1032 Association of Sleep Duration and APOE ε4 Status on Brain Regional Tau Deposition in Clinically Normal Older Adults

Abstract Introduction We examined interactive associations of sleep duration on regional tau-PET deposition in clinically-normal individuals, as a function of β-amyloid (Aβ), and apolipoprotein E (APOE) ε4 status. Methods This cross-sectional study analyzed preliminary data from 26 community-dwelling cognitively normal older-adults with baseline tau (18F PI2620) and Aβ (11C PiB) PET scans participating in NYU studies on sleep, aging and memory. Sleep duration was characterized as total sleep time (TST) using data from polysomnography (NPSG). Linear mixed effects models controlling for Aβ, age, sex, race, BMI and other sleep variables, examined a main association of TST with regional tau and a meta-region of interest, which was a composite of regions in the temporal lobe. Interactions between TST*Aβ, and TST*APOE ε4 on these regions were also examined Results Of the 26 subjects, 16 (61.5%) were females, 10 38.5% were Black/African-American, 14 53.8%, APOE ε4 carriers, and 3 11.5% individuals were Aβ+. The mean (SD) age was 66.5 (4.6) years, BMI was 26.0 (10.6) kg/m**2, and education was 16.4 (2.5) years. There was no clear association of TST with cortical tau in the combined meta-region involving the entorhinal and inferior temporal lobe (meta-analytic estimate: β = −0.010.01; 95% CI, −0.04 to 0.03, P =.16). However, TST by APOE ε4 interaction was significant for the combined meta-region (meta-analytic estimate: β = −0.060.02; 95% CI, −0.11 to -0.01, P =.03), right inferior temporal β right = −0.020.01; 95% CI, −0.04 to −0.00, P=.02), and bilaterally in the superior parietal β left = −0.200.08; 95% CI, −0.37 to −0.02, P=.03), β right = −0.030.01; 95% CI,−0.04 to −0.00, P=.04), cortical regions, suggesting a synergistic effect. TST by APOE ε4 interaction with regional tau trended in the left precuneus (β left = −0.010.01; 95% CI, −0.02 to 0.00, P=.07) and the left inferior temporal β left = −0.020.01; 95% CI, −0.03 to 0.00, P=.08) cortical regions. TST by Aβ interaction was not associated with regional tau. Conclusion APOE ε4 and sleep duration exhibited synergism in association with higher regional tau in cognitively-normal older adults. Larger studies are needed to delineate mechanisms and strata specific estimates. Support (if any) AASMBS-231-20, NIAK23AG068534, R01AG082278, AARG-D- 21-848397, BrightFocusA2022033S