05/09/2018

1

Focus 2017Gregory D. Prichett, Psy. D.

gdpriche@gundersenhealth.org

Factors indicating an increased risk of Alzheimer disease in adults with ID

Incidence/prevalence and clinical features of dementia in adults with ID with an emphasis on Alzheimer disease in Down syndrome

Guidelines and procedures for assessing dementia in persons with ID

Most common genetic cause of intellectual disability (ID) resulting in significant limitations in intellectual function and adaptive behavior (ID Definition, AAIDD.org; n.d.) and classic physical stigmata

1/691 live births annually or ~6000 born in US each year (CDC, 2012)

More than 400,000 people are living with Down Syndrome in the US (National Down Syndrome Society, 2012)

1.2 million non-institutionalized adults had ID in 2010 (Brault, 2012)

05/09/2018

2

Brought about by a full or partial extra copy of chromosome 21

Extra genetic material alters course of development producing characteristics associated with DS

Trisomy accounts for 95% cases; translocation 4%, mosaicism ~1%

Most common cause of progressive dementia among older people

Insidious onset/gradual deterioration is typical but impairments can be abruptly unmasked by significant stressor or inter-current illness or injury

As disease progresses there is slow erosion of cognition resulting in increased functional dependence and eventual death

5.4 million Americans; 200,000 early onset (Alzheimer Association, 2016)

2:1 women to men Estimated 7.1 million by 2025; 13.8 million

by 2050 (Alzheimer Association, 2016)

05/09/2018

3

Triad of cognitive symptoms 2 signature brain lesions Functional isolation of the memory apparatus

Memory Loss-rapid rate of forgetting; significant disturbance in the ability to benefit from cues; compensatory confabulation

Anomia-”Tip-of-the-tongue” syndrome; compensatory circumlocution

Visual Spatial disturbances-geographical disorientation; constructional dyspraxia

Two common markers: amyloid plaques and neurofibrillary tangles

Changes begin in the medial temporal lobe and spread to the parietal and frontal cortices consuming most of the neocortex

global cerebral atrophy (prominent in temporal and parietal areas) and compensatory enlargement of ventricles

05/09/2018

4

Entorhinal cortex and hippocampi are structures in the medial temporal lobes that play a major role in memory formation

As AD progresses, input pathways from these structures are fundamentally disturbed

functional isolation of the structures from association areas of the neocortex

Well recognized association between DS and Alzheimer Disease

Increasing life expectancy of people with ID Adults with ID represent particularly

vulnerable segment of our population Increasing pressure on carers & support

system

Down (1866). Observations on an Ethnic Classification of Idiots.

Fraser and Mitchell (1876) described syndrome of premature aging and “precipitated senility” in DS

Alois Alzheimer (1906) A characteristic serious disease of the cerebral cortex. (Patient:Auguste D.)

Struwe (1929); Jervis (1948)-brain changes in AD also found in adults with DS

05/09/2018

5

Malamud (1972) “virtually all” DS adults showed key neuropathological changes characteristic of AD◦ Plaques were found across the life span as young as

8 yoa◦ Rates of deposition increased markedly age 35-40◦ Earliest deposition found in frontal lobe and

entorhinal cortex

Wisniewski and Rabe (1986) noted discrepancy between presence of neuropathological brain changes (age 30-40) and onset of clinical symptoms of dementia in Down Syndrome (mean age 50)

Lejeune (1959); Jacobs (1959)-uncovered genetic basis of DS, e.g. trisomy 21; Polani (1960)-translocation; Clark et al. (1961)-Mosaicism

Role of amyloid- “overexpression” of amyloid precursor protein (APP) gene leads to deposition of amyloid resulting in clinical/neuropathological changes in AD in DS

Gene for Beta Amyloid linked to region on Chromosome 21 which must be trisomic for full expression of DS (Goldgaber et al. 1987; Robakiset al. 1987; Tanzi et al. 1987; Korenberg et al. 1990)

05/09/2018

6

Adults with DS show the same pattern of tissue loss to that seen in the early stages of AD in the general population

Decline in neuronal density occurs before the onset of dementia

Well-recognized association between DS and AD

Increasing life expectancy of people with intellectual disability (ID)

ID people represent particularly vulnerable segment of our population

Increasing pressure on carers and support system

Persons with DS ID: 1920s-9 years; 1990s-56 years

Persons with Non-DS ID: 1930s-19 years; 1990s-66 years

05/09/2018

7

Multiple disabilities and level of ID influence life expectancy

Mild ID - 74.0 years Moderate ID – 67.6 years Severe ID – 58.6 years DS shorter life expectancy than Non-DS ID Higher mortality rates in early life due to

congenital heart disease and leukemia; later life due to dementia and premature aging

Well-recognized association between DS and AD

Increasing life expectancy of people with ID ID people represent particularly vulnerable

segment of our population Increasing pressure on carers and support

system

~640,000 adults with ID/DD >59 yoa Projected to nearly double to 1.2 million by

2030 when last of baby boomers reach 60 Majority of adults with ID live with family due

to choice or lack of alternatives; In a sizeable number of households the

primary caregiver is >59 yoa

05/09/2018

8

All Dementia AD71-79 4.97 2.3280-89 24.19 18.1090+ 37.20 29.60

Total 13.67 9.51Average Age Onset: 75 yearsAverage Duration: 8-10 years (3-20+)

Depends on age and presence of comorbid medical conditions

Age 60s-70s: 7-10 years Age 90s: 3 years or less

Mean duration between onset of symptoms and diagnosis: 2.8 years

05/09/2018

9

Age-risk doubles every five years for individuals greater than 65; ~50% after 85

Family History-first degree relatives; risk increases if more than one immediate family member has the disease

Genetic Risk Factors-APOE-e4; familial (autosomal dominant) AD

Traumatic brain injury

30-39 <3% 40-49 10-25%50-59 20-50% >59 30-75%

Average Age of Onset: 51.67 yrs (31-68) Prasher

& Krishnan (1993)

Average Duration: 3.5 – 10.5 yrs Dalton &

Wisniewski, (1990)

All Dementia AD>59 13.1 8.6>64 18.3 12.0

Average age of Onset: 67 years

05/09/2018

10

Down syndrome adults over the age of 40 Non-DS adults over the age of 59 Family history of Alzheimer disease History of head injury, especially if severe or

multiple head injuries

Adults with DS have highest rates of AD A substantial number remain dementia free

into their 70’s Onset of AD in DS is earlier than the general

population likely due to combination of factors-genetic predisposition, tendency toward premature aging, more aggressive form of the disease (?) versus delay in diagnosis

Rates of dementia in Non-DS ID adults are equal to if not higher than the general population

Onset and course approximate that of the general population

05/09/2018

11

Susceptibility to other causes of cognitive decline/conditions that mimic dementia

Premorbid Cognitive Deficits Heterogeneity of skills Dx Overshadowing Atypical Presentation Lack of professional training Lack of appropriate diagnostic criteria

Hypothyroidism-50% prevalence B12/folate deficiency-due to long-term use

of anti-seizure meds; oral contraceptives Depression/psychiatric impairment/life

stress-common in people with ID, often co-exists

Medication effects-narcotic analgesics, sedative hypnotics, anxiolytics, tricyclic anti-depressants, anti-psychotics

05/09/2018

12

Sleep Apnea-> chronic sleep deprivation; EDS Cardiac Abnormalities- common cause of

death in people with ID Infection- common cause of death Malignancy – common cause of death Pain/Joint Problems-> activity/functional

decline Sensory Impairments-40-77% hearing loss,

46% cataracts in DS individuals

All conditions can have effects on memory, cognition, mood and behavior and lead to deterioration in function

Frequent source of misdiagnosis Effects often assumed to be due to Alzheimer

disease Comprehensive and systematic medical

evaluation needed to rule out reversible causes

Adults with ID often lack the skills to perform standardized diagnostic tests of mental status

Compounded by limited ability to self-report, lack of consistent and reliable documentation of premorbid functioning

Makes it difficult to detect declines until pronounced

05/09/2018

13

Degree of cognitive and functional impairment observed depends on premorbid function

Often wide-ranging skills between individuals of the same level of ID

Different “starting points” make it difficult to detect change without a baseline for comparison

High prevalence of emotional, social and behavioral problems in individuals with ID at baseline, e.g. soliloquy (self-talk)

Behaviors have a strong “perceptual pull” –may overshadow the emergence of a true clinical syndrome

Changes in adaptive skills or behavior may predate early impairments in memory in adults with ID making it difficult to differentiate changes related to dementia versus new onset behavioral or psychiatric problem (or fluctuation in baseline behavioral problem).

05/09/2018

14

Many physicians and healthcare professionals lack training in the needs of individuals with intellectual disability across the life span (US Public Health Service, 2002)

Many clinicians and caseworkers are inadequately prepared to recognize symptoms or conduct diagnostic assessments of adults with ID who may be affected by dementia (Perkins & Moran, 2010).

Few specialists in this area

Current diagnostic systems do not address the unique features of dementia in adults with ID

DSM-IV/V and ICD-10 contain diagnostic categories for intellectual disability and dementia but not for intellectual disability with dementia

Assessments of adults with ID at a single point in time are inappropriate

Diagnosis of AD in adults with ID requires documentation of a change in status from a baseline level of function not a “normal level” of function

Major adaptations needed

05/09/2018

15

Conduct baseline assessments when healthy (DS< 36 yoa; Non-DS ID <50 yoa)

Follow longitudinally with periodic re-assessments

Document declines from “best level of performance”

Refer for formal diagnostic work-up when change noted

Employ direct assessment measures appropriate for use with adults with ID

Incorporate indirect assessments with carerswho know the affected individual well

There are no dx criteria specific to the diagnosis of dementia in individuals with ID

Consider use of ICD-10 criteria as they place greater emphasis on non-cognitive aspects of dementia and employ a two-step diagnostic process to aid in differential diagnosis

05/09/2018

16

If dementia suspected, all procedures involved in the assessment of dementia in the general population should be followed with necessary modifications to accommodate the adult with ID

For Consensus Recommendations see The National Task Group on Intellectual Disabilities and Dementia Practices (Moran et al. 2013).

Core Sxs of dementia in ID adults involves progressive loss of function in multiple cognitive domains similar to the general population

Presentation of dementia in ID is different(especially in DS) as personality and behavior change mark the early stages

05/09/2018

17

When memory or other cognitive decline occurs its progression is similar excepting for those tasks too difficult or complex to begin with

Manifestation of decline will depend on the premorbid level of IQ and memory and cognitive demands for everyday life

May be indirectly expressed by increase in dependence, loss of ability to carry out previously mastered ADLs

Forgetfulness for names and recent events Forgetfulness for location of everyday items Disorientation to time and temporal sequence

of events Spatial disorientation in getting around home,

neighborhood or work

Frequent reminders required to carry out daily tasks

Difficulty remembering the steps necessary to perform previously mastered tasks or directions

05/09/2018

18

Ability to assess depends on premorbid verbal skills and ability to meet task demands

Profound ID (MA<2) may preclude detection on standardized tests

Need to rely on informant report Use of neuro signs-myoclonic jerks, Sz

activity, abnormal posture/gait, rigidity, incontinence

If verbal skills well developed will see word-finding difficulty, dysnomia and diminished command following

If premorbid verbal skills poor will see decreased use of language progressing to total loss of verbal expression

Loss of previously acquired skills to read, write, count, draw and color

Decreased ability to carry out skilled purposeful motor acts necessary for basic ADLs-dressing, grooming, bathing, toileting, self-feeding

Inappropriate use of everyday objects

05/09/2018

19

General slowing in all areas Greater impairments to attention Decreased temporal and spatial orientation

Changes in emotional control, motivation and social behavior characterized by:◦ Emotional lability◦ Irritability◦ Apathy/inactivity◦ Stubbornness and coarsening of social behavior

Pervasive loss of interest/initiative in favorite foods, tv programs, past times, family activities and social gatherings

Slowness affecting all aspects of functioning-walking, eating, speaking, general movements

Withdrawal Isolation

05/09/2018

20

Crude, vulgar and unpleasant Oppositional/resistive behaviors, general

uncooperative mood, stubbornness Verbal/physical aggressiveness Change in baseline maladaptive behaviors-

usually increase but not always Loss of unique personality characteristics-

mischievousness, independent-minded, meticulousness, etc.

Easily angered or upset General moodiness and mood swings Nervousness, fearfulness and insecurity Need for more prompting and

encouragement Greater dependence on others hypochondriasis

With personality and behavior change there may be a corresponding decline in frontal-executive function (and related adaptive abilities) prior to the onset of memory impairment or full blown DAT

This has led some authors to conclude that a Frontotemporal dementia (FTD) represents the pre-clinical stage of AD, particularly in adults with DS

05/09/2018

21

Functional declines are first evident in more complex skills with progression to more fundamental basic skills later on

Decline in work productivity Household chores skills-table setting,

washing dishes, making meals, making bed, use of appliances

$ handling, banking and budgeting, ability to shop

Sense of direction, use public transportation Dependability with assigned activities

Initiative, persistence and perseverance in activities to structure and pass time

Basic arithmetic, counting and time telling Toileting, Bathing and personal hygiene Ability to eat, understand spoken language

and ambulate last to be affected

05/09/2018

22

Myoclonic jerks Late onset Sz or new type of seizure-50-80%

occurrence after diagnosis Parkinsonian features- (Postural

abnormalities, limb rigidity, slowness, shuffling of gait) ~20%

Urinary incontinence Pathological reflexes

Most screening instruments used for detection of dementia in general population are not suitable for people with ID due to floor effects

Standardized cut-offs can not be used for people with ID because they vary considerably in their cognitive abilities

05/09/2018

23

Age Range Ave. IQ (Range) Ave. MMSE (Range)Hosp. DD (13-58) 60.9 (42-69) 22.6Wksp (19-57) 53 (36-75) 22.7

(18-28)Act.Ctr. (19-57) 35.8 (15-63) 17.5

(5-29)

Of 62 demented and non-demented ID adults: 1) Only 34 cases (55%) could perform a MMSE2) 30 of those cases (95.2%) scored <243) 23 Ss(77%) did not have a dx of dementia4) Informant ratings (DMR;DSDS) proved far

superior in detecting dementia

Validated in persons with ID Assesses a range of skills-motor, language,

memory, conceptualization, general knowledge

8 questions require a verbal response Brief and easy to use Yields range of scores

05/09/2018

24

Psychometric properties are good Correlated with tools that measure functional

decline (e.g. DLSQ) at baseline and dx >sensitivity than MMSE to measure change Average annual rate of decline in dementia

group -1.8 points compared to -0.6 points in non-demented group

In a systematic review Zeilinger, Stiehl & Weber (2013) found 114 different instruments for assessment of dementia in ID◦ 79 direct assessment measures◦ 35 informant based measures◦ 4 Test batteries◦ A number of tests in common use were neither

designed for assessment of dementia nor for persons with ID (!!!).

Direct assessment measures document cognitive changes; carers often unreliable in reporting cognitive functioning

Indirect assessments are necessary to document that any declines in cognitive function are significant enough to affect daily functioning

05/09/2018

25

Reliance on carers who may be developing cognitive difficulties limiting accuracy

Carers may know subject too well or not enough to be objective

While many include cognitive domains, does not assess cognition directly

Superior to direct measures and thus preferred with more severe ID (MA<5)

Assesses cognition directly Floor effects to a varying degree Limited use with severe disability and/or

limited verbal ability Combination of the two likely to provide the

highest sensitivity and specificity

Dementia Scale for Down Syndrome (DSDS) -Gedye (1995)

Dementia Questionnaire for Mentally Retarded Persons (DMR)-Evenhuis (1992)

Camdex-DS-Ball et al. (2004) Dementia Screening Questionnaire for

Individuals with Intellectual Disabilities (DSQIID)-Deb et al. (2007)

05/09/2018

26

Test of Severe Impairment (TOSI)-Albert and Cohen (1992)

CAMCOG-DS-Ball et al. (2004) Institute for Behavioral Research Evaluation of

Mental Status (IBREMS)-Wisniewski and Hill (1985)

Offers carers and staff a resource to record changes in cognitive and adaptive function known to be associated with dementia

Not an assessment/dx instrument but an “administrative screen” that provides info to begin conversations with HC providers

Adapted from DSQIID (Deb, 2007)

Relevant Demographics Ratings of Health, MH and life Stressors Review multiple domains of function Survey of chronic health conditions Signal items

05/09/2018

27

Select only those designed or adapted for use in detecting dementia in ID

Must be reliable/valid, sensitive to change early and through out the later stages of dementia and measure a wide range of cognitive domains

Consider Practical Issues-time requirements, level of expertise required to administer, score and interpret tests

Adults with ID experience the full range of mental illnesses

Psychiatric disorders 2-4x more common in ID than the general population

05/09/2018

28

A complex process High prevalence of emotional/behavioral

disturbance at baseline Baseline intellectual and psychosocial deficits

influence the presentation of symptoms and limit use of traditional diagnostic criteria

Diagnostic Overshadowing (Reiss et al., 1982) Pathoplastic Factors (Sovner, 1986)◦ Psychosocial Masking-unsophisticated clinical

presentation due to limited life experiences◦ Baseline Exaggeration-worsening of pre-existing

maladaptive behaviors◦ Cognitive Disintegration-tendency to become

emotionally/cognitively disorganized under stress◦ Intellectual Distortion-lack of verbal/conceptual

skills to report psychological status

Share many overlapping symptoms with dementia

Strong association with cognitive and functional decline

Psychiatric impairments (esp. depression) may serve as a prodrome for dementia

Differential diagnosis critical to avoid misdiagnosis and inappropriate treatment

05/09/2018

29

Anxiety – 1-25% Depression – 5-67% Manic Depression – rare (doubtful) Schizophrenia - 21-24% Personality Disorder – 15-35%

Most prevalent; more common in DS Often presents as behavioral change◦ Withdrawal◦ Loss of adaptive living skills◦ Observable changes in mood◦ Concurrent severe behavioral problems common◦ Psychotic or psychotic-like features also common

40/272 Adult DS Center patients dx’d with depression

24% comorbid hypothyroid or vitamin B12 deficiency

35% comorbid anxiety disorder 34% comorbid behavior disorder/sxs 33% obsessive compulsive sxs

05/09/2018

30

Typical pattern involved mild-moderate impairments in social relations, work and/or school functioning and/or daily living skills

Symptoms lasted on average 1 year

Debilitating impairments in 2 functional areas-social relations, work or school activity or ADLs

Typical pattern: isolation, job loss or excessive work/school absence, significant reduction in self-care or DLS

Psychotic features common-extreme withdrawal, trance-like stupor, delusions, hallucinatory-like conversations with self and imaginary others

Sxs lasted an average of 28 months (24-36 mos)

While self-talk found to be common for many clinic patients, the incidents of such behaviors were:◦ More numerous, extreme and more public◦ Conversations tended to be more animated, angry

in content◦ Seemingly oblivious to the presence of others or

social convention

05/09/2018

31

Differential diagnosis is enhanced when criteria are adjusted to take into account their intellectual and psychosocial deficits; when diagnostic ”behavioral equivalents” are used; care is taken to rule out all other medical and psychiatric conditions, and by paying careful attention to course.

As a group adults with ID are exquisitely sensitive to stress

A common trigger for psychological disorders especially depression

Vulnerable to breakdowns in reality testing-> transient psychotic symptoms

Loss most common and impactful trigger for depression

Carers often do not believe ID adults understand the concept of death and minimize its effects

ID Adults report sadness even if they do not understand the concept of death

Effects of loss are additive

05/09/2018

32

No widely accepted diagnostic schemes in use Two promising multiaxial systems: DC-LD (Royal

College of Psychiatrists, 2001); DM-LD (Fletcher et al. 2007).

A number of diagnostic-specific schemes have been proposed for depression (Sovner and Hurley, 1982; Smiley and Cooper, 2003; Burt, 1999) manic depression (Sovner and Hurley, 1982), anxiety (McGuire and Chicoine, 1996), and schizophrenia (Meyers and Pueschel, 1993) that may be helpful.

Include all standard aspects of psychiatric/psychologic assessment

Additional biopsychosocial and developmental considerations

A number developed for adults with ID Employ normative comparisons and in some

cases self vs informant ratings Not typically designed for adults with

possible comorbid dementia Could be used to assess change in status

over time especially if baseline established when stable/healthy

05/09/2018

33

Emotional Problems Scale (Prout and Strohmer, 1991)

Reiss Screen for Maladaptive Behavior (Reiss, 1988)

Diagnostic Assessment for Severely Handicapped Scale-2 (DASH-2); (Matson, Gardner, Coe & Sovner, 1991)

Assessment Instrument for Anxiety, Depression and Mood Scale (ADAMS); (Esbensen, Rohahn, Aman & Ruedrich, 2003)

Psychopathology Instrument for Mentally Retarded Adults (PIMRA); (Senatore, Matson & Kazdin, 1984)

Individuals with intellectual disability are living longer and as such at increased risk for age-related conditions including dementia

Detecting dementia in ID populations is difficult due to their premorbid cognitive and psychosocial deficits, tendencies for dementia to present atypically and their susceptibility to medical problems that mimic dementia.

Personality and behavior changes often predate the onset of memory or other cognitive loss in ID dementia.

There are no criteria specific to the diagnosis of dementia in ID.

Use of ICD-10 diagnostic criteria are recommended as they place greater emphasis on non-cognitive aspects of dementia in ID.

05/09/2018

34

Standard assessment measures used “at a single point in time” to document declines in the general population presume a normal level of premorbid function and thus are inappropriate for use with this population as many adults with ID lack the skills to perform these tasks at baseline.

Longitudinal assessment with measures appropriate for use with ID adults is required to document changes in status from a baseline or “personal best” level of function

Baseline screenings ideally should be done when healthy and periodically repeated

Comprehensive work-up should be initiated when change is detected.

The diagnosis of dementia in adults with ID is further complicated by the high prevalence of psychiatric and behavioral disorders that can mimic or compound the symptoms of dementia.

05/09/2018

35

Differential diagnosis can be enhanced by taking into account the adaptive and expressive limitations of adults with ID, utilizing diagnostic behavioral equivalents, ruling out other medical causes and by paying careful attention to course.

A number of neuropsychological assessment measures have been developed to aid in the clinical diagnosis of dementia in adults with ID

Combining direct assessment measures and observer rated scales is likely to provide the highest sensitivity and specificity

Next Steps Questions/Comments

05/09/2018

36

Janicki, MP & Dalton, AJ (eds). (2013). Dementia, Aging and Intellectual Disabilities: A Handbook. Routledge: New York.

Jokinen, N., Janicki, M.P., Keller, S.M., McCallion, P., Force, L.T. and the National Task Group on Intellectual Disabilities and Dementia Practices. (2013). Guidelines for structuring community care and supports for people with intellectual disabilities affected by dementia. Journal of Policy and Practice in Intellectual Disabilities, 10(1), 1-24.

Moran, J. A., Rafii, M. S., Keller, S. M., Singh, B. K., Janicki, M. P. (2013). The national task group on intellectual disabilities and dementia practices consensus recommendations for the evaluation and management of dementia in adults with intellectual disabilities. Mayo Clinic Proceedings, 88(8), 831-840.

Moran, J. (2013). Aging and Down Syndrome: A Health and Well-being Guidebook. National Down Syndrome Society. www.ndss.org.

Prasher, V. P. (Ed). (2009) Neuropsychological assessments of dementia in down syndrome and intellectual disabilities. London: Springer-Verlag.