Rest-activity Pattern Alterations in Idiopathic REM Sleep Behavior Disorder.

OBJECTIVE To investigate the differences in actigraphy-measured rest-activity patterns (e.g., sleep-wake cycle, circadian rest-activity rhythm, and physical activity) across different stages of α-synucleinopathy. METHODS We compared alterations in 7-day actigraphy-measured rest-activity patterns among patients with clinically diagnosed α-synucleinopathies (n = 44), and their age-, sex-, and BMI-matched patients with idiopathic REM sleep behavior disorder (iRBD, n = 88), and non-RBD controls (n = 44) in a case-control study (Study 1) and between convertors (n = 22) and their age-, sex-, BMI-, iRBD-duration and follow-up-duration-matched non-convertors (n = 66) in a prospective nested case-control study (Study 2). RESULTS In Study 1, there were significantly increases (P values were adjusted by false discovery rate < 0.01) in probable napping behaviors (percentage, duration, and episodes), activity fragmentation (estimated by kAR ), and physical inactivity during active period across controls, iRBD, to clinically diagnosed α-synucleinopathies. In Study 2, higher levels (all P values were adjusted by false discovery rate < 0.05) of baseline objective probable napping, activity fragmentation, and physical inactivity during active period were associated with the conversion of iRBD patients into clinically diagnosed α-synucleinopathies at two years of follow-up with medium to large effect sizes (Cohen's d: 0.56 to 0.80). These findings were further supported by functional linear modeling analyses. INTERPRETATION Rest-activity pattern alterations, mainly objective probable napping behaviors, activity fragmentation, and physical inactivity during active period, emerge as early as at the stage of iRBD, which serve as early and robust prodromal markers of the conversion of iRBD into clinically diagnosed α-synucleinopathies. This article is protected by copyright. All rights reserved.