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This study aimed to establish the diagnostic accuracy of a previously validated sleep staging system in patients with probable isolated REM sleep behavior disorder (iRBD), and to compare physicians' diagnoses of iRBD based on REM sleep without atonia (RSWA) to non-REM hypertonia (NRH), a sleep measure independently associated with Parkinsonian spectrum disorders. Twenty-six patients with a history of dream enactment behavior underwent a diagnostic PSG with simultaneous Sleep Profiler (SP) acquisition at two sites. PSG and SP records were sleep staged, and two sleep neurologists independently diagnosed iRBD based on the presence or absence of polysomnographic identified RSWA. Comparisons for PSG vs SP sleep staging and the qualitative presence or absence of PSG-based RSWA vs automated SP-detected NRH was performed using kappa coefficients ( ), positive and negative percent agreements (PPA and NPA), and chi-square tests. The kappa scores from Sites-1 and -2 for PSG vs SP staging were different for Wake ( =0.82 vs 0.65), N2 ( =0.63 vs 0.72) and REM ( =0.83 vs.0.72). The by-site kappa values for stage N3 increased from 0.72 and 0.37 to 0.88 and 0.74 after PSG records were reedited. The kappa values for between-physician agreement in iRBD diagnoses were fair (k = 0.22). The agreement between each physician's iRBD diagnoses and NRH were also fair ( =0.29 and 0.22). Abnormal NRH agreed with at least one physician's iRBD diagnosis in 83% of the records. The PPA resulting from between-physician iRBD agreement was stronger and the NPA weaker than the values obtained from comparison of each physician's iRBD diagnosis and abnormal NRH. The potential utility of RSWA and stage N3 as neurodegenerative disorder biomarkers was influenced by between-site variability in visual scoring. The degree to which NRH was associated with iRBD was similar to the between-physician agreement in their diagnosis of iRBD using RSWA.

Abstract Introduction: The majority of patients with idiopathic REM sleep behavior disorder (iRBD) are thought to have prodromal synucleinopathy. 25–60% of iRBD patients have probable neurodegenerative biomarkers such as olfactory, orthostatic blood pressure, cognitive, or motor function impairments. We aimed to describe frequencies of neurodegenerative biomarkers in the Mayo Clinic iRBD prospective registry cohort. Methods: We included adults diagnosed with iRBD by ICSD-3 criteria, and excluded symptomatic RBD patients (i.e., diagnosis of mild cognitive impairment, dementia with Lewy bodies, Parkinson disease, or multiple system atrophy). We considered clinical neurodegenerative biomarker measures as abnormal when subjects met age-gender defined cut-offs for the brief Smell Identification Test (BSIT) and neurocognitive assessments (Montreal Cognitive Assessment (MOCA), “Kokmen” Short Test of Mental Status (STMS) and King-Devick Test (KDT)), orthostatic systolic blood pressure (SBP) drop >10 mm Hg, or timed up and go (TUG) speed > 7.5 seconds. Results: 38 iRBD subjects participated. Mean age was 65.4 (range 21 - 84) years, and 12 (31%) were women. Duration of dream enactment was 11+/-16 years. 18 (47%) were receiving antidepressant medications. Mean (range) measure scores were: BSIT 8.8 (4–12); MOCA, 26.2 (20–30); STMS, 34.3 (30–38); KD, 60.2 (39–125.6); SBP drop, 14.64 (1–49); and TUG, 8.5 (5.3–13.8) seconds. The number (%) with abnormal biomarker measures were: BSIT, 6 (16%); MoCA, 6 (16%); STMS, 0%; KD, 12 (32%); SBP drop, 15 (41%); and TUG, 11 (31%). Overall, 31 (82%) had one or more clinical neurodegenerative biomarkers at baseline, and 20 (52%) had two or more biomarkers at baseline. Antidepressant medication was not associated with abnormality on any of the measures. Conclusion: 82% of iRBD patients had at least one neurodegenerative biomarker present, suggesting that iRBD is a prodromal synucleinopathy. Further longitudinal analyses of this cohort compared to age-gender matched control subjects is planned. Support (If Any): Mayo Clinic CCaTS.

Abstract Introduction: Idiopathic REM sleep behavior disorder (iRBD) is highly associated with neurodegenerative diseases, especially the synucleinopathies, in adults over age 50 years. Several previous studies have examined the strong association between RBD and synucleinopathies in predominantly male patient populations, but relatively little is known about the clinical course of RBD in women, and the longitudinal influence of antidepressant use on development of a defined neurodegenenerative disease. We aimed to analyze the rate of phenoconversion from iRBD to a defined neurodegenerative disorder, including Parkinson disease, mild cognitive impairment, dementia with Lewy bodies, and multiple system atrophy in women with and without antidepressant use. Methods: We retrospectively reviewed 77 women with iRBD seen at Mayo Clinic between 1990 and 2016. The Kaplan-Meier method was used to estimate the time of disease-free survival between iRBD symptom onset and phenoconversion to a defined neurodegenerative disease, and to assess associated clinical factors for disease progression. Results: Phenoconversion to a defined neurodegenerative disease was 22.5% at 5 years, 43.2% at 10 years, 66.6% at 15 years, and 91.5% at 21.7 years. Median follow-up duration after symptom onset was 11.7 years (95%ile range 8–17.7 years), median age of RBD onset was 54.5 years, and median age of neurodegenerative disease development was 64 years. 23% of women had a non-REM overlap parasomnia, and 70.5% were taking antidepressants. Antidepressant users had a median disease-free survival of 16.5 years, compared to 8.9 years for antidepressant non-users (p=0.06). Conclusion: The risk of phenoconversion to a defined neurodegenerative disorder in women with iRBD is comparably high to previous male predominant cohorts over longitudinal followup from RBD symptom onset, yet appears to be slower than in some prior studies, possibly associated with frequent antidepressant use in our cohort. Further comparative analysis of men with iRBD including both antidepressant users and non-users will be necessary to clarify the impact of gender and antidepressant use on disease-free survival in iRBD. Support (If Any): Mayo Clinic CCaTS.