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Published on: September 20, 2018
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Clinical Manifestations.
Katherine J Bangen1,2, Lauren C Edwards3, Fini Chang2
1University of California, San Diego, La Jolla, CA, USA.
Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
Summary
Cognitive intraindividual variability (IIV) predicts faster functional decline in everyday life, especially for those with amyloid-beta (Aβ) or apolipoprotein E (APOE) ε4. This highlights IIV as a key marker for Alzheimer's disease risk.
Area of Science:
- Neuroscience
- Gerontology
- Cognitive Science
Background:
- Cognitive intraindividual variability (IIV) is linked to increased risk of mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia.
- Previous research shows IIV predicts future declines in everyday functioning.
- The role of IIV as a risk marker in specific groups like amyloid-beta (Aβ) positive or apolipoprotein E (APOE) ε4 carriers is less understood.
Purpose of the Study:
- To investigate the moderating effects of Aβ status and APOE genotype on the association between IIV and everyday functioning.
- To determine if IIV is a sensitive marker of decline in specific at-risk populations.
Main Methods:
- Utilized data from 736 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants without dementia.
- Assessed cognitive performance, everyday functioning (Functional Assessment Questionnaire), Aβ deposition (PET imaging), and APOE genotype.
- Employed linear mixed effects models to examine interactions between IIV, Aβ status, APOE ε4 status, and time on functional decline.
Main Results:
- Higher baseline IIV predicted a faster rate of decline in everyday functioning for Aβ+ participants compared to Aβ- participants.
- Higher baseline IIV also predicted a faster rate of decline in everyday functioning for APOE ε4 carriers compared to non-carriers.
Conclusions:
- Greater cognitive IIV is associated with accelerated functional decline, particularly in individuals who are Aβ+ or APOE ε4 carriers.
- IIV may serve as a sensitive biomarker for brain changes and functional decline, offering additional predictive value beyond traditional risk factors.
- Further research is needed to refine IIV operationalization and validate its use in diverse older adult populations at risk for cognitive decline.
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