Timeline of Rapid Eye Movement Sleep Behavior Disorder in Overt Alpha-Synucleinopathies

Abstract

Objective: The aim was to analyze the timeline, prevalence, and survival of rapid eye movement (REM) sleep behavior disorder (RBD) in patients who developed alpha-synucleinopathies (Parkinson disease, dementia with Lewy bodies, and Parkinson disease dementia) compared with age- and sex-matched controls in a population-based incident-cohort study.

Methods: We used a population-based, 1991 to 2010 incident-cohort study of alpha-synucleinopathies. A movement-disorder specialist reviewed medical records to confirm diagnoses. RBD was diagnosed by reported dream-enactment symptoms or polysomnography. Probable RBD and polysomnographically confirmed RBD were analyzed separately and combined.

Results: Among the 444 incident cases of alpha-synucleinopathy, 86 were clinically diagnosed with RBD (19.8%), including 30 (35%) by polysomnography and 56 (65%) as probable. The prevalence of idiopathic RBD at alpha-synucleinopathy diagnosis was 3.4%, increasing to 23.8% after 15 years. Cumulative lifetime incidence was 53 times greater in alpha-synucleinopathy patients than in controls (odds ratio [OR] = 53.1, 95% confidence interval [CI]: 13.0-217.2, p < 0.0001), higher in dementia with Lewy bodies than in Parkinson disease (OR = 2.57, 95% CI: 1.50-4.40, p = 0.0004), and higher in men than in women with Parkinson disease, dementia with Lewy bodies, or Parkinson disease dementia (OR = 3.70, 95% CI: 2.07-6.62, p < 0.0001), but did not increase mortality risk.

Interpretation: Our cohort had RBD incidence of 3.4%. Overall RBD increased to 23.8% after 15 years, with an overall incidence of 2.5 cases per 100 person-years. With 53 times greater lifetime incidence in alpha-synucleinopathy patients than in controls, RBD was more likely to develop in dementia with Lewy bodies than in Parkinson disease or Parkinson disease dementia, and in men than in women, but did not increase mortality risk within our cohort. ANN NEUROL 2021;89:293-303.

Figure 1:

The incident rate of RBD cases is reported for each diagnostic subtype of overt alpha-synucleinopathy and controls in five-year increments.

Figure 2:

RBD prevalence is reported for each individual overt alpha-synucleinopathy in five disease year increments. The diagnosis of overt alpha-synucleinopathy is indicated by time 0 on the x-axis. The bottom table within Figure 2 reports the individual RBD events per 5-year increments either before or after the onset of overt alpha-synucleinopathy.

Figure 3:

The median lifelong timeline of RBD progression is represented in each overt alpha-synucleinopathy subtype (yellow=control, blue=PD, green=DLB, purple=PDD). The x-axis represents the years before and after the onset of overt alpha-synucleinopathy (onset is indicated by the number 0). The timeline of the progression of RBD is represented by the horizontal lines. The circle represents the median onset of RBD symptoms. The transparent line indicates the median latency from RBD symptom onset to diagnosis. The solid line indicates the median time from RBD diagnosis to the date of last follow-up or death.

Figure 4:

The life-long timeline of RBD development is shown in each individual patient differentiated by disease subtype (yellow=control, blue=PD, green=DLB, purple=PDD). The x-axis represents the years before and after the onset of parkinsonism (onset is indicated by the number 0). For each subtype of alpha-synucleinopathy, the timeline of the development of RBD is represented by the horizontal lines. The circle represents each individual’s onset of RBD symptoms. The transparent line indicates each individual’s latency from RBD symptom onset to diagnosis. The solid line indicates each individual’s time from RBD diagnosis to the date of last follow-up or death.