Cognitive Function during the Prodromal Stage of Alzheimer’s Disease in Down Syndrome: Comparing Models

Abstract

Accurate identification of the prodromal stage of Alzheimer’s disease (AD), known as mild cognitive impairment (MCI), in adults with Down syndrome (MCI-DS) has been challenging because there are no established diagnostic criteria that can be applied for people with lifelong intellectual disabilities (ID). As such, the sequence of cognitive decline in adults with DS has been difficult to ascertain, and it is possible that domain constructs characterizing cognitive function in neurotypical adults do not generalize to this high-risk population. The present study examined associations among multiple measures of cognitive function in adults with DS, either prior to or during the prodromal stage of AD to determine, through multiple statistical techniques, the measures that reflected the same underlying domains of processing. Participants included 144 adults with DS 40–82 years of age, all enrolled in a larger, multidisciplinary study examining biomarkers of AD in adults with DS. All participants had mild or moderate lifelong intellectual disabilities. Overall AD-related clinical status was rated for each individual during a personalized consensus conference that considered performance as well as health status, with 103 participants considered cognitively stable (CS) and 41 to have MCI-DS. Analyses of 17 variables derived from 10 tests of cognition indicated that performance reflected three underlying factors: language/executive function, memory, and visuomotor. All three domain composite scores significantly predicted MCI-DS status. Based upon path modeling, the language/executive function composite score was the most affected by prodromal AD. However, based upon structural equation modeling, tests assessing the latent construct of memory were the most impacted, followed by those assessing visuomotor, and then those assessing language/executive function. Our study provides clear evidence that cognitive functioning in older adults with DS can be characterized at the cognitive domain level, but the statistical methods selected and the inclusion or exclusion of certain covariates may lead to different conclusions. Best practice requires investigators to understand the internal structure of their variables and to provide evidence that their variables assess their intended constructs.

Acquired mild cognitive impairment in adults with Down syndrome: Age‐related prevalence derived from single point assessment data normed by degree of intellectual disability

“…In larger, more general cognitive test batteries used in DS cohorts at high‐risk for dementia, it was shown that while there is clear evidence that AMCI can be identified at the cognitive domain level, statistical methodology and inclusion/exclusion of covariates can lead to differing results. 35 Similarly to the CAMCOG‐DS, 25 tailoring and validation of the NAID for the DS population specifically ensures sensitivity to the AMCI‐DS clinical phenotype. 36 …”

Timing of Alzheimer’s Disease by Intellectual Disability Level in Down Syndrome

“…To date, only a handful of large-sized studies have compared the trajectory of AD by premorbid ID level in DS [4,23,24]. These studies were limited in that they only stratified by mild versus moderate ID (excluded those with severe/profound ID), examined differences on only one or two cognitive measures, and analyses did not control for type of trisomy (full, mosaic, or translation) or apolipoprotein E (APOE) status (e.g., allele 4), genetic status, each which may have its own effect on the time course of AD clinical signs.…”

Down Syndrome: Neuropsychological Phenotype across the Lifespan

“…Two articles in this Special Issue, by Hom et al and Harp et al, examine the effectiveness of multiple measures of cognitive and behavioral functioning and the domains assessed in identifying dementia classification. The research by Hom et al [ 10 ] shows that cognitive functioning can be characterized at the cognitive domain level, with language, executive functioning and memory being candidates for most impacted domains. Building on this concept, Harp et al [ 11 ] developed an abbreviated test battery to identify individuals with DS at risk for AD.…”