Clinical Manifestations and Diagnosis of Alzheimer Disease

Official reprint from UpToDate®

www.uptodate.com

©2012 UpToDate®

Author

Thomas J Grabowski, Jr, MD

Section Editor

Steven T DeKosky, MD, FAAN

Deputy Editor

Janet L Wilterdink, MD

Clinical manifestations and diagnosis of Alzheimer disease

Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Jun 2012. | This topic last updated: Mar 9, 2012.

INTRODUCTION — Alzheimer disease (AD) is a neurodegenerative disorder of uncertain cause and

pathogenesis that primarily affects older adults. The main clinical manifestations of AD are selective memory

impairment and dementia. AD is the most common cause of dementia. While treatments are available that can

modulate the course of the disease and/or ameliorate some symptoms, there is no cure, and the disease

inevitably progresses in all patients.

This topic reviews the clinical manifestations and diagnosis of AD. Other topics review the risk factors and

treatment of AD and the clinical manifestations of other causes of dementia and cognitive impairment. (See "Risk

factors for dementia" and "Treatment of dementia" and "Cholinesterase inhibitors in the treatment of

dementia" and "Mild cognitive impairment: Epidemiology, pathology, and clinical assessment" and "Clinical

features and diagnosis of dementia with Lewy bodies" and "Frontotemporal dementia: Clinical features and

diagnosis" and "Etiology, clinical manifestations, and diagnosis of vascular dementia".)

DEMOGRAPHIC FEATURES — Alzheimer disease (AD) is characteristically a disease of older age [1]. It is

exceptional for AD to occur before age 60. The incidence and prevalence of AD increase exponentially with age.

(See "Risk factors for dementia", section on 'Age'.)

AD is slightly more common in women than men, with a relative risk of 1.5 [2]. This does not appear to be

explained by the greater longevity in women.

There are inherited forms of AD, all autosomal dominant, that routinely present before age 65, and frequently in

the fifth decade or earlier. These account for less than 5 percent of all cases of AD. Patients with Down

syndrome develop AD at an earlier age, 10 to 20 years younger than the general population with AD [3]. (See

"Risk factors for dementia", section on 'Genetic factors'.)

Other risk categories for AD are discussed separately. (See "Risk factors for dementia".)

CLINICAL FEATURES

Memory impairment — Memory impairment is an essential feature of AD and is often its earliest manifestation.

Even when not the primary complaint, memory deficits can be elicited in most patients with AD at the time of

presentation.

The pattern of memory impairment in AD is also distinctive. Declarative memory for facts and events, which

depend on mesial temporal and neocortical structures are profoundly affected in AD, while subcortical systems

supporting procedural memory and motor learning are relatively spared until quite late in the disease. A subset of

declarative memory, that of specific events and contexts (episodic memory) is more profoundly impaired in early

AD, compared with memory for facts such as vocabulary and concepts (semantic memory), which often

becomes impaired somewhat later. Semantic memory is encoded in neocortical (nonmesial) temporal regions.

Within episodic memory, there is a distinction between immediate recall (eg, mental rehearsal of a phone

number), memory for recent events (which comes into play once material that has departed from consciousness

must be recalled), and memory of more distant events. Memory for recent events, served by the hippocampus,

entorhinal cortex, and related structures in the mesial temporal lobe, is prominently impaired in early AD [4-6]. In

Clinical manifestations and diagnosis of Alzheimer disease http://www.uptodate.com/contents/clinical-manifestations-and-diagnos...

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contrast, immediate memory (encoded in the sensory association and prefrontal cortices) is spared early on, as

are memories that are consolidated for long periods of time (years), which can be recalled without hippocampal

function.

The early memory deficit in AD is most precisely described as anterograde long-term episodic amnesia. Because

the absolute time interval over which long-term memory can fail can actually be short (eg, inability to recall a few

words after a couple minutes of distraction), patients and caregivers typically refer to "short-term memory"

problems. For this reason, we try to avoid the confusion afforded by the technical terms of long-term and

short-term memory and use the term "recent memory impairment" to refer to the characteristic impairment.

Memory deficits develop insidiously and progress slowly over time, evolving to include deficits of semantic

memory and immediate recall. Impairments of procedural memory appear only in late stages of AD.

Memory is usually tested by asking patients to recall three objects immediately and then at a delay of 5 to 10

minutes. Questions about orientation and recent current events are also useful memory tests. (See "The detailed

neurologic examination in adults", section on 'Memory'.) Clinicians should not rely on a patient's report of

memory impairment, as many older individuals are unreliable reporters of their own memory impairment and can

both over and under estimate their deficits [7].

Amnestic mild cognitive impairment — A state of circumscribed anterograde long-term memory

impairment, with preserved general cognitive, social functioning is known as amnestic mild cognitive impairment

(MCI) [8]. Amnestic MCI is increasingly recognized as an early stage of AD, with a conversion rate to dementia

at about 10 to 15 percent per year [8,9]. (See "Mild cognitive impairment: Epidemiology, pathology, and clinical

assessment", section on 'Amnestic MCI' and "Mild cognitive impairment: Prognosis and treatment", section on

'Progression to dementia'.)

Formal clinical diagnostic criteria for MCI due to AD have recently been developed by a panel convened by the

National Institute on Aging and The Alzheimer Association [10]. These include:

A concern regarding cognition reported by the patient or informant or observed by clinician

Objective evidence of impairment in one or more cognitive domains that is not explained by age or

education

Preservation of independence in functional abilities

Not demented

Other aspects of cognitive decline — Deficits in other cognitive domains may appear with or after the

development of memory impairment. Language function and visuospatial skills tend to be affected relatively

early, while deficits in executive function and behavioral symptoms often manifest later in the disease course.

These deficits appear and progress insidiously.

Language — Verbal disfluency and anomia are often early features of AD and are sometimes the presenting

feature [11]. The first manifestations of language dysfunction usually include word-finding difficulties,

circumlocution, and reduced vocabulary in spontaneous speech and anomia on confrontational naming tests.

This progresses to include agrammatism, paraphasic errors, impoverished speech content, and impaired

comprehension. Patients can usually repeat phrases verbatim until the disease is quite advanced. (See

"Approach to the patient with aphasia", section on 'Clinical assessment'.)

Language dysfunction and loss of semantic memory are interrelated in AD. Some investigators have found that

loss of semantic fluency is an early finding in AD. When asked to generate word lists in one minute's time,

patients with AD perform significantly worse on a category fluency test (eg, lists of animals) than on a letter

fluency test (eg, lists of words beginning with F) [12-14]. Normal performance is age related, with at least 15

items expected at age 65 [13].

Visuospatial skills — Loss of visuospatial skills is an early feature of AD that is sometimes very prominent

at presentation [15-17]. Visuospatial impairments manifest as misplacement of items and difficulty navigating in

first unfamiliar then familiar terrain. Visual agnosia (inability to recognize objects) and prosopagnosia (inability to

recognize faces) are later features. Some clinicians have noted hemispatial visual neglect in their patients with

AD [18,19].


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Visuospatial skills may be tested by asking patients to copy elementary figures (eg, intersecting pentagons) and

to draw a clock face. The latter, when combined with a request to fill in the time at "ten after eleven," is a

deceptively difficult test and evaluates semantic knowledge as well as executive and spatial functioning [20].

Insight — Reduced insight into his or her deficits (anosognosia) is a characteristic feature of AD and has

been linked to frontal lobe pathology [21,22]. It is common for patients to underestimate their deficits and offer

alibis or explanations for them when they are pointed out. Interviewing a collateral historian, usually a family

member, who has known the patient over time, is helpful, and often it is the family member, not the patient, who

brings the complaint of cognitive impairment to medical attention.

Loss of insight increases over time along with overall disease severity [23]. Relative loss of insight is associated

with behavioral disturbances; those with relatively preserved insight are more likely to be depressed, while those

with more impaired insight are likely to be agitated, disinhibited, and exhibit psychotic features [24,25].

Apraxia — Dyspraxia, or difficulty performing learned motor tasks, usually occurs later in the disease after

deficits in memory and language are apparent [26]. Before it is clinically apparent, dyspraxia can be elicited by

asking the patient to perform ideomotor tasks, ie, pantomime the use of tools (eg, "show me how you would use

a comb") [27,28]. Clinical dyspraxia leads to progressive difficulty first with complex, multi-step motor activities,

then with dressing, feeding, and other self-care tasks and is a big contributor to dependency in mid to late stages

of AD [29].

Executive function — In early stages of AD, impairment in executive function may be subtle rather than

frank [30]; family members and coworkers may find them less motivated and engaged. In addition to poor insight,

reduced ability for abstract reasoning may be elicited. As the disease progresses, a more manifest alteration of

personality, poor judgment and planning, and an inability to complete tasks typically emerges.

Neuropsychiatric symptoms — Neuropsychiatric symptoms are common in AD, particularly in the middle

and late course of disease. These can begin with subtle personality changes including apathy, social

disengagement, and disinhibition. The former may be a manifestation of superimposed depression, which can be

difficult to diagnose in the setting of dementia.

More problematic in patient management is the emergence of behavioral disturbances, including agitation,

aggression, wandering, and psychosis (hallucinations, delusions, misidentification syndromes). A concomitant

medical illness, medication toxicity, and other causes of delirium should be considered whenever new behavioral

disturbances arise. The behavioral disturbances associated with AD are discussed in detail separately. (See

"Treatment of behavioral symptoms related to dementia".)

Other neurologic deficits — In the early stages, patients with AD generally have a normal neurologic

examination except for the cognitive examination. While pyramidal and extrapyramidal motor signs, myoclonus,

and seizures do occur in patients with AD, these are typically late-stage findings [31]. If these are clinically

apparent in early to middle stages, an alternative diagnosis should be considered [32]. Similarly, frontal release

signs (grasp, snout reflexes, gegenhalten) and incontinence are late, rather than early, features of AD.

Epilepsy in the setting of AD is discussed separately. (See "Seizures and epilepsy in the elderly patient: Etiology,

clinical presentation, and diagnosis", section on 'Dementia'.)

Atypical presentations — A minority of Alzheimer cases do not present in the classic fashion with progressive

amnestic dementia [33,34]. Distinguishing these cases from other causes of dementia can be challenging.

Neuropathologic studies in such patients have found Alzheimer pathology with an atypical neuroanatomic

distribution that corresponds with the anatomy of the most prominent clinical deficits; neuroimaging studies often

have corresponding findings [34-37]. Some case series suggest that these atypical presentations are more

common in early-onset (AD), patients who present before age 60 years [38,39].

Posterior cortical atrophy — This syndrome manifests with progressive cortical visual impairment

[15,33,37,40-43]. Patients are often first evaluated by optometrists or ophthalmologists for visual complaints,

such as difficulty reading and driving [34,42]. Detailed neurologic evaluation may elicit elements of the Balint

syndrome: simultanagnosia (the inability to integrate a visual scene despite adequate acuity to resolve individual

elements); optic ataxia (the inability to reach accurately under visual guidance); and ocular apraxia (the inability

to direct gaze accurately to a new target, frequently leading to difficulty reading). Other features include visual


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agnosia; ideomotor, constructional, and dressing apraxia; prosopagnosia; and visual field neglect. Less common

are visual hallucinations and frank visual field defects. This constellation of findings implicates the dorsal visual

stream in the lateral occipital and parieto-occipital regions.

On testing, these patients usually have recent memory impairment, although it is not the most salient feature of

their illness [33]. Acalculia, alexia, and anomia are also common early deficits in these patients [44]. Insight is

variably retained.

In most patients, neuropathologic examination reveals Alzheimer pathology with an exceptional distribution

involving visual association areas and even primary visual cortex [34,43,45]. Neuroimaging findings also usually

demonstrate this neuroanatomic pattern [36,44-46], although in one series of 12 patients with posterior cortical

atrophy, amyloid deposition on positron emission tomography demonstrated a distribution that was similar to

patients with typical AD [47]. A minority of patients with this syndrome have an alternative pathology, including

cortical Lewy bodies, tauopathy, and prion disease [43,45].

Primary progressive aphasia — Progressive nonfluent aphasia (PNFA) is usually associated with

frontotemporal dementia (FTD) rather than AD. However a significant percentage (up to one-third) are found at

autopsy to have AD instead [33,34,36,48-50]. Features suggesting FTD rather than AD include age of onset <60

years, prominent behavioral symptoms, and knife-edge frontotemporal atrophy at least in one series [51]. Other

case series have found that early memory impairment and a pattern of logopenia (frequent word-finding pauses

without major grammar or comprehension deficits) suggested AD rather than FTD; however neither of these

features are reliably predictive [11,36,50,52-54]. AD pathology is also sometimes found in patients with semantic

dementia, but this is less common [33,34]. (See "Frontotemporal dementia: Clinical features and diagnosis",

section on 'Progressive nonfluent aphasia' and "Frontotemporal dementia: Clinical features and diagnosis",

section on 'Semantic dementia' and "Frontotemporal dementia: Clinical features and diagnosis", section on

'Differential diagnosis'.)

Neuroimaging and neuropathologic studies in patients with PNFA attributed to AD demonstrate most prominent

involvement of the left perisylvian area [34,36,55].

Biparietal syndrome — Patients with the biparietal syndrome of AD often present with dyspraxia and have

difficulty completing simple bimanual tasks, such as dressing [33,56]. Other early clinical features can include

visuospatial disorientation, dysgraphia, and language impairment with semantic memory deficits (see 'Memory

impairment' above). Neuropathologic examination and neuroimaging studies demonstrate prominent involvement

of the parietal lobes bilaterally.

Others — A subset of patients with AD present with prominent deficits in executive function relative to

amnesia. In one case series of 88 such patients, MRIs revealed more thinning in the frontoparietal cortical

regions, the clinical course appeared to involve more rapid progression, and the prevalence of the APOE ε4

allele was lower compared to the more typical AD patients with prominent memory deficits [57].

Rare patients with clinical features consistent with corticobasal degeneration and the behavioral variant of

frontotemporal dementia are found at postmortem to have Alzheimer pathology [34,58].

Mixed dementias — It is not rare for Alzheimer pathology to coexist with other processes, including vascular

lesions, cortical Lewy bodies, argyrophilic grain disease, and Parkinson disease. The combination of two

pathologies can influence the clinical presentation and course of the disease and present diagnostic challenges

[59].

As expected, the most common combination is that of AD and vascular dementia. This is discussed in detail

separately. (See "Etiology, clinical manifestations, and diagnosis of vascular dementia", section on 'Mixed

dementia'.)

Another combination that is described is that of diffuse Lewy body and AD dementia [60-62]. In affected patients,

prominent memory loss can coexist with one or more features of dementia with Lewy bodies, including visual

hallucinations, fluctuations in sensorium, parkinsonism, and falls. (See "Clinical features and diagnosis of

dementia with Lewy bodies".)

CLINICAL COURSE — AD progresses inexorably. The progress of the disease can be measured with mental


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status scales such as the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating Scale (table

1). The clinical course, as measured by such scales, is not necessarily linear, however, a number of studies have

found that patients decline 3 to 3.5 points on average on the MMSE each year [63-66], with a minority (<10

percent) having a more rapidly progressive decline of 5 to 6 points on annual MMSE [67].

The reported mean survival after diagnosis of AD ranges from three to eight years [68-70]. Patients generally

succumb to terminal-stage complications that relate to advanced debilitation, such as dehydration, malnutrition,

and infection.

DIFFERENTIAL DIAGNOSIS — The most common disorders considered in the differential diagnosis of AD are

vascular dementia and other neurodegenerative dementias.

Vascular dementia is caused by either ischemic or hemorrhagic strokes. The most common form is due to

small vessel cerebrovascular disease. Diagnosis is most specific if there is a stroke-like course of illness,

neurologic signs of stroke on examination, and imaging evidence of stroke. However, the course of illness

may appear smoothly progressive, and there may be no elementary neurologic signs. (See "Etiology,

clinical manifestations, and diagnosis of vascular dementia".)

Dementia with Lewy bodies is the second most common type of degenerative dementia after AD. Clinical

features that help distinguish this from AD include prominent early appearance of visual hallucinations,

along with parkinsonism, cognitive fluctuations, dysautonomia, sleep disorders, and neuroleptic sensitivity.

(See "Clinical features and diagnosis of dementia with Lewy bodies".)

Frontotemporal dementia is a neuropathologically and clinically heterogeneous disorder characterized by

focal degeneration of the frontal and/or temporal lobes. Early alteration of personality, behavior, and

executive functioning distinguish this from AD. (See "Frontotemporal dementia: Clinical features and

diagnosis".)

DIAGNOSIS — Definitive diagnosis of AD requires histopathologic examination, which is rarely done in life

[71-73]. The diagnosis of AD in practice depends on clinical criteria. The role of laboratory and imaging

investigations is mainly to exclude other diagnoses. Neuropsychological testing may provide confirmatory

information and aid in patient management.

Clinicians should also consider potential contributors to the dementia syndrome such as adverse effects of

medication, depression, and metabolic disorders and deficiencies. (See "Evaluation of cognitive impairment and

dementia".)

Clinical assessments — The clinical criteria are based on a history of insidious onset and progressive course,

exclusion of other etiologies, and documentation of cognitive impairments in one or more domains. A detailed

cognitive and general neurologic examination is paramount. (See 'Clinical features' above.)

Many clinicians make use of standardized mental status scales, in particular, the Mini-Mental State Examination

(MMSE), to document the presence and progression of dementia [74,75]. It is important to use population-

appropriate reference scores in the MMSE [76]. The administration of this test is described separately. (See

"Evaluation of cognitive impairment and dementia", section on 'Mini-Mental State Examination'.)

A MMSE score between 20 and 26 is associated with mild functional dependence, such as difficulty managing

finances. Moderate AD (MMSE score between 10 and 20) is associated with more immediate dependency, such

as inability to drive, difficulty with hygiene and shopping, and remote memory impairment. Severe disease

(MMSE score under 10) correlates with a state of total dependence and need for constant supervision. Motor

impairments, notably gait and balance impairment, incontinence, and myoclonus, develop at this late stage, and

presage total debility. Some third-party payers require documentation of MMSE to support specific

pharmacologic interventions. (See "Treatment of dementia".)

Clinical criteria — Criteria for the diagnosis of probable AD dementia have been established by the National

Institute on Aging and The Alzheimer's Association [32,77].

Probable AD dementia is a syndrome of dementia defined by the following characteristics:


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Interference with ability to function at work or at usual activities

A decline from a previous level of functioning and performing

Not explained by delirium or major psychiatric disorder

Cognitive impairment established by history-taking from the patient and a knowledgeable informant; and

objective bedside mental status examination or neuropsychological testing

Cognitive impairment involving a minimum of two of the following domains:

impaired ability to acquire and remember new information

impaired reasoning and handing of complex tasks, poor judgment

impaired visuospatial abilities

impaired language functions

changes in personality, behavior or comportment

Other core clinical criteria include:

Insidious onset

Clear-cut history of worsening

Initial and most prominent cognitive deficits are one of the following:

amnestic presentation

nonamnestic presentations include either a language presentation, with prominent word-finding

deficits; a visuospatial presentation, with visual cognitive deficits; or a dysexecutive presentation, with

prominent impairment of reasoning, judgment and/or problem solving

No evidence of substantial concomitant cerebrovascular disease, core features of dementia with Lewy bodies,

prominent features of behavioral variant frontotemporal dementia or prominent features of semantic or

nonfluent/agrammatic variants of primary progressive aphasia, or evidence of another concurrent, active

neurologic or non-neurologic disease or use of medication that could have a substantial effect on cognition.

Possible AD includes the following clinical features [32]:

Atypical onset, presentation, or progression of dementia without known etiology

Presence of another potentially causative systemic or neurologic disorder that is not thought to be the

etiology of dementia in this case

Progressive deterioration in a single cognitive domain in the absence of any other etiology

These criteria are based on and are more restrictive than the 1984 NIDCD-ADRDA criteria [32]; all patients who

met criteria by the older criteria would meet the current criteria. The older criteria were confirmed at autopsy in

dementia research centers in 85 to 90 percent of cases [78,79].

The DSM-IV TR criteria for AD are also commonly used [80]:

The development of multiple cognitive deficits manifested by both:

Memory impairment

One or more of the following cognitive disturbances: aphasia, apraxia, agnosia, disturbance in

executive functioning

The cognitive deficits cause significant impairment in social or occupational functioning and represent a

significant decline from a previous level of functioning

The course is characterized by gradual onset and continuing decline


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The deficits are not due to another brain, systemic, or psychiatric condition

The deficits do not occur exclusively during the course of delirium

While less substantially validated compared with the NINCDS-ADRDA criteria, the DSM-IV criteria appear to

have similar accuracy [81,82].

Neuroimaging — Brain imaging, preferably with magnetic resonance imaging (MRI), is indicated in the

evaluation of patients with suspected AD [82]. Brain MRI can document potential alternative diagnoses including

cerebrovascular disease, other structural diseases (chronic subdural hematoma, cerebral neoplasm, normal

pressure hydrocephalus), and regional brain atrophy suggesting frontotemporal dementia.

MRI findings in AD include both generalized and focal atrophy, as well as white matter lesions. In general, these

findings are nonspecific. However, a number of investigators have correlated reduced hippocampal volume with

AD [83-86]. Because hippocampal volumes decline in normal aging, age-specific criteria are needed [83,84,87].

It is not clear that this finding adds to the accuracy of the diagnosis over the clinical assessment alone [88].

Some studies have suggested that MRI features may predict rate of decline of AD and in the future may guide

treatment decisions [64]. However, these findings require independent confirmation.

Functional brain imaging with [18F] fluorodeoxyglucose positron emission tomography (FDG-PET), functional

MRI (fMRI), perfusion MRI, or perfusion single photon emission computed tomography (SPECT) reveals distinct

regions of low metabolism and hypoperfusion in AD. These areas include the hippocampus, the precuneus

(mesial parietal lobes) and the lateral parietotemporal cortex [6,89-94]. Clinical studies suggest that FDG-PET

may be useful in distinguishing AD from frontotemporal dementia [95-97].

Amyloid PET tracers (eg, 11C-labeled Pittsburgh compound-B and others) that measure amyloid lesion burden

in the brain have been recently developed more recently and are under investigation as a tool to positively

diagnose AD in vivo, aid in prognosis, and differentiate AD from other causes of dementia [98-111]. While this

information may add value to the clinical assessment, these technologies are not universally available, and are

not part of the routine assessment of patients with AD, in part because there is no clear therapeutic imperative to

distinguish among the neurodegenerative dementias [112,113].

Other laboratory testing — Laboratory tests are not useful in the positive diagnosis of Alzheimer disease;

however, some laboratory tests are indicated to exclude contributing secondary causes. Recommended tests

include screening for hypothyroidism and vitamin B12 deficiency [82]. (See "Evaluation of cognitive impairment

and dementia".)

Some studies suggest that increased levels of tau protein and decreased levels of beta-amyloid protein ending at

amino acid 42 in cerebrospinal fluid (CSF) or plasma, increased CSF levels of visinin-like protein, and elevated

apoE and apoE4 plasma levels may have predictive value for AD in nondemented patients and in patients with

MCI, may also distinguish AD from other forms of dementia, and may identify subsets of patients with AD at risk

for a rapidly progressive course [114-132]. However, a role for these measurements in clinical practice has not

been established [133-136]. (See "Mild cognitive impairment: Prognosis and treatment", section on 'CSF

biomarkers' and "Mild cognitive impairment: Prognosis and treatment", section on 'Plasma biomarkers'.)

Genetic testing is not recommended in the routine evaluation of patients with AD. Genotyping with apolipoprotein

E adds marginally to the predictive value of clinical criteria for AD and may stratify risk of conversion of amnesic

MCI to AD, but both false positives and negatives occur [137,138]. Genetic testing for presenilin-1 mutations is

commercially available, but should be reserved for cases in which presenile dementia occurs in the setting of a

positive family history; this should not be performed in asymptomatic individuals without appropriate professional

genetic counseling.

Role of neuropsychological testing — Formal neuropsychological assessment can be helpful in the evaluation

of individuals with cognitive impairment and dementia. Cognitive testing under standardized conditions using

demographically appropriate norms is more sensitive to the presence of impairments, especially impairments of

executive function. Neuropsychological assessment can establish a baseline in order to follow the patient over

time. Neuropsychological assessment can also help differentiate between dementia and depression. Finally,

neuropsychological consultation can assess competencies and guide recommendations pertaining to driving,


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financial decisions, and need for increasing supervision. (See "Safety and societal issues related to dementia".)

While different causes of dementia can preferentially affect different cognitive domains, neuropsychological

testing has limited utility for differentiating among causes of dementia as there is substantial overlap in test

performance [139]. AD is characteristically associated with abnormalities in any or all cognitive domains, but

absence of recent memory impairment should raise the suspicion of another diagnosis. The salient

neuropsychological test features of other neurodegenerative dementias are discussed in individual topic reviews.

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Basics topics (see "Patient information: Dementia (including Alzheimer disease) (The Basics)" and

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SUMMARY AND RECOMMENDATIONS — Alzheimer disease (AD) is a neurodegenerative condition of

uncertain etiology. It is the most common cause of dementia.

AD is a disease of older age. Diagnosis before age 60 years is exceptional. The incidence increases

exponentially with age. (See 'Demographic features' above.)

Cognitive deficits in AD appear and progress insidiously. Memory impairment, specifically loss of memory

of recent events, is an essential feature of AD and is usually its first manifestation. Deficits in other

cognitive domains may appear with or after the development of memory impairment. Language function

and visuospatial skills tend to be affected relatively early, while deficits in executive function and

behavioral symptoms often manifest later in the disease course. (See 'Clinical features' above.)

Neuropsychiatric and behavioral symptoms are common in middle and late stages of AD. (See

'Neuropsychiatric symptoms' above and "Treatment of behavioral symptoms related to dementia".)

Noncognitive neurologic deficits (pyramidal and extrapyramidal motor signs, myoclonus, and seizures)

can occur in late stages of AD but are uncommon in early and middle stages. (See 'Other neurologic

deficits' above.)

Atypical presentations of AD have been described. These include a visual variant (posterior cortical

atrophy) and primary progressive aphasia. (See 'Atypical presentations' above.)

AD is inexorably progressive, but the rate of progression can vary. The average life expectancy has been

reported to be between three and eight years. (See 'Clinical course' above.)

The diagnosis of AD is made by clinical assessment. Diagnostic tests (laboratories and neuroimaging) are

performed primarily to exclude other diagnoses. (See 'Diagnosis' above.)

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Topic 5071 Version 10.0


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GRAPHICS

Clinical dementia rating (CDR): 0, 0.5, 1, 2, 3

Impairment None (0)Questionable

(0.5)Mild (1)

Moderate

(2)

Severe

(3)

Memory No memory

loss or slight

inconstant

forgetfulness

Consistent slight

forgetfulness;

partial

recollection of

events

Moderate

memory loss;

more marked

for recent

events;

defect

interferes

with everyday

activities

Severe

memory

loss; only

highly

learned

material

retained;

new material

rapidly lost

Severe

memory

loss; only

fragments

remain

Orientation Fully

oriented

Fully oriented or

slight difficulty

with time

relationships

Moderate

difficulty with

time

relationships;

oriented for

place at

examination;

may have

geographic

disorientation

elsewhere

Severe

difficulty with

time

relationships;

usually

disoriented in

time, often

to place

Oriented to

person only

Judgment and

problem

Solves

everyday

problems

and handles

business

and financial

affairs well;

judgment

good in

relation to

past

performance

Slight impairment

to solving

problems,

similarities,

differences

Moderate

difficulty in

handling

problems,

similarities,

differences;

social

judgment

usually

maintained

Severely

impaired in

handling

problems,

similarities,

differences;

social

judgment

usually

impaired

Unable to

make

judgments

or solve

problems

Community

affairs

Independent

function at

usual level

in job,

shopping,

volunteer

and social

groups

Slight impairment

in these activities

Unable to

function

independently

at these

activities

though may

still be

engaged in

some;

appears

normal to

casual

inspection

No pretense

of

independent

function

outside of

home;

appears well

enough to be

taken to

functions

outside of

family home

No pretense

of

independent

function

outside of

home;

appears too

ill to be

taken to

functions

outside a

family home

Home and

hobbies

Life at

home,

hobbies,

intellectual

interests

well

maintained

Life at home,

hobbies,

intellectual

interests slightly

impaired

Mild but

definite

impairment of

function at

home; more

difficult

chores

abandoned;

more

Only simple

chores

preserved;

very

restricted

interests,

poorly

maintained

No

significant

function in

home


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complicated

hobbies and

interests

abandoned

Personal care Fully

capable of

self care

Fully capable of

self care

Needs

prompting

Requires

assistance in

dressing,

hygiene

keeping of

personal

effects

Requires

much help

with

personal

care;

frequent

incontinence

Score only as decline from previous usual level due to cognitive loss, not impaired due to other factors.

Reproduced with permission from: Morris JC. The clinical dementia rating (CDR): Current version and

scoring rules. Neurology 1993; 43:2412. Copyright © 1993 Lippincott Williams & Wilkins.


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Clinical Manifestations and Diagnosis of Alzheimer Disease

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Transcript of Clinical Manifestations and Diagnosis of Alzheimer Disease