Longitudinal associations between lipid panel and cognitive decline modified by APOE 4 carrier status in biracial community-dwelling older adults: Findings from the Chicago health and aging project - PubMed (original) (raw)

doi: 10.1016/j.archger.2025.105825. Epub 2025 Mar 18.

Affiliations

PMID: 40179541
PMCID: PMC12058384 (available on 2026-07-01)
DOI: 10.1016/j.archger.2025.105825

Longitudinal associations between lipid panel and cognitive decline modified by APOE 4 carrier status in biracial community-dwelling older adults: Findings from the Chicago health and aging project

Ted K S Ng et al. Arch Gerontol Geriatr. 2025 Jul.

Abstract

Background: There have been contradictory findings on the associations between lipids and cognitive decline (CD), which may be attributed to the heterogeneity in the APOE4 carrier status, given APOE's lipid transportation roles. However, extant studies rarely examined the modifying effects of APOE4 carrier status on the associations between lipids and CD.

Methods: We analyzed the Chicago Health and Aging Project, a 20-year cohort study comprising older adults with lipid panel assayed, i.e., total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL), and longitudinal cognitive tests. We ran adjusted linear mixed-effects models, regressing cognitive test composite on each of the four lipids independently, first with the total sample and subsequently using interaction and stratified subgroup analyses, examining the modifying effects of APOE4 carrier status on the associations.

Results: 3,496 biracial community-dwelling older adults were recruited from the South side of Chicago (58% African American & 64% women; mean follow-up = 4.6 years). In the total sample, there was a borderline association between TG and CD, estimate (SD, p-value) = 0.0001 (0.0000,0.0565). No associations were detected with other lipids. In the interaction and subgroup analyses, only in ε4 carriers that higher TC levels were significantly associated with accelerated CD, -0.020 (0.009,0.035), whereas higher TG levels were significantly associated with decelerated CD, 0.001 (0.001,0.045). No modifying effects of ε4 carrier status were detected with other lipids.

Discussion: Specific lipids, i.e., TC and TG, were associated with CD only in the ε4 carriers, highlighting the potential importance of measuring APOE4 status to better inform risk prediction and treatment.

Keywords: Alzheimer's disease; Cholesterol; Cognition; Dementia; Epidemiology; Lipid.

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Conflict of interest statement

Declaration of competing interest K.D. and K.B.R. are funded by NIH research grants and reports no conflicts of interest. All other authors report no conflicts of interest. Author disclosures are available in the journal.

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Longitudinal associations between lipid panel and cognitive decline modified by APOE 4 carrier status in biracial community-dwelling older adults: Findings from the Chicago health and aging project - PubMed (original) (raw)