Intellectual Disability, Mild Cognitive Impairment, and Risk for Dementia

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  • Intellectual Disability, Mild Cognitive Impairment,and Risk for DementiaWayne P. Silverman*, Warren B. Zigman, Sharon J. Krinsky-McHale, Robert Ryan, and Nicole Schupf

    *Kennedy Krieger Institute and Johns Hopkins University School of Medicine, Baltimore, MD; and New York State Institute forBasic Research in Developmental Disabilities, Staten Island, NY, and Columbia University Medical Center, New York, NY, USA

    Abstract People with intellectual disability (ID) are living longer than ever before, raising concerns about old-age-associated disor-ders. Dementia is among the most serious of these disorders, and theories relating cognitive reserve to risk predict that older adultswith ID should be particularly vulnerable. Previous estimates of relative risk for dementia associated with ID have been inconsis-tent, and the present analyses examined the possible influence of variation in diagnostic criteria on findings. As expected, relaxationin the stringency of case definition for adults with ID increased relative risk, underscoring the importance of developing valid crite-ria for defining mild cognitive impairment and early dementia and distinguishing between the two in adults with ID. Once avail-able, these standards will contribute to more effective evidence-based planning.

    Keywords: dementia, incidence, intellectual disability, mild cognitive impairment, relative risk


    People with intellectual disability (ID) are living longer andmore fulfilling lives than ever before, and for the vast majority ofindividuals, their life expectancy approaches that of the generalpopulation (e.g., Strauss & Eyman, 1996). Nevertheless, lifespandevelopment for adults with ID (and other neurodevelopmentaldisorders) is atypical by definition, and their primary etiology ofID, as well as the effects of their lifelong experiences, may influ-ence vulnerability to old-age-associated impairments.

    Dementia is among the most serious concerns faced byelderly adults, potentially having devastating impacts on inde-pendence and quality of life. Dementia has many causes,Alzheimers disease being the most prevalent (see Jicha & Carr,2010), and increased risk associated with Down syndrome is welldocumented (see Zigman & Lott, 2007). However, the relation-ship between dementia risk and the presence/absence of ID perse is unclear and is the focus of the present set of analyses.

    Dementia is defined in the Diagnostic and Statistical Manualof Mental Disorders (4th edition, text revision; DSM IV-TR;American Psychiatric Association, 2000), as disorders . . . char-acterized by the development of multiple cognitive deficits(including memory impairment) that are due to the directphysiological effects of a general medical condition, to the per-sisting effects of a substance, or to multiple etiologies. Diagnosisis determined by the presence of impaired cognition sufficientin severity to have consequences for occupational or social

    functioning. In DSM V (American Psychiatric Association,2013), dementia has been replaced by major neurocognitivedisorder, but key features are largely unchanged in the reviseddefinition, requiring evidence of significant cognitive decline. . . in one or more cognitive domains . . . based on: (1) concernof the individual, a knowledgeable informant, or the clinician . . .and (2) a substantial impairment in cognitive performance, pref-erably documented by standardized neuropsychological testing,or, in its absence, another quantified clinical assessment. Whiledecline from a previously higher level of capability is a keyfeature that distinguishes dementia from ID, it is nevertheless thecase that preexisting cognitive impairments complicate diagno-sis. In fact, assessment methods and objective diagnostic criteriasuitable for the general population are typically uninformativefor adults with ID, and the need for consensus regarding evalua-tion methods and diagnostic criteria is now well recognizedwithin the developmental disabilities field (e.g., Burt & Aylward,1999; Janicki & Dalton, 2000; Silverman, Zigman, Kim,Krinsky-McHale, & Wisniewski, 1998).

    Risk for aging-associated dementia within the typicallydeveloping population rarely occurs prior to 60 years of ageand increases thereafter, with approximately 30% of the popu-lation over 80 affected (see Zaccai, Ince, & Brayne, 2006).Obviously, there is substantial heterogeneity in individual risk,and considerable progress has been made in determining thegenetic as well as the environmental factors that may contributeto this variability (e.g., Barnes & Yaffe, 2011; McMurtray, Clark,Christine, & Mendez, 2006). A thorough review of this topic isbeyond the scope of this paper, but one factor that may con-tribute to increased risk associated with ID per se has beentermed cognitive reserve (Stern, 2009). This is a hypotheticalconstruct presumed to mitigate the effects of old-age-associatedbrain pathology caused by various underlying diseases (e.g.,

    Received November 19, 2012; accepted July 3, 2013Correspondence: Wayne P. Silverman, PhD, Behavioral Psychology, KennedyKrieger Institute, 707 North Broadway, Suite 222s, Baltimore, MD 21205,USA. Tel: +1 443 923 2738; Fax: +1 443 923 2735;


    Journal of Policy and Practice in Intellectual DisabilitiesVolume 10 Number 3 pp 245251 September 2013

    2013 International Association for the Scientific Study of Intellectual and Developmental Disabilities and Wiley Periodicals, Inc.

  • Alzheimers, Parkinsons, and cerebrovascular disease). Stern(2009) argued persuasively that higher reserve, associated withhigh levels of cognitive capabilities, educational attainment,and literacy, should be protective and delay onset of dementia,while lower levels should increase vulnerability. If this is in factthe case, then ID should increase risk for old-age-associateddementia because of the lifelong presence of substantial cogni-tive and functional limitations that defines this diagnosis.

    Only two large studies to date have examined relative riskfor dementia in adults with ID 65 years of age and older(Strydom, Hassiotis, King, & Livingston, 2009; Zigman et al.,2004), both of which omitted adults with Down syndrome,given the high risk for Alzheimers disease within this specificsubpopulation. Zigman et al. relied primarily on analyses ofcumulative incidence and found no evidence of increased riskcompared with the general population (Saunders et al., 1993).In contrast, Strydom et al. focused on prevalence and found anincreased standardized morbidity ratio of 2.8 associated withpresence of ID.

    Strydom et al. considered several possible explanations forthis divergence in findings, including differences in sample size(Zigman et al. included 126 individuals with ID over 65, whileStrydom et al. had 142), bias in sampling method (enrollmentdid not consider dementia status in either study), and differencesin inclusion criteria (they suggested that Zigman et al. limiteddementia cases to Alzheimers disease, which was not actuallythe case). The two studies also employed different approachesto analyses of findings, were conducted in different countries(United States versus United Kingdom), and recruited partici-pants through two very different networks of services. Neverthe-less, these factors seem unlikely explanations for such aremarkable divergence in observed findings, and the presentanalysis focused on another possibility.

    Strydom et al. and Zigman et al. employed different methodsto evaluate and classify cases, and this seemed to be an intuitivelylikely source of the differences in study outcomes. Although con-vergence in case classifications should be expected, given thatboth studies relied on the judgments of highly experienced pro-fessionals, both groups were working without an establishedconsensus regarding evaluation methods and, most significantly,criteria for defining dementia objectively. Strydom et al. basedtheir case classifications on a single assessment of capabilitiesand combined cases with mild, moderate, and severedementia for analyses. Zigman et al. employed a substantiallydifferent method and based case classifications on individualprofiles of change over a period of up to 3 years. They also madea clear distinction between adults with dementia and their peersshowing milder declines comparable to mild cognitive impair-ment (MCI) within the general population (Petersen et al.,1999), while Strydom et al. made no mention of such a distinc-tion. This suggests that the difference in outcomes betweenStrydom et al. and Zigman et al. may have been caused by differ-ences in how they distinguished adults with mild dementia fromthose with MCI, a distinction that would be particularly difficultto make for adults with ID, especially without consideration ofobjective longitudinal findings. In fact, Strydom, Chan, Fenton,et al. (2013) recently reported a reexamination of the Strydomet al. (2009) cases approximately 3 years later. Using classifica-tion methods similar to their earlier study, they found that 33%

    of the original dementia cases who survived were no longerdemented, and 48% of the original group redefined operation-ally as having MCI improved in status at follow-up. Both find-ings imply imprecision in classifications, as did the reportedinterrater reliability of = 0.68.

    Conceptually, MCI is defined clearly enough as a state inter-mediate between normal cognition and dementia. Thus, adultswith MCI have experienced noticeable declines in cognition, butnot of sufficient severity to meet diagnostic criteria for dementia(Winblad et al., 2004). While explicit operationalization of thisdefinition remains in flux, even for older adults with typicallifespan development (e.g., Ganguli et al., 2011; Gauthier et al.,2006; Petersen et al., 1999; Winblad et al., 2004), there is clearconsensus that this condition often precedes old-age-associateddementia and can persist for an extended period of time. Withan estimated prevalence of between 8% and 42% for adults65 years of age and older (20.6% median prevalence in ninepopulation-based studies using various definitions of MCI;Ward, Arrighi, Michels, & Cedarbaum, 2012), approximatelythree times as many elderly adults have MCI as have frankdementia, the latter condition having an estimated prevalence of6.1% (Wimo, Winblad, Aquero-Torres, & von Strauss, 2003).

    Unfortunately, standard practices for diagnosing MCI inadults experiencing typical lifespan development are ill-suitedfor situations where substantial preexisting cognitive impair-ments are present, as is the case for adults with ID. In fact, veryfew studies have focused on MCI among adults with ID, andnone have proposed explicit diagnostic criteria applicable to thispopulation, although several reports have emphasized the sig-nificance of this condition (Ball et al., 2006; Ball, Holland,Treppner, Watson, & Huppert, 2008; Holland, Hon, Huppert, &Stevens, 2000; Krinsky-McHale, Devenny, Kittler, & Silverman,2008; Krinsky-McHale, Devenny, & Silverman, 2002; Nelson,Orme, Osann, & Lott, 2001; Urv, Zigman, & Silverman, 2010).With adults with ID who develop old-age-associated dementiavery likely to experience a progression of underlying diseasesimilar to that of their typically developing peers, the degree towhich cases with ID and MCI are distinguished from those withdementia would affect estimates of relative risk. If prevalence forthese two distinct conditions is unrelated to presence of ID, theexpected relative risk for dementia associated with ID would beoverestimated to the extent that those actually having MCIwould be misclassified as having mild dementia. On the otherhand, relative risk would be underestimated to the extent thatindividuals with ID and mild dementia would be misclassified ashaving MCI.

    The current study addressed this issue by reexamining thedementia classifications from the original Zigman et al. sample,employing operational definitions of dementia that varied instringency, and comparing estimates of cumulative incidencewith those for a sample representative of the general populationin one New York State county and matched for age and durationof surveillance. Importantly, these analyses were not intended todetermine the validity of any of the specific operational defini-tions of dementia or MCI under examination. While the presentresults may have implications for the eventual development ofbest-practice definitions of dementia and MCI for adults withID, the goals of these analyses are far more modest and arelimited to showing how varying the stringency of criteria

    Journal of Policy and Practice in Intellectual Disabilities Volume 10 Number 3 September 2013

    W. P. Silverman et al. Intellectual Disability and Dementia Risk


  • defining dementia can impact estimates for age-specific inci-dence and therefore relative risk.


    All procedures involved reexamination of findings for thesample described in Zigman et al. (2004), and readers arereferred there for details of the evaluation procedures. In brief,149 adults with ID without Down syndrome 65 years of age orolder were enrolled in a longitudinal study of aging and demen-tia.1 They were assessed at baseline and then on up to two subse-quent occasions approximately 18 months apart. The finalsample included only the 101 individuals who were evaluated onall three occasions (to provide a surveillance period clearly suffi-cient to observe objective indications of declining status), whowere younger than 85.5 years of age at baseline (too few caseswere over 85 years of age or older at baseline to provide stableestimates of population incidence), whose lifelong impairmentswere not of such severity as to preclude objective evaluation ofdecline (the case for three individuals), and who did not experi-ence a significant health-related concern clearly unrelated to anunderlying neuropathology that could account for functionaldecline (the case for four individuals).

    Assessments included informant interviews focused on adap-tive and maladaptive behaviors and neuropsychiatric problems,comprehensive reviews of clinical charts, and approximately2 h of cognitive assessments focused on both memory andnonmemory processes. Following each cycle of assessment, allfindings were examined during individual consensus case con-ferences, and the original dementia status for the cases includedin these analyses was determined as (1) not declining (other thanas expected with aging per se); (2) questionable/MCI, corre-sponding to presence of declines larger than expected with agingper se but of insufficient breadth or severity to be considereddementia; (3) possible dementia, corresponding to the presenceof substantial decline in multiple domains of cognition andfunctioning; or (4) definite dementia, where even more substan-tial declines are observed or with clear progression in decline.

    For the current study, those original dementia classificationsmade following the third assessment cycle were redeterm...


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