The longitudinal association between dyslipidemia and cognitive trajectory

Document Type

Article

Abstract

BackgroundThe literature on dyslipidemia and cognitive trajectories among cognitively unimpaired (CU) persons remains inconclusive.ObjectiveTo investigate the association between baseline dyslipidemia and change in global and domain specific (i.e., memory, language, attention/executive function, and visuospatial skills) cognition in a population-based setting and whether the association differs by sex, age, or APOE ɛ4 carrier status.MethodsWe conducted a longitudinal study derived from the Mayo Clinic Study of Aging, involving 4236 CU persons aged ≥ 50 years. We ran linear mixed-effect models to examine baseline dyslipidemia in predicting longitudinal cognitive global and domain-specific z-scores adjusted for age, sex, education, medical comorbidity, repeated cognitive testing, and APOE ɛ4. We examined interactions among dyslipidemia, years since baseline, and separately by sex, age, and APOE ɛ4 carrier status.ResultsOver a median follow-up period of 6.4 years, CU individuals with dyslipidemia showed faster decline in z-scores of all domains, i.e., memory, language, attention/executive function, visuospatial and global cognition relative to CU individuals without dyslipidemia. Three-way interactions showed that dyslipidemia's effect on decline in z-scores of global cognition, attention and visuospatial skills was less pronounced in males than females. Higher age increased dyslipidemia's effect on decline in z-scores of attention but not global cognition or any other domain. APOE ɛ4 carrier status did not modify the effect of dyslipidemia on cognitive z-scores.ConclusionsDyslipidemia was associated with faster global and domain-specific cognitive decline over time in older community-dwelling individuals who were cognitively unimpaired at baseline. The effect of dyslipidemia on cognitive trajectories may be sex-influenced.

Medical Subject Headings

Humans; Male; Female; Dyslipidemias (psychology, genetics, epidemiology, complications); Longitudinal Studies; Aged; Middle Aged; Neuropsychological Tests; Cognition (physiology); Cognitive Dysfunction; Aged, 80 and over; Apolipoprotein E4 (genetics); Aging (psychology)

Publication Date

12-1-2025

Publication Title

Journal of Alzheimer's disease : JAD

E-ISSN

1875-8908

Volume

108

Issue

3

First Page

1104

Last Page

1114

PubMed ID

41129705

Digital Object Identifier (DOI)

10.1177/13872877251385255

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