1030 APOE Genotype and Sleep Architecture

Abstract Introduction APOE4 genotype, a robust genetic risk factor for Alzheimer’s Disease, is associated with reduced functional connectivity of the basal forebrain, one of the key regulators of sleep and wakefulness. The objective of this study was to examine the association between APOE4 genotype and sleep architecture. Methods This study included 1,793 participants aged 65-85 from the Sleep Heart Health Study (SHHS) who completed in-home, overnight polysomnography. Primary predictor was APOE4 allele carrier status: non-carriers (reference), heterozygotes and homozygotes. Outcomes included the following three characteristics of sleep architecture: time spent in slow wave sleep (SWS), time spent in rapid eye-movement sleep (REM) and the number of arousals per hour. We used linear regression to examine the association between APOE4 carrier status and each sleep architecture characteristic, adjusting for age, sex, marital status, and educational attainment. Results The sample included 9.5% people of color and 52.7% women. Median age was 73 (interquartile range = 69,77). Average duration of SWS and REM (minutes/night) by APOE4 genotype was: 62.7 and 68.7 (non-carriers); 63.0 and 67.6 (heterozygotes); and 63.0 and 70.7 (homozygotes). Average number of arousals among non-carriers, heterozygotes, and homozygotes was 18.5, 17.2, and 16.2 times/hour, respectively. Linear regression models showed that APOE4 carrier status was not associated with time spent in SWS or REM. The number of APOE4 alleles showed an inverse linear trend with arousals/hour, (β=-0.77 95%CI=-1.96,0.42 in heterozygotes; β=-4.25 95%CI=-8.01,-0.50 in homozygotes). Additional analyses using other sleep architecture measures, including the proportion of time spent in SWS or REM, SWS or REM duration/hour, wake after sleep onset (WASO), total sleep duration, and time spent in non-SWS sleep, all yielded non-significant results, except for total arousals/night, which exhibited an inverse linear trend with the number of APOE4 alleles (β=-3.64 -10.44,3.16 in heterozygotes; β=-22.52 -43.97,-1.07 in homozygotes). Conclusion Contrary to our expectations, APOE4 carriers did not show reduced sleep quality across various indices, including time spent in SWS, REM or WASO. They also showed reduced number of arousals. Our findings suggest that non-respiratory sleep problems may not be the primary pathway leading to an increased burden of Alzheimer’s disease in APOE4 carriers. Support (if any) SHHS was supported by: UOIHL53940, UOIHL53941, UOIHL53938, UOIHL53916, UOlHL53934, UOIHL53931, UOIHL53937.