Cesarone, Olivia

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 REM sleep without atonia (RSWA) is the neurophysiological substrate of REM sleep behavior disorder (RBD), a form of prodromal parkinsonism in most older adults. Isolated RSWA (without clinical RBD) elevation was demonstrated recently in older adults following SARS-CoV2 (COVID-19) infection, but comparison to controls was not reported. We aimed to comparatively analyze RSWA between patients with previous COVID-19 infection and COVID-19 negative controls. Methods 25 patients with previous COVID-19 infection were compared to 25 age-sex matched controls who tested negative for COVID-19 prior to polysomnography. Patients receiving medications known to increase RSWA were excluded. We reviewed medical records to determine clinical features and quantitatively analyzed RSWA in the submentalis (SM) and anterior tibialis (AT) muscles for phasic, tonic, and “any” muscle activity, phasic burst duration, and the automated REM atonia index. Non-parametric analyses compared clinical and polysomnographic features between groups, with combined SM and AT RSWA as the defined primary outcome. The comparative frequency of COVID-19 positive cases and COVID-19 negative controls who met or exceeded proposed isolated RSWA thresholds was also determined. Results COVID-19 patients had significantly greater RSWA than COVID-19 negative controls in the combined SM and AT muscles (p = 0.00076). Most other RSWA metrics were also higher in COVID-19 patients than controls (p<0.03), except tonic muscle activity, phasic burst durations, and RAI. Isolated RSWA occurred more frequently in COVID-19 (9 patients, 36%) than controls (3, 12%; p>0.05). No patients had a clinical history or polysomnographic evidence for parasomnia behavior or a primary neurological condition. Conclusion Quantitative RSWA amounts were comparatively greater in COVID-19 patients than in COVID-19 tested-negative controls, suggesting association of previous COVID-19 infection with central nervous system brainstem dysfunction in the region of the dorsal pons and/or ventromedial medulla. Further prospective studies are needed to determine whether RSWA is a predisposing influence to, or consequence of, COVID-19 infection in these patients, and whether COVID-19 survivors might harbor neurodegenerative risk or disease markers. Support (If Any)