0825 Sex-Specific Associations Between Apolipoprotein epsilon-4 Allele Status and Sleep Propensity on the Multiple Sleep Latency Test

Abstract Introduction The apolipoprotein epsilon-4 (APOEε4) allele is a key risk factor for sporadic Alzheimer's Disease. Women APOEε4 carriers are more likely to develop neurocognitive impairment than men, suggesting sex-specific effects of the allele on brain function. Since sleepiness has been associated with risk of cognitive decline, this study examined associations between objective sleep propensity quantified by the multiple sleep latency test (MSLT), APOEε4 status, and sex in a population-based sample. Methods 1,028 individual MSLTs performed in 723 participants in the Wisconsin Sleep Cohort (WSC) study (age 60.4±8 years; 48% female) were utilized. Mixed linear models with repeated observations were utilized to test associations between MSLT mean sleep latency (outcome), APOEε4 status (modeled ordinally as 0, 1 or 2 ε4 alleles), and sex*APOEε4 interactions, with additional covariates (age, body mass index, antidepressant use, sedative use, stimulant use, caffeine/nicotine prior to MSLT naps, circadian preference, and apnea-hypopnea index) included in models. Results In fully adjusted models, a significant sex*APOEε4 interaction was observed (p=0.012). Fully adjusted analyses stratified by sex demonstrated a significant association of APOEε4 with mean sleep latency in men (β=-1.32 minutes/per APOEε4 allele), p< 0.001), that was not observed in women (β=0.067, p=0.89). Conclusion APOEε4 is associated with significantly reduced mean sleep latency on the MSLT among men participating in the WSC. Further research is indicated to determine if this observation extends to younger age groups or central disorders of hypersomnolence. Support (if any) This study was supported by grants from the US National Institutes of Health and the National Institute on Aging (R01AG079352 and R01AG058680).