1042 Influence of OSA Severity on the Association of Global Amyloid and Regional Tau-PET Burden

Abstract Introduction We examined the association of OSA severity with regional tau-PET deposition in clinically normal individuals, as a function of β-amyloid (Aβ), race and apolipoprotein E (APOE) ε4 status. Methods Cross-sectional analysis of preliminary data from 26 (16 Whites and 10 Blacks matched on AHI4%, age, BMI and educational level) community-dwelling cognitively normal older-adults with baseline tau (18F PI2620) and Aβ (11C PiB) PET scans. OSA severity was characterized using AHI4%. Linear mixed effects models controlling for Aβ, age, sex, race, BMI and other sleep variables, examined a main association of OSA with regional tau and a meta-region of interest, which was a composite of regions in the temporal lobe. Interactions between OSA*Aβ, OSA*Race, and OSA*APOE ε4 on these regions were also examined. Results Of the 26 subjects, 16 (61.5%) were females, 14 APOE ε4 carriers 53.8%, and 3 individuals 11.5% 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. OSA severity was associated with cortical tau in the combined meta-region involving the entorhinal and inferior temporal lobe (meta-analytic estimate: β = −0.120.05; 95% CI,−0.23 to −0.00), and regional tau in the superior parietal (β left = −0.050.02; 95% CI,−0.10 to −0.01; β right = −0.050.02; 95% CI,−0.09 to −0.00), left parahippocampal (β = −0.050.02; 95% CI,−0.09 to −0.00), and right precuneus (β = −0.040.01; 95% CI,−0.06 to −0.01) cortical regions, P = .04 for all. A race by OSA severity interaction was significant for the left superior parietal (β White, AHI4% = −0.060.01; 95% CI,−0.12 to −0.00), and left parahippocampal (β White, AHI4% = −0.010.03; 95% CI, −0.03 to −0.00) and (β Black, AHI4% = −0.040.01; 95% CI,−0.06 to −0.00) regions, P = .05 for all. OSA severity by APOE ε4 interaction was not associated with regional tau. Conclusion OSA severity is associated with regional tau-PET deposition in clinically normal individuals, regardless of APOE ε4 status, and this association differed by race in certain brain regions. These findings highlight OSA as a unique disease model for examining racial differences in Alzheimer disease risk. Support (if any) AASMBS-231-20, NIAK23AG068534, L30-AG064670, R01AG082278, RF1AG083975, AARG-D- 21-848397, BrightFocusA2022033S