Ambulatory detection of isolated REM sleep behavior disorder combining actigraphy and questionnaire

Background Isolated rapid-eye-movement sleep behavior disorder (iRBD) is in most cases a prodrome of neurodegenerative synucleinopathies, affecting 1-2% of middle-aged and older adults, however accurate ambulatory diagnostic methods are lacking. Questionnaires lack specificity in non-clinic populations. Wrist actigraphy can detect characteristic features in individuals with RBD, however high frequency actigraphy has rarely been used. Objectives To develop a machine learning classifier using high frequency (1-second resolution) actigraphy and a short patient survey for detecting iRBD with high accuracy and precision. Methods Analysis of ≥7 nights home actigraphy data and 9-item questionnaire (RBD Innsbruck inventory and 3 synucleinopathy prodromes of subjective hyposmia, constipation and orthostatic dizziness) in a dataset including 42 patients with iRBD, 21 sleep clinic patients with other sleep disorders, and 21 community controls. Results The actigraphy classifier achieved 95.2% (95% CI: 88.3 - 98.7) sensitivity and 90.9% (95% CI: 82.1 - 95.8) precision. The questionnaire classifier achieved 90.6% accuracy and 92.7% precision, exceeding performance of RBD-I and prodromal questionnaire alone. Concordant predictions between actigraphy and questionnaire reached specificity and precision of 100% (95% CI: 95.7 - 100.0) with 88.1% sensitivity (95% CI: 79.2 - 94.1) and outperformed any combination of actigraphy plus single question on RBD or prodromal symptoms. Conclusions Actigraphy detected iRBD with high accuracy in a mixed clinical and community cohort. This cost-effective fully remote procedure can be used to diagnose iRBD in specialty outpatient settings and has potential for large scale screening of iRBD in the general population. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by Feldman Foundation CA. Additional support to Andreas Brink-Kjaer was provided by the Stibo, Oberstloejtnant Max Noergaard % Hustru Magda Noergaards, Otto Moensted, Augustinus, Knud Hoejgaard, William Demant, Vera % Carl Johan Michaelsens, Tranes, Marie % M.B. Richters Fond, and IDAs % Berg-Nielsens foundations. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Institutional Review Board of Stanford and all participants provided written informed consent. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors-