0805 Alzheimer’s Disease Biomarkers Moderate the Effects of Obstructive Sleep Apnea Severity on Memory in Cognitively Unimpaired Older Adults

Abstract Introduction Obstructive sleep apnea (OSA) is linked to memory decline and elevated Alzheimer’s disease (AD) risk. Studies consistently show positive associations between sleep disturbances and AD biomarkers in preclinical cohorts, but it is unclear whether AD pathology alters how OSA severity impacts cognition. Here, we examined whether AD biomarkers in Cerebrospinal fluid (CSF) moderate associations between OSA severity and verbal memory. Methods Fifty-eight cognitively unimpaired older adults (61.4±6.3 years, 38 females, 23 AHI≥5) enriched for parental history of AD (n=45) and APOE4 positivity (n=15), and with no prior known history of OSA, underwent clinical polysomnography. Biomarkers were measured using exploratory RocheNeuroToolKit assays. Verbal memory was assessed with the Rey Auditory Verbal Learning Test (RAVLT). PROCESSv5.0 (model 1, SPSS) was used to examine moderating effects of phosphorylated tau-181 (p-tau), neurogranin, and α-synuclein on associations between OSA features (apnea-hypopnea index (AHI), respiratory-disturbance index (RDI), time with < 90% SpO₂) and RAVLT long delay recall performance, while adjusting for sex, age, time between assessments, education years, and body mass index (BMI). P-tau and neurogranin were logarithmically transformed and the reciprocal of α-synuclein was used to maintain normality, and False Discovery Rate (FDR) was implemented for multiple comparisons correction. Results Higher p-tau, neurogranin, and α-synuclein each moderate the association between greater OSA severity and worse long delay recall. Moderations were significant for AHI (p-tau b=–14.3, p< 0.05; neurogranin b=–10.2, p< 0.05; α-synuclein b=2924.1, p< 0.05), RDI (p-tau b=–20.1, p< 0.01; neurogranin b=–11.3, p< 0.05; α-synuclein b=3263.1, p< 0.05), and time < 90% SpO₂ (p-tau b=–15.9, p< 0.01; neurogranin b=–12.4, p< 0.01; α-synuclein b=3550.1, p< 0.01) relationships with RAVLT long delay recall. Conclusion These findings showed that the negative consequences of OSA severity on verbal memory were observed particularly in those with elevated CSF levels of ptau and neurodegeneration markers. These biomarkers may thus help identify those that are more vulnerable to OSA-related memory impairment in the preclinical stage. Support (if any) T35AG076424, T35DK128788, R56AG052698, R01AG027161, R01AG021155, P50AG033514, R01AG037639, K01AG068353, F31AG048732, UL1TR000427