Risk Factors for Phenoconversion in Rapid Eye Movement Sleep Behavior Disorder.

OBJECTIVE: This study was undertaken to follow up predictive factors for α-synuclein-related neurodegenerative diseases in a multicenter cohort of idiopathic/isolated rapid eye movement sleep behavior disorder (iRBD). METHODS: Patients with iRBD from 12 centers underwent a detailed assessment for potential environmental and lifestyle risk factors via a standardized questionnaire at baseline. Patients were then prospectively followed and received assessments for parkinsonism or dementia during follow-up. The cumulative incidence of parkinsonism or dementia was estimated with competing risk analysis. Cox regression analyses were used to evaluate the predictive value of environmental/lifestyle factors over a follow-up period of 11 years, adjusting for age, sex, and center. RESULTS: Of 319 patients who were free of parkinsonism or dementia, 281 provided follow-up information. After a mean follow-up of 5.8 years, 130 (46.3%) patients developed neurodegenerative disease. The overall phenoconversion rate was 24.2% after 3 years, 44.8% after 6 years, and 67.5% after 10 years. Patients with older age (adjusted hazard ratio [aHR] = 1.05) and nitrate derivative use (aHR = 2.18) were more likely to phenoconvert, whereas prior pesticide exposure (aHR = 0.21-0.64), rural living (aHR = 0.53), lipid-lowering medication use (aHR = 0.59), and respiratory medication use (aHR = 0.36) were associated with lower phenoconversion risk. Risk factors for those converting to primary dementia and parkinsonism were generally similar, with dementia-first converters having lower coffee intake and beta-blocker intake, and higher occurrence of family history of dementia. INTERPRETATION: Our findings elucidate the predictive values of environmental factors and comorbid conditions in identifying RBD patients at higher risk of phenoconversion. ANN NEUROL 2022;91:404-416.

Diagnosing REM sleep behavior disorder in Parkinson's disease without a gold standard: a latent-class model study.

STUDY OBJECTIVES: To ascertain whether current diagnostic criteria for REM sleep behavior disorder (RBD) are appropriate in patients with Parkinson's disease (PD) consulting a movement disorder center, to evaluate the accuracy of REM sleep without atonia (RSWA) thresholds and determine the value of screening questionnaires to discriminate PD patients with RBD. METHODS: One hundred twenty-eight consecutive PD patients (M = 80; mean age: 65.6 ± 8.3 years) underwent screening questionnaires, followed by a sleep-focused interview and a full-night video-polysomnography (vPSG). Without a gold standard, latent class models (LCMs) were applied to create an unobserved ("latent") variable. Sensitivity analysis was performed using RSWA cutoff derived from two visual scoring methods. Finally, we assessed the respective diagnostic performance of each diagnostic criterion for RBD and of the screening questionnaires. RESULTS: According to the best LCM-derived model, patients having either "history" or "video" with RSWA or alternatively showing both "history" and "video" without RSWA were classified as having RBD. Using both SINBAR and Montreal scoring methods, RSWA criterion showed the highest sensitivity while concomitant history of RBD and vPSG-documented behaviors, regardless to presence of RSWA, displayed the highest specificity. Currently recommended diagnostic threshold of RSWA was found to be optimal in our large cohort of PD patients. Both the RBD screening questionnaire (RBDSQ) and the RBD single question (RBD1Q) showed poor sensitivity and specificity. CONCLUSIONS: Results of the best LCM for diagnosis of RBD in PD were consistent with the current diagnostic criteria. Moreover, RBD might be considered in those PD patients with both history and vPSG-documented dream enactment behaviors, but with RSWA values within the normal range.

Sleep cardiac dysautonomia and EEG oscillations in amyotrophic lateral sclerosis.

STUDY OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease due to loss of motor neurons. However, the autonomic nervous system (ANS) can also be involved. The aim of this research was to assess the sleep macro- and microstructure, the cardiac ANS during sleep, and the relationships between sleep, autonomic features, and clinical parameters in a cohort of ALS patients. METHODS: Forty-two consecutive ALS patients underwent clinical evaluation and full-night video-polysomnography. Only 31 patients met inclusion criteria (absence of comorbidities, intake of cardioactive drugs, or recording artifacts) and were selected for assessment of sleep parameters, including cyclic alternating pattern (CAP) and heart rate variability (HRV). Subjective sleep quality and daytime vigilance were also assessed using specific questionnaires. RESULTS: Although sleep was subjectively perceived as satisfactory, compared with age- and sex-matched healthy controls, ALS patients showed significant sleep alteration: decreased total sleep time and sleep efficiency, increased nocturnal awakenings, inverted stage 1 (N1)/stage 3 (N3) ratio, reduced REM sleep, and decreased CAP rate, the latter supported by lower amounts of A phases with an inverted A1/A3 ratio. Moreover, a significant reduction in HRV parameters was observed during all sleep stages, indicative of impaired autonomic oscillations. CONCLUSION: Our results indicate that sleep is significantly disrupted in ALS patients despite its subjective perception. Moreover, electroencephalogram activity and autonomic functions are less reactive, as shown by a decreased CAP rate and a reduction in HRV features, reflecting an unbalanced autonomic modulation.

Comorbidity and medication in REM sleep behavior disorder: a multicenter case-control study.

OBJECTIVE: This controlled study investigated associations between comorbidity and medication in patients with polysomnographically confirmed idiopathic REM sleep behavior disorder (iRBD), using a large multicenter clinic-based cohort. METHODS: Data of a self-administered questionnaire on comorbidity and medication use of 318 patients with iRBD and 318 matched controls were analyzed. Comparisons between cases and controls were made using logistic regression analysis. RESULTS: Patients with iRBD were more likely to report depression (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.3-2.9) and concomitant antidepressant use (OR 2.2, 95% CI 1.4-3.6). Subanalysis of antidepressant agents revealed that the increased use of antidepressants in iRBD was due to selective serotoninergic reuptake inhibitors (OR 3.6, 95% CI 1.8-7.0) and not due to other antidepressant classes. Patients with iRBD reported more lifetime antidepressant use than comorbid depression (antidepressant use: OR 1.9, 95% CI 1.1-3.3; depression: OR 1.6, 95% CI 1.0-2.5). Patients with iRBD reported more ischemic heart disease (OR 1.9, 95% CI 1.1-3.1). This association did not change substantially when adjusting for cardiovascular risk factors (OR 2.3, 95% CI 1.3-3.9). The use of inhaled glucocorticoids was higher in patients with iRBD compared to controls (OR 5.3, 95% CI 1.8-15.8), likely reflecting the higher smoking rate in iRBD (smoking: OR 15.3, 95% CI 2.0-118.8; nonsmoking: OR 2.4, 95% CI 0.4-13.2) and consequent pulmonary disease. CONCLUSIONS: This large study confirms the association between comorbid depression and antidepressant use in iRBD. In addition, there was an unexpected association of iRBD with ischemic heart disease that was not explained by cardiovascular risk factors.