0857 OSA Treatment with PAP Reduces Locus Coeruleus-Hippocampal Resting-State Functional Connectivity on 7T MRI in Cognitively Normal Older Adults

Abstract Introduction The locus coeruleus (LC) is a structure important in both sleep/wake regulation and memory/cognition but its resting state functional connectivity (FC) to memory-relevant structures as a function of OSA and its treatment has not been assessed. Methods Here, we examined the LC using 7T MRI with a computational LC localization and segmentation algorithm in 30 cognitively normal older subjects (55-85 yo): 17 with a new OSA clinical diagnosis (AHI4%≥5) and 13 from the community without sleep complaints in which 5 had incidentally-identified OSA. Twelve of the OSA subjects elected positive airway pressure (PAP) therapy and returned 3-months later for a repeat 7T-MRI. Median PAP adherence was 4.3 ± 4.1 hours. Results Across most regions—including the right inferior parietal cortices, precuneus, and left inferior parietal cortex—individuals with OSA exhibited higher LC connectivity than their non-OSA counterparts, with small to moderate effect sizes (Cohen’s d = 0.28–0.39). The largest difference between OSA and non-OSA subjects was observed in the right hippocampus, where LC–hippocampal FC was markedly greater in the OSA group compared to the non-OSA group (Fisher’s z-score OSA: 0.025 ± 0.112, non-OSA: -0.010 ± 0.091, Cohen’s d = 0.66). In 12 individuals with completed 7T-MRI scans both before and after 3-months of PAP use, there were significant regional differences in FC with the bilateral LC (seed-based connectivity). Regions included the right hippocampus, bilateral superior and inferior parietal regions, right medial temporal region, left precuneus. Specifically, the FC of the LC with the right hippocampus exhibited a significant reduction from untreated (baseline) to 3-months of PAP use (pFDR corrected<.05, k cluster size>50). Conclusion LC resting state FC with anterior brain structures, particularly the hippocampus, is higher is subjects with OSA than without OSA, potentially suggesting LC hyperactivity. We present some of the first evidence that treatment of OSA through PAP can potentially decrease LC-hippocampus FC at rest, encouraging exploration of the functional impacts on memory. Support (if any) AASMF Bridge award, AARGD award, NIH TART R01 (R01 AG066870), BLOSOM RF1, R01 AG080609