McCarter, SJ

Abstract Introduction Isolated REM sleep behavior disorder (iRBD) is characterized by loss of normal REM sleep atonia and dream enactment behavior. iRBD is strongly associated with α-synucleinopathies and risk for developing Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), yet phenoconversion risk for long-term outcomes of younger women and men remains undefined. We aimed to ascertain longitudinal outcomes and phenoconversion risk in the Mayo Clinic iRBD cohort. Methods Eighty-nine of 165 registry participants with at least one-year follow-up were included. Retrospective chart review attained baseline demographics, age at presentation, baseline Timed Up and Go (TUG) and Montreal Cognitive Assessment (MoCA) scores, and phenoconversion status (iRBD, PD, DLB, mild cognitive impairment [MCI], MSA, or other). Kaplan–Meier survival analysis and Cox proportional hazards modeling were analyzed with alpha at p < 0.05. Results 68 men and 21 women had a mean age of 63 years at polysomnographic diagnosis. At follow-up, 64 (71.9%) remained iRBD; 7 (7.9%) developed PD, 11 (12.4%) developed DLB, 3 (3.4%) developed MCI, 1 (1.1%) developed MSA, and 3 (3.4%) developed another dementia. Abnormal TUG (>12 seconds) occurred in 5.9% and abnormal MoCA (< 24) in 23.3%. Phenoconversion rates were similar in women and men (p = 0.44). Older age at PSG predicted phenoconversion, corresponding to a two-fold increase in risk with each 10-year increase (HR 2.00, 95% CI 1.15–3.52). Neither abnormal TUG nor MoCA predicted conversion. Cumulative phenoconversion was approximately 1% at 1 year, 7% at 3 years, 10% at 5 years, 30% at 10 years, 34% at 12 years, and 49% at 15 years. Mean and median time to phenoconversion was 7 years (range, 1-18 years). Conclusion We found that iRBD phenoconversion rates were lower than historically reported. Only age at presentation predicted phenoconversion, with risk doubling per decade. At 12 years, cumulative phenoconversion rate was approximately 34%. Support (if any)

Abstract Introduction The relationship between sleep and brain metabolism remains unclear. This study aimed to examine whether overnight sleep features, using a home sleep apnea system based on peripheral arterial tonometry, are associated with regional FDG-PET changes in older adults. Methods We analyzed cognitively unimpaired adults (≥60 years) from the Mayo Clinic Study of Aging (MCSA) cohort who were not receiving sleep apnea treatment. Participants underwent overnight sleep assessment with the WatchPAT system, followed by FDG-PET imaging the next morning. FDG-PET data were co-registered to 3T MRI and automatically segmented into 122 anatomical regions. PET signal was referenced to the pons (SUVR). We computed voxel-weighted median FDG signal across 47 bilateral cortical and subcortical regions of interest (ROIs), excluding brainstem and cerebellum. Associations between sleep architecture and sleep apnea/hypoxemia burden and regional metabolism were assessed using partial Spearman’s rank correlation, adjusting for age. Results Thirty-seven participants were included (70.3% female; median [IQR] age: 72.0 [68.0–78.0] years). Wake after sleep onset (WASO) showed widespread negative associations with FDG uptake in cortical regions (p< 0.05), particularly the ventromedial/ventrolateral (rs=–0.47 to –0.33) prefrontal cortex, lateral temporal (rs=–0.38 to –0.33), and occipital (rs=–0.47 to –0.37) cortices. Total sleep time (TST) was positively associated with medial structures (p< 0.05), including the posterior cingulate (rs=0.39), retrosplenial cortex (rs=0.48), hippocampus/parahippocampal (rs=0.34 to 0.36), calcarine cortex (ρ=0.38), thalamus (rs=0.37), and caudate (rs=0.43). Hypoxic burden was positively associated with medial occipital regions (rs=0.35 to 0.39) and AHI-4% with cuneus (rs=0.33). Regional gray matter volume did not mediate these associations. WASO correlated with Insomnia Severity Index (rs=0.43, p=0.008) and self-reported refreshing sleep (rs=0.046). Conclusion Overnight sleep macrostructure features (WASO and TST) and hypoxic burden are significantly associated with brain metabolism, potentially underlying symptoms of sleep disturbance and cognitive aging. Support (if any) Mayo Clinic Alzheimer’s Disease Research Center Development Award (P30 AG062677), R01 AG056366, U01 AG006786, R01 AG056366, R01 AG034676, R37 AG011378, R01 AG041851, R01 NS097495, R01 AG068206, P30 AG062677, R01 HL065176. CLARA project work with funding from the European Union’s HORIZON EUROPE research and innovation programme (No 101136607).