Cognitive dispersion is a sensitive marker for early neurodegenerative changes and functional decline in nondemented older adults

Abstract

Objective: Intraindividual cognitive variability (IIV), a measure of within-person variability across cognitive measures at a single time point, is associated with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Little is known regarding brain changes underlying IIV, or the relationship between IIV and functional ability. Therefore, we investigated the association between IIV and cerebral atrophy in AD-vulnerable regions and everyday functioning in nondemented older adults.

Method: 736 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants (285 cognitively normal [CN]; 451 MCI) underwent neuropsychological testing and serial MRI over 2 years. Linear mixed effects models examined the association between baseline IIV and change in entorhinal cortex thickness, hippocampal volume, and everyday functioning.

Results: Adjusting for age, sex, apolipoprotein E genotype, amyloid-β positivity, and mean level of cognitive performance, higher baseline IIV predicted faster rates of entorhinal and hippocampal atrophy, as well as functional decline. Higher IIV was associated with both entorhinal and hippocampal atrophy among MCI participants but selective vulnerability of the entorhinal cortex among CN individuals.

Conclusions: IIV was associated with more widespread medial temporal lobe (MTL) atrophy in individuals with MCI relative to CN, suggesting that IIV may be tracking advancing MTL pathologic changes across the continuum of aging, MCI, and dementia. Findings suggest that cognitive dispersion may be a sensitive marker of neurodegeneration and functional decline in nondemented older adults. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Figure 1

Baseline IIV Predicts Entorhinal and Hippocampal Atrophy and Functional Decline Line graphs displaying model predicted values, controlling for age, sex, apolipoprotein E ε4 genotype, PET amyloid-β positivity, and mean level of cognitive performance (and additionally adjusting for education for the model with functional abilities as the depending variable) are shown for (A) entorhinal cortex, (B) normalized hippocampal volume, and (C) Functional Assessment Questionnaire. For visual comparison, the graphs display results for high IIV levels in comparison with low IIV levels which were determined by a median split of the values in the analytic sample (Low = IIV < 0.8195; High = IIV ≥ 0.8195). Lower cortical thickness and hippocampal volume indicate reduced thickness and volume, respectively, (i.e., increasing atrophy). Higher FAQ scores indicate greater functional difficulty. Error bars represent the standard error of the mean.