Early- and Late-onset of Isolated Rapid Eye Movement Sleep Behavior Disorder: A Retrospective Cohort Study

Objective: Age at onset of neurodegenerative disease has significant implications in differentiating disease profiles. We aimed to determine whether age at onset could identify clinical and neurodegenerative profiles in patients with isolated/idiopathic rapid eye movement sleep behavior disorder (iRBD) - a prodromal stage of α-synucleinopathies.

Methods: In this retrospective cohort study, the time of the first episode of dream-enactment behaviors that the patient/bed-partners recalled at the time of the patient's first visit to sleep clinic was collected. The distribution of age at onset was examined and patients were dichotomized into early- and late-onset groups based on the intersection point of underlying two Gaussian distributions of onset age.

Results: A total of 241 patients were included. The intersection of underlying two Gaussian models of onset age was 64.6 years, yielding 168 early- (median onset age: 58.0 years, range: 38.0-64.0) and 73 late-onset patients (median onset age: 70.0 years, range: 65.0-82.0). Among them, 154 of early- and 68 late-onset patients were followed-up. Late-onset patients had milder RBD symptoms, but worse sleep, cognition, olfactory and motor functions, and a higher risk of phenoconversion (adjusted hazard ratio (aHR) = 2.2, 95% confidence interval (CI) = 1.2-3.9), especially to probable dementia with Lewy bodies (DLB) (aHR = 8.9, 95% CI = 3.0-26.2), than early-onset patients.

Conclusions: Late-onset iRBD was associated with a higher level of neurodegenerative markers and a quicker phenoconversion, especially to probable DLB. Age at onset of iRBD could help identify clinical features and predict prognosis of iRBD.