Neurology
Sleep Health in Late Life and APOE4-associated Risk for Neuropathologic Lesions at Death: the Honolulu-Asia Aging Study Tianyi Huang* Tianyi Huang Huang Huang Huang National Institute on Aging
Introduction: Apolipoprotein E ε4 (ApoE4) drives lipid dysregulation and neurotoxic protein accumulation, contributing to brain lesions. Population-based evidence is limited on whether sleep health mitigates APOE4-associated neuropathologic risk.
Methods: In the Honolulu-Asia Aging Study, 533 Japanese-American men completed ≥2 sleep assessments across four exams (1991–2000) and participated in the autopsy substudy, with APOE4 genotyping available. We created a cumulative average sleep health score (SHS; range 0–5) from repeated questionnaires, assigning 1 point for each favorable sleep factor: sleep duration of 6–8 hrs, no insomnia symptoms, no loud snoring, no daytime sleepiness, and moderate napping (>0 but <60 min). Using multivariable logistic regression, we examined associations between APOE4 and neuropathologic outcomes, including vascular lesions (microinfarcts, lacunar infarcts), Alzheimer’s-related pathology (neuritic plaques [NPs], neurofibrillary tangles (NFTs), Braak stage), Lewy bodies (LBs), and generalized brain atrophy, overall and stratified by SHS categories.
Results: Mean (SD) baseline age was 77.4 (4.3) years; the interval between the last sleep assessment and death was 4.7 (3.3) years; 21.4% were APOE4 carriers. After adjustment for baseline age, age at death, education, and cognitive scores, APOE4 carriers had higher odds of microinfarcts, NPs, NFTs, Braak stage V/VI, and LBs, with no associations for lacunar infarcts or brain atrophy. Associations were stronger among participants with poorer sleep health. For example, the OR (95% CI) between APOE4 and NFTs was 4.55 (1.44, 14.38), 2.37 (1.27, 4.41), and 1.33 (0.54, 3.29) in poor, fair, and good sleep health groups, respectively. Further adjustment for behavioral and cardiovascular factors yielded similar results.
Conclusions: Better sleep health may attenuate APOE4-associated risk for multiple brain lesions, suggesting sleep as a potentially modifiable factor relevant to genetic vulnerability.