Teigen, Luke

ObjectiveThis study assessed the relationship between speech and language impairment and outcome in a multicenter cohort of isolated/idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD).MethodsPatients with iRBD from 7 centers speaking Czech, English, German, French, and Italian languages underwent a detailed speech assessment at baseline. Story‐tale narratives were transcribed and linguistically annotated using fully automated methods based on automatic speech recognition and natural language processing algorithms, leading to the 3 distinctive linguistic and 2 acoustic patterns of language deterioration and associated composite indexes of their overall severity. Patients were then prospectively followed and received assessments for parkinsonism or dementia during follow‐up. The Cox proportional hazard was performed to evaluate the predictive value of language patterns for phenoconversion over a follow‐up period of 5 years.ResultsOf 180 patients free of parkinsonism or dementia, 156 provided follow‐up information. After a mean follow‐up of 2.7 years, 42 (26.9%) patients developed neurodegenerative disease. Patients with higher severity of linguistic abnormalities (hazard ratio [HR = 2.35]) and acoustic abnormalities (HR = 1.92) were more likely to develop a defined neurodegenerative disease, with converters having lower content richness (HR = 1.74), slower articulation rate (HR = 1.58), and prolonged pauses (HR = 1.46). Dementia‐first (n = 16) and parkinsonism‐first with mild cognitive impairment (n = 9) converters had higher severity of linguistic abnormalities than parkinsonism‐first with normal cognition converters (n = 17).InterpretationAutomated language analysis might provide a predictor of phenoconversion from iRBD into synucleinopathy subtypes with cognitive impairment, and thus can be used to stratify patients for neuroprotective trials. ANN NEUROL 2024;95:530–543

Abstract Study Objectives Isolated REM sleep behavior disorder (iRBD) carries a high lifetime risk for phenoconversion to a defined neurodegenerative disease (NDD) including Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. We aimed to examine iRBD patient values and preferences regarding prognostic counseling. Methods One hundred thirteen iRBD patient participants enrolled in the Mayo Clinic iRBD Patient Registry were sent an email survey concerning their values and preferences concerning NDD prognostic counseling and their experiences following diagnosis with iRBD. Results Of 81 respondents (71.7% response rate), the majority were men (74.0%) with an average age of 65.7 (±9.7) years. Responses indicated a strong preference toward receiving prognostic information about possible future NDD development. 92.5% of respondents felt knowledge concerning personal NDD risk was important, while 87.6% indicated prognostic discussions were important to maintaining trust in their physician. 95.7% indicated a desire for more information, while only 4.3% desired less information regarding their NDD prognostic risk. Most respondents strongly agreed that prognostic information was important to discuss with their family and friends and inform future life planning, and most expressed interest in learning more about future neuroprotective therapies and symptomatic treatments for parkinsonism and dementia. Conclusions Most iRBD patients indicated strong preferences for disclosure of NDD prognostic risk and indicated that prognostic information was important for family discussions and future life planning. Future broader surveys and qualitative studies of clinic-based and ultimately community dwelling iRBD patients’ values and preferences are needed to guide appropriately tailored and individualized prognostic counseling approaches following iRBD diagnosis.

AbstractBackgroundTo examine patient preferences regarding prognostic counseling for idiopathic/isolated REM sleep behavior disorder (iRBD). Idiopathic/isolated REM sleep behavior disorder (iRBD) carries an approximate 73‐91% long term risk for phenoconversion to dementia with Lewy bodies (DLB) and Parkinson disease (PD). Previous research has shown that most providers counsel their patients concerning this risk, yet patients’ values and preferences regarding counseling are unknown.Methods122 participants with iRBD in the Mayo Clinic iRBD Patient Registry enrolled. Participants were sent a survey concerning prognostic counseling and their experience in being diagnosed with iRBD.ResultsOf 81 respondents (67.2% response rate), 74% were men with an average age of 65.7 ± 9.7 years. Responses indicated a strong preference toward receiving prognostic information; 92.5% felt knowledge concerning neurodegenerative disease risk was important, while 87.6% felt prognostic discussion was important to maintain trust in their physician. Additionally, 95.7% indicated they desired more information, while only 4.3% would have desired less information regarding prognostic risk following iRBD diagnosis. Most respondents agreed strongly that prognostic information was important for discussions with their family and friends and future life planning, and expressed interest in learning more about future neuroprotective therapies and symptomatic treatments for parkinsonism and dementia.ConclusionsiRBD patients indicated a strong preference for disclosure of neurodegenerative prognostic risk information, preferred more rather than less information, and felt prognostic information was important for family discussions and life planning. This data informs prognostic counseling practices regarding iRBD and other neurodegenerative diseases.

Abstract Study Objectives Post-traumatic stress disorder (PTSD) and rapid eye movement (REM) sleep behavior disorder (RBD) share some common features including prominent nightmares and sleep disturbances. We aimed to comparatively analyze REM sleep without atonia (RSWA) between patients with chronic PTSD with and without dream enactment behavior (DEB), isolated RBD (iRBD), and controls. Methods In this retrospective study, we comparatively analyzed 18 PTSD with DEB (PTSD+DEB), 18 PTSD without DEB, 15 iRBD, and 51 controls matched for age and sex. We reviewed medical records to determine PTSD clinical features and quantitatively analyzed RSWA. We used nonparametric analyses to compare clinical and polysomnographic features. Results PTSD patients, both with and without DEB, had significantly higher RSWA than controls (all p < .025, excepting submentalis phasic duration in PTSD+DEB). Most RSWA measures were also higher in PTSD+DEB than in PTSD without DEB patients (all p < .025). Conclusions PTSD patients have higher RSWA than controls, whether DEB is present or not, indicating that REM sleep atonia control is abnormal in chronic PTSD. Further prospective studies are needed to determine whether neurodegenerative risk and disease markers similar to RBD might occur in PTSD patients.

Abstract Introduction REM sleep behavior disorder (RBD) is characterized by disruptive, violent dream enactment behaviors (DEB), necessitating symptomatic treatment to prevent injury and reduce DEB frequency and severity. Melatonin and clonazepam are regarded as RBD therapeutic mainstays, although outcomes data remains limited. We surveyed RBD patients to determine their outcomes following melatonin, clonazepam, and melatonin-clonazepam combination therapy. Methods Mayo Clinic RBD Patient Registry participants received an electronic survey concerning treatment type(s) and dose(s), efficacy, and adverse effects. The primary outcome was treatment efficacy, determined by comparing DEB frequency/severity ratings on a visual analog scale (VAS). Adverse effects severity was assessed by Likert scales. We comparatively analyzed VAS before and after treatment and adverse effects between treatments using non-parametric statistical tests. Results Sixty-eight of 109 patients responded (62.3%; 64 had analyzable data) with a mean age of 67.7 years. Fifty-seven (85%) were men, with mean RBD symptom duration of 13.9 years. Patients receiving each treatment were: melatonin=30, clonazepam=8, and combination=12; 14 received other or no treatment. Baseline VAS ratings were similar between groups. Only melatonin (p=0.003) and combination therapy (p=0.039) improved VAS ratings; clonazepam monotherapy did not improve VAS. Only melatonin monotherapy was reported to lower VAS compared to untreated patients (p=0.02). Optimally effective mean dosages were melatonin 9.95±5.06 mg and clonazepam 0.81±0.48 mg. Patient frequencies reporting one or more moderately-severe side effect(s) were similar between melatonin (15%), clonazepam (7%), and combination therapies (9%). Twenty-five (36.8%) patients had received only one medication trial, while 41.2% required more than one medication. Of these, 15 (22.1%) tried 2 and 13 (19.1%) tried 3 or more treatments. Conclusion Melatonin therapy at an approximate mean 10 mg dosage improved patient-reported DEB frequency/severity on VAS, compared between both previous intraindividual baseline ratings and with untreated patients, while clonazepam monotherapy did not, without differential adverse effects. Clonazepam monotherapy data were limited. These data inform future prospective melatonin symptomatic therapy trials for RBD. Additionally, 41.2% required more than one RBD pharmacological treatment, suggesting a current therapeutic gap and unmet need for future development of biologically-informed, evidence-based symptomatic RBD therapeutics. Support (if any):