Timeline of Rapid Eye Movement Sleep Behavior Disorder in Overt Alpha‐Synucleinopathies
Open accessAbstract
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
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Biological mechanisms include neuroinflammation, atherosclerosis, alpha-synucleinopathies, and impaired amyloidβ clearance.
“Biological mechanisms include neuroinflammation,(312) atherosclerosis,(313) alpha-synucleinopathies (dementia with Lewy bodies and Parkinson disease dementia),(314) and impaired amyloidβ clearance. (315)”
From Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission (2024) · cites this paper as [314]
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“최근 보 고된 코호트 연구에 따르면 시누클레인병으로 확진된 444명의 환 자와 444명의 대조군을 후향적으로 비교하였을 때, 시누클레인병 을 가진 환자에서 대조군에 비해 RBD 발생률(incidence)이 53배 더 많았다.(37) 처음 진단되는 시점에서 RBD 환자는 건강한 상태이”
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Malkani, R. G., & Avidan, A. Y. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-822963-7.00340-6 · Cited by 1 · see citing works
The Role of Melatonin and Disrupted Sleep in Neurologic Disorders
Hurley, D. (2021) · Neurology Today · doi:10.1097/01.nt.0000756444.61541.74
Autonomic dysfunction during sleep in Parkinson's disease
Baschieri, F., Guaraldi, P., Cortelli, P., & Buonaura, G. C. (2021) · International review of movement disorders · doi:10.1016/bs.irmvd.2021.07.005
Epidemiology and risk factors for parasomnias in children and adults
Grigg-Damberger, M. M., Foldvary‐Schaefer, N., & Wolfe, K. M. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-822963-7.00334-0
Reading the mind in the eyes in patients with idiopathic REM sleep behavior disorder
Li, X., Shen, M., Shen, Z., Han, Z., Jiao, J., & Tong, X. (2024) · Neurological Sciences · doi:10.1007/s10072-024-07303-3
“The risk of phenoconversion from iRBD to an overt ɑ -synucleinopathy is approximately 7 to 8% per year, approaching 35% at 5 years and between 41 and 91% risk following 6 to 15 years [3].”
InfluentialBaumgartner, A. J., & Amara, A. W. (2025) · SLEEP · doi:10.1093/sleep/zsaf203
Branson, C. O. (2026) · CONTINUUM Lifelong Learning in Neurology · doi:10.1212/cont.0000000000001734
- Authors
- Stang, C. D., Mullan, A. F., Hajeb, M., Camerucci, E., Turcano, P., Martin, P., Mielke, M. M., Josephs, K. A., Bower, J. H., St Louis, E. K., Boeve, B. F., & Savica, R.
- Affiliations
- Mayo Clinic (US)
- Department of Neurology Mayo Clinic Rochester MN USA
- Corresponding author
- Savica, Rodolfo
- ORCID
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2020-11-20
- Volume
- 89
- Issue
- 2
- Pages
- 293-303
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC8080353
- OpenAlex
- W3095559746
- Cited by
- 29
- References
- 45
- Citations by year
- 2026: 1 · 2025: 11 · 2024: 6 · 2023: 3 · 2022: 4 · 2021: 4
- FWCI
- 1.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Center for Advancing Translational Sciences (UL1 TR002377)
- National Institute on Aging (R01 AG034676)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- rapid eye movement sleep behavior disorder, synucleinopathies, Parkinson's disease, dementia with Lewy bodies, Parkinson's disease dementia, sex differences, dream enactment, Lewy bodies, REM sleep
- MeSH terms
- Synucleinopathies, Aged, Aged, 80 and over, Female, Humans, Male, Mortality, Parkinson Disease, Incidence, Prevalence, Case-Control Studies, Polysomnography, Sex Distribution, Disease Progression, REM Sleep Behavior Disorder, Lewy Body Disease
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