Shprecher, David

Abstract Objective Rapid eye movement (REM) sleep behavior disorder (RBD) is widely considered a prodromal synucleinopathy, as most with RBD develop overt synucleinopathy within ~10 years. Accordingly, RBD offers an opportunity to test potential treatments at the earliest stages of synucleinopathy. The North American Prodromal Synucleinopathy (NAPS) Consortium has created a multisite RBD participant, primarily clinic‐based cohort to better understand characteristics at diagnosis, and in future work, identify predictors of phenoconversion, develop synucleinopathy biomarkers, and enable early stage clinical trial enrollment. Methods Participants ≥18 years of age with overnight polysomnogram‐confirmed RBD without Parkinson's disease, dementia, multiple system atrophy, or narcolepsy were enrolled from nine sites across North America (8/2018 to 4/2021). Data collection included family/personal history of RBD and standardized assessments of cognitive, motor, sensory, and autonomic function. Results Outcomes are primarily reported based on sex (361 total: n = 295 male, n = 66 female), and secondarily based on history of antidepressant use ( n = 200 with, n = 154 without; with correction for sex differences) and based on extent of synucleinopathy burden ( n = 56 defined as isolated RBD, n = 305 defined as RBD+ [i.e., exhibiting ≥1 abnormality]). Overall, these participants commonly demonstrated abnormalities in global cognition (MoCA; 38%), motor function (alternate tap test; 48%), sensory (BSIT; 57%), autonomic function (orthostatic hypotension, 38.8%), and anxiety/depression (BAI and PHQ‐9; 39.3% and 31%, respectively). Interpretation These RBD participants, assessed with extensive history, demographic, cognitive, motor, sensory, and autonomic function demonstrated a lack of sex differences and high frequency of concomitant neurological abnormalities. These participants will be valuable for future longitudinal study and neuroprotective clinical trials.

Abstract This study was designed to correlate clinical findings with the extent of pathologic a-synuclein (aSyn) in the brain using the Unified Staging System for Lewy Body disorders (USSLB). Data from 280 cases from the Arizona Study of Aging and Neurodegenerative Disorders are presented. Each case had a complete USSLB staging and at least 1 full research clinical assessment, including subspecialty neurologist-administered movement and cognitive evaluation. Of the 280, 25.7% were cognitively normal, 8.6% had mild cognitive impairment, and 65.7% had dementia. All cases could be categorized into 1 of 5 USSLB stages (8.6% stage I—olfactory bulb only; 15.4% IIa—brainstem predominant; 13.6% IIb—limbic predominant; 31.8% III—brainstem and limbic; and 30.7% IV—neocortical) yet using the Braak staging system 70 cases (25.3%) could not be classified. Those with USSLB stages III and IV died at a younger age. Multiple measures of motor parkinsonism, cognitive impairment, hyposmia, and probable RBD were significantly correlated with increasing USSLB stage. We conclude that the USSLB is the most comprehensive staging system for all Lewy body disorders and allows for categorization and ranking of all brains with significant correlations to many motor and nonmotor clinical signs and symptoms.

Background: The prevalence of dream enactment behavior and other risk factors for a parkinsonian disorder is not well documented. Methods: A survey on prevalence of parkinsonism risk factors was designed using two validated instruments (REM behavior disorder single item question, bowel movement frequency for constipation) and three exploratory instruments (for hallucinations, cognitive and olfactory complaints.) It was sent by mail and email to patients aged 50 and over at two University of Utah community clinics in Salt Lake City. A total of 7888 unique patients were sent the survey, and 1607 responses were recorded (response rate 20%). Those whose age was missing (n = 117) or less than 50 years (n = 10) were excluded from the analysis. Results: Of the 1406 without personal diagnosis of neurodegenerative disease 62.7% were female, and median age was 63. Family history (FH) of Parkinson’s disease was endorsed by 9%, constipation (defined as a bowel movement less than once per day) by 19%, mild cognitive complaints (MCI) 15.8%, dream enactment 13.7%, subjective hyposmia or anosmia 18.2%, and at least one potential psychotic symptom in 37.6%. Multivariable logistic regression showed male gender, mild cognitive complaints, hearing voices, and at least one potentially psychotic symptom to be significantly associated with dream enactment. Conclusions: This survey shows that dream enactment, a strong predictor of risk for synucleinopathy, is relatively common in the older population; because such individuals rarely come to medical attention of a sleep clinic, such survey research may be useful to identify and recruit at-risk individuals for trials aimed at preventing neurodegenerative disease.