Cognitive Dispersion Is a Sensitive Marker for Early Neurodegenerative Changes and Functional Decline in Nondemented Older Adults

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 relati...

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Bibliographic Details
Published in:Neuropsychology 2019-07, Vol.33 (5), p.599-608
Main Authors: Bangen, Katherine J., Weigand, Alexandra J., Thomas, Kelsey R., Delano-Wood, Lisa, Clark, Lindsay R., Eppig, Joel, Werhane, Madeleine L., Edmonds, Emily C., Bondi, Mark W.
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Aging
Aging - pathology
Aging - physiology
Alzheimer's Disease
Atrophy - pathology
Biological Variation, Individual
Biomarkers
Brain Size
Cerebral Atrophy
Cognitive Dysfunction - diagnostic imaging
Cognitive Dysfunction - pathology
Cognitive Dysfunction - physiopathology
Cognitive Impairment
Entorhinal Cortex
Entorhinal Cortex - diagnostic imaging
Entorhinal Cortex - pathology
Female
Hippocampus
Hippocampus - diagnostic imaging
Hippocampus - pathology
Human
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Mild Cognitive Impairment
Neurodegeneration
Neuropsychological Assessment
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Summary: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. General Scientific Summary Identification of early and reliable cognitive changes in the early stages of Alzheimer's disease (AD) is critical in order to target individuals at risk for significant neuropathologic and functional declines. Our findings suggest that cognitive dispersion may be a sensitive marker of brain changes and functional decline and have added utility above and beyond more conventional AD risk factors including age, genetic risk, and amyloid burden.
ISSN:0894-4105
1931-1559
DOI:10.1037/neu0000532