0221 Effect of Acutely Induced OSA During SWS on AD Plasma Biomarkers

Abstract Introduction OSA induces both sleep fragmentation and intermittent hypoxemia and has been associated with AD progression. We hypothesized that SWS-specific OSA can influence plasma AD biomarkers. Methods We developed a model of SWS-specific CPAP-withdrawal in subjects with AHI4% ≥ 20/hour to create 3 polysomnologically (PSG)-verified conditions per subject: 1) stable-SWS on CPAP, 2) SWS-fragmentation with intermittent hypoxemia (OSAsws), and 3) SWS-fragmentation with reduced hypoxemia (OSAsws+O2). We examined post-PSG morning plasma Aβ42 and Aβ40 by mass-spectrometry and plasma T-tau, P-tau181, NfL and GFAP by SIMOA in a study of 34 patients. Wilcoxon signed rank and Kruskal Wallace tests were used to compare SWS-specific OSA metrics and plasma measures across PSG conditions. Results In 34 patients (57 years, 32% female) CPAP withdrawal caused sleep disruption and recurrence of underlying OSA such that the OSAsws and OSAsws+O2 conditions caused significant increases in AHI4 and arousals during SWS [CPAP: 0 ±0, OSAsws: 16.1 ±15.7, OSAsws+O2: 16.2 ±12.0 in evts/hr, p< 0.0001], and arousal index during SWS [CPAP: 0.9 ±2.0, OSAsws: 11.7 ±14.3, OSAsws+O2: 11.7 ±15.5 in evts/hr, p< 0.0001] compared to CPAP treatment. Furthermore, the minimum SpO2 desaturation level of OSAsws was lower than OSAsws+O2 (OSAsws: 89.9 ±4.0, OSAsws+O2: 90.1 ±5.9 in % SpO2, p= 0.007). No change was observed between PSG conditions in Aβ42 (CPAP: 22.9 ±6.2, OSAsws: 21.3 ±6.2, OSAsws+O2: 21.2 ±6.8 in pg/mL), Aβ40 (CPAP: 232.3 ±39.9, OSAsws: 233.2 ±89.6, OSAsws+O2: 197.7 ±114.6), the ratio of Aβ42 to Aβ40 (CPAP: 0.10 ±0.01, OSAsws: 0.10 ±0.02, OSAsws+O2: 0.10 ±0.01), T-tau (CPAP: 3.1 ±0.3, OSAsws: 3.3 ±1.1, OSAsws+O2: 2.9 ±0.8 in pg/mL), P-tau181 (CPAP: 1.4 ±1.0, OSAsws: 1.5 ±0.5, OSAsws+O2: 1.6 ±0.9 in pg/mL), NfL (CPAP: 8.7 ±4.4, OSAsws: 6.0 ±3.0, OSAsws+O2: 7.8 ±6.0 in pg/mL), and GFAP (CPAP: 42.9 ±33.2, OSAsws: 30.9 ±25.6, OSAsws+O2: 39.5 ±36.9 in pg/mL). Conclusion Although we were able to recapitulate OSA in SWS, the degree of OSA severity was less than that on subjects’ diagnostic studies, and breathing was normal in N1, N2, and REM sleep, factors which possibly account for the lack of significant differences in biomarkers between conditions. Support (if any) R01AG056682, R01AG066870, RF1AG083975, R01AG080609, R01AG082278, K24HL109156, T32HL160511, K23AG068534, K25HL151912