

tal,

Cam

brid

ge

TR

OG

, blo

cks

corr

ect:

NE

>

min

imal

=m

ild >

mod

erat

eT

RO

G, i

tem

s co

rrec

t: N

E >

m

ild >

mod

erat

e,

min

imal

=m

ildsy

ntac

tic

mis

inte

rpre

tati

ons

acco

unte

d fo

r m

ore

erro

rs

than

exp

ecte

d by

cha

nce

othe

r ta

sks:

p-v

alue

not

re

port

edD

e Ja

ger

& B

udge

(2

005)

syno

nym

s te

st

(War

ring

ton

et a

l., 1

998)

Bas

elin

e:N

E (

n=

117)

MC

I (n

=40

)3-

year

fol

low

up:

NE

(n

=85

)M

CI

(n=

49)

MC

I: >

1.5

SD

bel

ow c

ontr

ol

mea

n on

mem

ory

test

ing

Tal

ks/r

adio

adv

erti

sing

in

Oxf

ords

hire

for

tho

se

who

tho

ught

tha

t th

eir

heal

th, m

emor

y an

d th

inki

ng w

ere

good

co

mpa

red

to t

hat

of

thei

r pe

ers

Cla

ssif

icat

ion

at 4

yea

rs n

ot

pred

icte

d by

syn

onym

s te

st

De

Jage

r et

al.

(200

3)T

oken

Tes

tN

E (n

=51

)M

CI

(n=

29)

AD

(n

=60

)V

CI

(n=

8)V

aD (

n=

4)

MC

I: P

eter

sen

crit

eria

AD

: N

INC

DS-

AD

RD

A c

rite

ria

VC

I: H

achi

nski

cri

teri

aV

aD: N

INC

DD

S/A

IRE

N

crite

ria

(G. G

old

et a

l., 1

997)

Par

tici

pant

s wer

e re

crui

ted

from

the

Oxf

ord

Pro

ject

T

o In

vest

igat

e M

emor

y an

d A

gein

g (O

PT

IMA

) st

udy

NE

=M

CI

> A

DM

CI

vs. A

D: 0

.6V

aD a

lso

exhi

bite

d de

fici

tsN

E v

s. C

VD

(V

aD+

VC

I):

1.03


551

Dev

anan

d et

al.

(199

7)B

DA

E c

ateg

ory

nam

ing

QD

(n

=62

), 2

6 of

w

hom

wen

t on

to

deve

lop

dem

enti

a

Dem

enti

a: D

SM-I

II c

rite

ria

AD

: NIN

CD

S-A

DR

DA

cr

iter

iaQ

D: c

ogni

tive

impa

irm

ent,

fa

ll be

twee

n “n

orm

al”

and

“dem

enti

a” c

ateg

orie

s

Mem

ory

Dis

orde

rs C

linic

Non

conv

erte

rs=

conv

erte

rs

Dud

as e

t al

. (20

05)

PP

T (

pict

ures

)N

E (n

=29

)M

CI

(n=

24)

AD

(n=

22)

Pet

erse

n cr

iter

iaM

emor

y C

linic

at

Add

enbr

ooke

’s

Hos

pita

l, C

ambr

idge

NE

> M

CI=

AD

NE

vs.

MC

I: 0

.80

Dw

olat

zky

et a

l. (2

003)

Min

dstr

eam

s ba

tter

y (v

erba

l tes

ts: s

elec

ting

na

me

from

4 c

hoic

es;

sele

ctin

g rh

ymin

g w

ord

from

4 c

hoic

es)

NE

(n=

39)

MC

I (n

=29

)A

D (n

=30

)

Pet

erse

n cr

iter

iaM

emor

y cl

inic

sN

E >

MC

I >

mild

AD

on

both

mea

sure

sN

amin

g: N

E v

s. M

CI,

0.7

9;

MC

I vs

. AD

, 0.9

8R

hym

ing:

NE

vs.

MC

I, 1

.20;

M

CI

vs. A

D, 0

.54

Flic

ker

et a

l. (1

991)

voca

bula

ry, c

ateg

ory

retr

ieva

l, ob

ject

fu

ncti

on r

ecal

l, ob

ject

na

me

reco

gnit

ion,

ob

ject

fun

ctio

n re

cogn

itio

n, o

bjec

t id

enti

fica

tion

NE

(n=

32)

Mild

ly im

pair

ed (n

=32

)G

DS

rati

ng o

f 3

Sele

cted

fro

m p

arti

cipa

nts

in a

ging

stu

dies

at

the

Agi

ng a

nd D

emen

tia

Res

earc

h C

ente

r, N

YU

M

edic

al C

ente

r

NE

> m

ildly

impa

ired

on

voca

bula

ry, c

ateg

ory

retr

ieva

l, ob

ject

fun

ctio

n re

call,

obj

ect

nam

e re

cogn

itio

n

Voc

abul

ary:

0.8

Cat

egor

y re

trie

val:

1.2

Obj

ect

func

tion

: 0.5

4O

bjec

t nam

e re

cogn

itio

n: 0

.74

Gri

ffit

h et

al.

(200

6)T

oken

Tes

t (s

hort

for

m)

NE

(n=

49)

MC

I (n

=49

)P

eter

sen

crit

eria

Mem

ory

Dis

orde

rs C

linic

or

rec

ruit

ed f

rom

co

mm

unit

y

NE

> M

CI

NE

vs.

MC

I: 0

.52

conv

erte

rs=

nonc

onve

rter

s

Gua

rch

et a

l. (2

004)

WA

IS V

ocab

ular

yN

E (n

=34

)SM

L (n

=43

), 1

0 of

w

hom

wen

t on

to

deve

lop

AD

Subj

ecti

ve m

emor

y lo

ss;

neur

opsy

chol

ogic

al

test

s no

t us

ed a

s in

clus

ion/

excl

usio

n cr

iter

ia.

Clin

ical

psy

chol

ogy

serv

ice

at t

he H

ospi

tal C

linic

i P

rovi

ncia

l, B

arce

lona

.

Non

conv

erte

rs=

conv

erte

rs

Hod

ges

& P

atte

rson

(1

995)

Nam

ing

to v

erba

l de

scri

ptio

n, a

nsw

erin

g of

sem

anti

c fe

atur

e qu

esti

ons,

w

ord–

pict

ure

mat

chin

g, P

PT

NE

(n=

24)

min

imal

AD

(n=

17)

mild

AD

(n=

52)

mod

erat

e A

D (n

=18

)

NIN

CD

S-A

DR

DA

cri

teri

aM

emor

y C

linic

at

Add

enbr

ooke

’s

Hos

pita

l, C

ambr

idge

Nam

ing

to d

escr

ipti

on: N

E >

m

inim

al=

mild

> m

oder

ate

Sem

anti

c fe

atur

e qu

esti

ons:

N

E >

min

imal

=m

ild >

m

oder

ate

Wor

d-pi

ctur

e m

atch

ing:

N

E=

min

imal

=m

ild >

m

oder

ate

PP

T: N

E >

min

imal

=m

ild >

m

oder

ate

(Con

tinu

ed)


552

AP

PE

ND

IX C

(C

ontin

ued)

Aut

hors

Tes

t us

edG

roup

s+sa

mpl

e si

zes

Dia

gnos

tic

crit

eria

Rec

ruit

men

t pr

oced

ure

Sig

nifi

cant

eff

ects

Eff

ect

size

s

Hod

ges

et a

l. (1

996)

Gen

erat

ion

of v

erba

l de

fini

tion

s in

res

pons

e to

spo

ken

nam

e (n

=12

)

NE

(n=

10)

min

imal

AD

(n=

16)

mild

AD

(n=

17)

mod

erat

e A

D (n

=18

)

AD

: NIN

CD

S-A

DR

DA

cr

iter

iam

inim

al: M

MSE

=24

–30

mild

: MM

SE=

18–2

3m

oder

ate:

MM

SE=

2–17

Mem

ory

Clin

ic a

t A

dden

broo

ke’s

H

ospi

tal,

Cam

brid

ge

NE

> m

inim

al >

mild

>

mod

erat

eC

ore

conc

ept

info

rmat

ion:

NE

vs.

min

imal

AD

, 1.1

4;

min

imal

AD

vs.

mild

AD

, 0.

76; m

ild A

D v

s. m

oder

ate

AD

, 1.3

3P

rodu

ctio

n of

sup

eror

dina

te

cate

gory

:N

E v

s. m

inim

al A

D, 1

.14;

m

inim

al A

D v

s. m

ild A

D,

0.98

; mild

AD

vs.

mod

erat

e A

D, 0

.62

AD

s: d

efin

itio

ns h

ad le

ss

corr

ect

info

rmat

ion,

so

met

imes

fai

led

to c

onve

y co

re c

once

pt; e

spec

ially

true

in

min

imal

and

mild

gro

ups

of it

ems

they

fai

led

to n

ame

Jaco

bs e

t al

. (19

95)

16 it

ems

from

B

DA

E–C

ompl

ex

Idea

tion

al M

ater

ial

BD

AE

–Rep

etit

ion

of

Phr

ases

(hi

gh

freq

uenc

y on

ly)

nond

emen

ted

elde

rly

(n=

443)

, 41

of w

hom

ha

d de

velo

ped

AD

at

2 ye

ar f

ollo

w-u

p

NIN

CD

S-A

DR

DA

cri

teri

aN

orth

Man

hatt

an A

ging

P

roje

ct, a

com

mun

ity-

base

d, e

pide

mio

logi

c st

udy

of d

emen

tia

in

nort

hern

Man

hatt

an,

NY

No

sign

ific

ant

addi

tion

al

prog

nost

ic v

alue

from

the

se

test

s

Jorm

et

al. (

2005

)L

angu

age

subs

ecti

on o

f C

ASI

(T

eng

et a

l.,

1994

), c

ompr

isin

g re

adin

g, w

riti

ng &

fo

llow

ing

a si

mpl

e co

mm

and

Japa

nese

-Am

eric

an

men

age

d 71

–93

(n=

1611

), 5

2 of

w

hom

wen

t on

to

deve

lop

dem

enti

a

DSM

-III

-RR

ecru

ited

fro

m p

opul

atio

nP

redi

cted

inci

dent

dem

enti

a up

to

3 ye

ars

befo

re o

nset

bu

t no

t 3–

6 ye

ars

befo

re

onse

t

0.24

Lam

bon

Ral

ph e

t al.

(200

3)W

ord–

pict

ure

mat

chin

g;

nam

ing

to v

erba

l de

scri

ptio

n; s

eman

tic

feat

ure

ques

tion

s;

Tok

en T

est;

TR

OG

; re

adin

g of

reg

ular

and

ex

cept

ion

wor

ds;

NA

RT

NE

(n=

48)

MC

I (n

=17

)m

ild A

D (n

=22

) m

oder

ate

AD

(n=

8)se

vere

AD

(n=

8)

Subj

ecti

ve m

emor

y im

pair

men

t, c

orro

bora

ted

by a

spo

use/

fam

ily

mem

ber;

pre

serv

atio

n of

A

DL

; im

pair

men

t on

at

leas

t on

e te

st o

f m

emor

y;

norm

al p

erfo

rman

ce o

n te

sts

of la

ngua

ge,

visu

ospa

tial

and

exe

cuti

ve

func

tion

; MM

SE >

24

Mem

ory

Clin

ic a

t A

dden

broo

ke’s

H

ospi

tal,

Cam

brid

ge

Tok

en T

est:

NE

> M

CI

All

othe

r te

sts:

NE

=M

CI


553

Lóp

ez e

t al

. (20

06)

AM

NA

RT

NE

(n=

374)

MC

I-A

(n=

10)

MC

I-M

D (n

=28

)

MC

I-A

: >1.

5 S

Ds

belo

w

cont

rols

in d

elay

ed

reca

ll+

decl

ine

in c

ogni

tive

fu

ncti

onin

g; M

CI-

MD

; >

1.5

SD

s in

at

leas

t on

e co

gnit

ive

dom

ain

othe

r th

an m

emor

y/on

e ab

norm

al t

est

in ≥

2 do

mai

ns.

5,20

1 no

nins

titu

tion

aliz

ed

indi

vidu

als

over

65;

re

crui

ted

from

fou

r co

mm

unit

ies

usin

g P

art

A M

edic

are

list

in

1988

–198

9; 6

87 A

fric

an-

Am

eric

ans

recr

uite

d in

sa

me

man

ner

in

1992

–199

3

NE

=M

CI-

A >

MC

I-M

DN

E v

s. M

CI-

MD

: 0.9

5M

CI-

MD

vs.

MC

I-A

: 1.8

0

Mar

cos

et a

l. (2

006)

CA

MC

OG

Lan

guag

e su

btes

tP

MC

I (n

=38

)M

CI:

Pet

erse

n cr

iter

iaR

efer

red

by n

euro

logi

sts

or g

eria

tric

spe

cial

ists

Voc

abul

ary:

PM

CI=

SMC

IL

angu

age:

1.0

9

WA

IS V

ocab

ular

ySM

CI

(n=

44)

AD

: NIN

CD

S-A

DR

DA

cr

iter

iaL

angu

age:

PM

CI

< S

MC

I Se

nsit

ivit

y=

79%

. Sp

ecif

icit

y=

61%

Mas

ur e

t al

. (19

94)

WA

IS V

ocab

ular

y (W

echs

ler,

195

5)N

onde

men

ted

elde

rly

(n=

317)

, 64

of w

hom

de

velo

ped

AD

in a

fo

llow

-up

of a

t lea

st 4

ye

ars

DSM

-III

, N

INC

DS-

AD

RD

A c

rite

ria

Rec

ruit

ed f

rom

co

mm

unit

yN

ot a

sig

nifi

cant

pre

dict

or

Meg

uro

et a

l. (2

004)

Lan

guag

e su

bsec

tion

of

CA

SI (

Ten

g et

al.,

19

94),

com

pris

ing

read

ing,

wri

ting

&

follo

win

g a

sim

ple

com

man

d

NE

(n=

968)

CD

R 0

.5, A

D (n

=95

)C

DR

O.5

, UD

(n=

94)

CD

R 0

.5, I

D (n

=22

7)C

DR

0.5

, oth

ers

(n=

37)

CD

R 1

and

2 (n

=80

)

UD

: onl

y m

emor

y is

impa

ired

ID: i

mpa

irm

ent

in m

emor

y an

d ≤2

oth

er c

ogni

tive

do

mai

nsO

ther

s: im

pair

men

t in

m

emor

y an

d ≥3

oth

er

cogn

itiv

e do

mai

nsD

emen

tia:

DSM

-III

-R

All

olde

r re

side

nts

in T

ajir

i w

ere

targ

eted

CD

R 0

< C

DR

0.5

<

CD

R <

1 a

nd 2

CD

R 0

.5 (

AD

vs.

UD

): 0

.72

CD

R 0

.5 (

DA

T)

< U

D a

nd I

DC

DR

0.5

(A

D v

s. I

D):

0.37

Mey

er e

t al

. (20

02)

MM

SEM

CI

(n=

73),

35

of

who

m d

evel

oped

A

D a

nd 1

5 of

who

m

deve

lope

d V

aD

duri

ng a

n av

erag

e of

3.

88 y

ears

of f

ollo

w-u

p

MM

SE >

1 S

D b

elow

mea

n fo

r ag

e &

edu

cati

on;

mem

ory

com

plai

nts;

no

dem

enti

a

Vol

unte

ers

enro

lled

in

long

itud

inal

stu

dies

of

agin

g an

d de

men

tia

thro

ugh

Bay

lor

Col

lege

of

Med

icin

e

No

grou

p ef

fect

s

Nes

tor

et a

l. (2

003)

PP

T (

pict

ure

vers

ion)

NE

(n=

15)

MC

I (n

=10

)A

D (n

=10

)

MC

I: in

sidi

ous

onse

t mem

ory

sym

ptom

s, o

bjec

tive

m

emor

y im

pair

men

t, n

o ot

her

sign

ific

ant

defi

cits

AD

: NIN

CD

S-A

DR

DA

cr

iter

ia

Mem

ory

clin

icM

CI

> A

D

(Con

tinu

ed)


554

AP

PE

ND

IX C

(C

ontin

ued)

Aut

hors

Tes

t us

edG

roup

s+sa

mpl

e si

zes

Dia

gnos

tic

crit

eria

Rec

ruit

men

t pr

oced

ure

Sig

nifi

cant

eff

ects

Eff

ect

size

s

Nor

dlun

d et

al.

(200

5)T

oken

Tes

tA

SLD

rep

etit

ion

(Cro

sson

, 199

6)

Tok

en T

est:

NE

(n=

35)

MC

I (n

=11

0)A

SLD

rep

etiti

on:

NE

(n=

31)

MC

I (n

=86

)

Subj

ecti

ve a

nd o

bjec

tive

m

emor

y im

pair

men

t >

6

mon

ths;

pos

itiv

e ou

tcom

e on

ste

pwis

e co

mpa

rati

ve

stat

us a

naly

sis

(ST

EP

, W

allin

et

al.,

1996

), I

-Fle

x (R

oyal

l et

al.,

1992

),

MM

SE o

r C

DR

; MM

SE

≥25;

not

mor

e th

an 2

+ve

ou

tcom

es o

n ST

EP

Mem

ory

clin

icN

E >

MC

I in

bot

h te

sts

Tok

en T

est:

0.7

3

ASL

D: 0

.75

Pyo

et

al. (

2006

)A

DA

S-C

og L

angu

age,

C

ompr

ehen

sion

and

W

ord-

Fin

ding

D

iffi

cult

y ta

sks

NE

(n=

843)

unce

rtai

n/M

CI

(n=

135)

AD

, CD

R=

0.5

(n=

30)

AD

, CD

R=

1 (n

=12

5)

MC

I: C

DR

=0.

5, m

emor

y lo

ss b

ut n

o de

men

tia

Med

ia a

ppea

lsL

angu

age:

NE

< M

CI=

AD

(CD

R 0

.5) <

A

D (

CD

R 1

)C

ompr

ehen

sion

:N

E <

MC

I <

AD

(C

DR

0.

5)=

AD

(C

DR

1)

Wor

d-fi

ndin

g di

ffic

ulty

:N

E <

MC

I <

AD

(C

DR

1)

<

AD

(C

DR

0.5

)

Lan

guag

e:N

E v

s. M

CI,

0.7

3A

D (

0.5)

vs.

AD

(1)

, 0.0

8C

ompr

ehen

sion

: NE

vs.

M

CI,

0.5

3M

CI

vs. A

D 0

.5, 0

.53

Wor

d fi

ndin

g di

ffic

ulty

:N

E v

s. M

CI,

0.4

7M

CI

vs. A

D (

1), 0

.24

AD

(1)

vs.

AD

(0.

5), 0

.12

Rib

eiro

et

al. (

2006

)M

odif

ied

vers

ion

of

Tok

en T

est

from

B

atte

ry o

f L

isbo

n fo

r th

e A

sses

smen

t of

Dem

enti

a

NE

(n=

63)

MC

I (n

=11

6)Su

bjec

tive

mem

ory

com

plai

nts;

≥1.

5 S

D

belo

w n

orm

al o

n de

laye

d re

call;

pre

serv

ed A

DL

; m

aint

aine

d pr

ofes

sion

al,

soci

al a

nd f

amili

al

acti

viti

es, s

core

<3

on t

he

firs

t pa

rt o

f th

e B

less

ed

Dem

enti

a Sc

ale;

pre

serv

ed

gene

ral c

ogni

tive

fun

ctio

n.

Dem

enti

a O

utpa

tien

t C

linic

, Hos

pita

l San

ta

Mar

ia, a

nd a

Mem

ory

Clin

ic, L

isbo

n

33.7

% o

f MC

I pa

tien

ts h

ad a

n im

pair

men

t in

the

Tok

en

Tes

t (<

1.5

SD

bel

ow m

ean

for

age

& e

duca

tion

)

Ric

hard

s et

al.

(199

9)E

co w

ord

com

preh

ensi

on

subt

est

(RT

mea

sure

s)11

1 in

divi

dual

s,

clas

sifi

ed a

s N

E

(n=

74),

AA

MI

(n=

37),

or

AA

CD

(n

=39

).

AA

MI:

mem

ory

impa

irm

ent,

no

dem

enti

aA

AC

D: i

mpa

irm

ent

in o

ne

dom

ain:

mem

ory/

lear

ning

, at

tent

ion/

con

cent

rati

on,

visu

ospa

tial

rea

soni

ng,

lang

uage

, vis

uosp

atia

l fu

ncti

on

Ran

dom

ly r

ecru

ited

fro

m

600

gene

ral m

edic

al

prac

tice

s in

sou

ther

n F

ranc

e

NE

> A

AC

D

NE

> A

AM

IA

AM

I: 0

.57

AA

CD

: 1.0

4


555

Sacu

iu e

t al

. (20

05)

Syno

nym

tes

t (i

dent

ify

syno

nym

am

ongs

t 5

alte

rnat

ives

)

nond

emen

ted

elde

rly

(n=

313)

, 58

of w

hom

w

ent

on t

o de

velo

p A

D in

3 y

ears

Dem

enti

a: D

SM-I

I-R

AD

: NIN

CD

S-A

DR

DA

cr

iter

ia

All

indi

vidu

als

born

in

1901

–190

2 in

G

othe

nbur

g,

Swed

en w

ere

invi

ted

to p

arti

cipa

te

Pre

dict

ed a

ll de

men

tia

and

VaD

, but

not

AD

; Se

nsit

ivit

y=

68%

, sp

ecif

icit

y=

48%

, P

PV

=22

.7, N

PV

=87

.0 f

or

all d

emen

tia

Saxt

on e

t al

. (20

04)

WA

IS–R

Voc

abul

ary

nond

emen

ted

elde

rly

(n=

693)

, 72

of w

hom

de

velo

ped

AD

wit

hin

1.5–

8 ye

ars

(1.5

–3.4

ye

ars:

n=

24; 3

.5–5

.0

year

s: n

=20

; 5.1

–8.1

ye

ars:

n=

28)

NIN

CD

S-A

DR

DA

cri

teri

aSe

lect

ed f

rom

par

tici

pant

s re

crui

ted

from

the

com

-m

unit

y as

par

t of

the

C

ardi

ovas

cula

r H

ealt

h St

udy

Non

conv

erte

rs=

conv

erte

rs

Smal

l et

al. (

2000

)R

eadi

ng &

wri

ting

su

bsec

tion

s of

Sw

edis

h M

MSE

nond

emen

ted

elde

rly

(n=

569)

, 73

of w

hom

w

ent o

n to

dev

elop

A

D

DSM

-III

-RSu

bjec

ts p

arti

cipa

ting

in

Kun

gsho

lmen

pro

ject

w

ho w

ere

not

dem

ente

d at

fir

st f

ollo

w-u

p (s

ee

Smal

l et

al.,

1997

)

Non

conv

erte

rs=

conv

erte

rs

Tab

ert

et a

l. (2

006)

BD

AE

rep

etit

ion

&

com

preh

ensi

onN

E (n

=83

)M

CI

(n=

148)

Age

≥40

, cog

niti

ve im

pair

-m

ent

for

6 m

onth

s–10

ye

ars,

CD

R 0

–0.5

. For

m

emor

y: M

MSE

, SR

T,

WA

IS–R

per

form

ance

IQ

. If

no

form

al c

ogni

tive

de

fici

t: s

ubje

ctiv

e m

emor

y de

clin

e, p

osit

ive

scor

e on

1

or m

ore

of t

he f

irst

8 it

ems

of t

he m

odif

ied

Ble

ssed

F

unct

iona

l Act

ivit

y Sc

ale.

Mem

ory

diso

rder

s cl

inic

; N

E r

ecru

ited

by

adve

rtis

emen

t

NE

> M

CI

on b

oth

mea

sure

sN

onco

nver

ters

= c

onve

rter

s on

bot

h m

easu

res

Rep

etit

ion:

0.2

7 C

ompr

ehen

sion

: 0.2

0

Tho

mps

on e

t al

. (2

002)

NA

RT

NE

(n=

31)

qAD

(n=

28)

AD

(n=

31)

AD

: NIN

CD

S-A

DR

DA

cr

iter

iaqA

D: c

ompl

aint

s of

epi

sodi

c m

emor

y im

pair

men

t but

no

dem

enti

a

Mem

ory

Clin

ic a

t A

dden

broo

ke’s

H

ospi

tal,

Cam

brid

ge

NE

=qA

D=

AD

Tia

n et

al.

(200

3)F

AST

(E

nder

by e

t al

., 19

87)

QD

( n=

195)

, 135

see

n fo

r fo

llow

up a

t 24.

5 m

onth

s; 3

7 co

nver

ted

to d

emen

tia

Obj

ecti

ve e

vide

nce

of

cogn

itiv

e im

pair

men

t bu

t no

dem

enti

a

Bri

stol

Mem

ory

Dis

orde

rs

Clin

icN

onco

nver

ters

=co

nver

ters

(Con

tinu

ed)


556

AP

PE

ND

IX C

(C

ontin

ued)

Aut

hors

Tes

t us

edG

roup

s+sa

mpl

e si

zes

Dia

gnos

tic

crit

eria

Rec

ruit

men

t pr

oced

ure

Sig

nifi

cant

eff

ects

Eff

ect

size

s

Tou

chon

& R

itch

ie

(199

9)M

ean

RT

on

wor

d an

d sy

ntax

com

preh

ensi

on;

read

ing

(fro

m E

CO

)

NE

(n=

150)

nond

emen

ted

elde

rly

(n=

359)

, 22

of w

hom

de

velo

ped

AD

in 3

rd

year

Dem

enti

a: D

SM-I

II-R

cr

iter

iaA

D: N

INC

DS-

AD

RD

A

crit

eria

Gen

eral

pra

ctit

ione

r re

crui

tmen

t ne

twor

kB

oth

wor

d an

d sy

ntax

co

mpr

ehen

sion

pre

dict

ed

inci

dent

dem

enti

a 2

year

s pr

ior;

inte

ract

ion

wit

h ed

ucat

ion

Rea

ding

pre

dict

ed d

emen

tia;

no

inte

ract

ion

wit

h ed

ucat

ion

Wor

d co

mpr

ehen

sion

: 1.5

7Sy

ntax

com

preh

ensi

on: 0

.97

Rea

ding

: 1.9

Van

denb

ulck

e et

al.

(200

7)A

AT

(G

raet

s et

al.,

19

92);

Ver

bal

asso

ciat

ion

test

of

the

psyc

holin

guis

tic

asse

ssm

ent

of

lang

uage

pro

cess

ing

in a

phas

ia;

spon

tane

ous

spee

ch

NE

(n

=13

)M

CI

(n=

13)

CD

R=

0.5,

mem

ory

decl

ine,

ot

her

cogn

itiv

e do

mai

ns

and

acti

viti

es o

f dai

ly li

ving

re

lati

vely

pre

serv

ed

Mem

ory

Clin

ic, U

nive

rsit

y H

ospi

tal G

asth

uisb

erg,

L

euve

n

1/13

impa

ired

(>

2 S

D b

elow

N

E m

ean)

in A

AT

(na

min

g su

btes

t), s

eman

tic

stru

ctur

e in

spo

ntan

eous

spe

ech

1/13

impa

ired

in A

AT

(au

di-

tory

wor

d-pi

ctur

e m

atch

ing

subt

est)

and

sem

anti

c st

ruc-

ture

in s

pont

aneo

us s

peec

h1/

13 im

pair

ed in

AA

T (

visu

al

wor

d-pi

ctur

e m

atch

ing

subt

est)

1/13

impa

ired

in s

ynta

ctic

st

ruct

ure

in s

pont

aneo

us

spee

chW

ang

et a

l. (2

006)

Lan

guag

e su

bsec

tion

of

CA

SI (

Ten

g et

al.,

19

94),

com

pris

ing

read

ing,

wri

ting

&

follo

win

g a

sim

ple

com

man

d

NE

(n=

20)

MC

I (n

=58

)A

D (n

=20

)

MC

I: P

eter

sen

crit

eria

AD

: NIN

CD

S-A

DR

DA

cr

iter

ia

Neu

rolo

gica

l clin

ics

NE

> A

DM

CI

> A

Dco

nver

ters

> n

onco

nver

ters

MC

I vs

. AD

: 0.4

8N

onco

nver

ters

vs.

con

vert

ers:

0.

54

Not

e. E

ffec

t si

zes

are

repo

rted

whe

re p

ossi

ble.

AA

CD

= a

ge-a

ssoc

iate

d co

gnit

ive

decl

ine.

AA

CD

-M =

age

-ass

ocia

ted

cogn

itiv

e de

clin

e-m

odif

ied.

AA

T=

Aac

hen

Aph

asie

Tes

t. A

D=

Alz

heim

er’s

dis

-ea

se.

AD

AS-

Cog

=A

lzhe

imer

Dis

ease

Ass

essm

ent

Scal

e–C

ogni

tive

sub

scal

e. A

MN

AR

T=

Am

eric

an v

ersi

on o

f N

atio

nal

Rea

ding

Tes

t. A

SLD

=A

sses

smen

t of

Sub

tle

Lan

guag

e D

isor

ders

.B

DA

E=

Bos

ton

Dia

gnos

tic

Aph

asia

Exa

min

atio

n. C

AM

CO

G =

Cam

brid

ge C

ogni

tive

Exa

min

atio

n. C

ASI

=C

ogni

tive

Abi

litie

s Sc

reen

ing

Inst

rum

ent.

CE

RA

D=

Con

sort

ium

to

Est

ablis

h a

Reg

istr

yfo

r A

lzhe

imer

’s D

isea

se. E

RV

T=

Ext

ende

d R

ange

Voc

abul

ary

Tes

t. F

AST

=F

renc

hay

Aph

asia

Scr

eeni

ng T

est.

IC

D-1

0 =

Int

erna

tion

al S

tati

stic

al C

lass

ific

atio

n of

Dis

ease

s an

d R

elat

ed H

ealt

h P

rob-

lem

s–10

th R

evis

ion.

MC

I=m

ild c

ogni

tive

impa

irm

ent.

MM

SE=

Min

i Men

tal S

tate

Exa

min

atio

n. N

AR

T=

Nat

iona

l Adu

lt R

eadi

ng T

est.

NE

=no

rmal

eld

erly

. NIN

CD

S-A

DR

DA

=N

atio

nal I

nsti

tute

of N

euro

logi

cal a

nd C

omm

unic

ativ

e D

isor

ders

. NP

V=

nega

tive

pre

dict

ive

valu

e. P

MC

I=pr

ogre

ssiv

e M

CI.

PP

T=

Pyr

amid

s an

d P

alm

s te

st. P

PV

=po

siti

ve p

redi

ctiv

e va

lue.

qA

D=

ques

tion

able

AD

.Q

D=

ques

tion

able

dem

enti

a. R

T=

reac

tion

tim

e. S

MC

I=st

able

MC

I. S

ML

=su

bjec

tive

mem

ory

loss

. SR

T =

Bus

cke

Sele

ctiv

e R

emin

ding

Tes

t. T

RO

G=

Tes

t fo

r th

e R

ecep

tion

of

Gra

mm

ar.

VaD

=va

scul

ar d

emen

tia.

VC

I=va

scul

ar c

ogni

tive

impa

irm

ent.

WA

IS=

Wec

hsle

r A

dult

Int

ellig

ence

Sca

le.


NCEN Language performance in Al zheimer’s disease and mild ...

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Transcript of NCEN Language performance in Al zheimer’s disease and mild ...