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Cited by 393Parkinson's Disease Mechanisms and TreatmentsDementia and Cognitive Impairment ResearchSleep and related disorders

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Clinicopathologic correlations in 172 cases of rapid eye movement sleep behavior disorder with or without a coexisting neurologic disorder

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Boeve, B.F., Silber, M.H., Ferman, T.J., Lin, S.C., Benarroch, E.E., Schmeichel, A.M., Ahlskog, J.E., Caselli, R.J., Jacobson, S., Sabbagh, M., Adler, C., Woodruff, B., Beach, T.G., Iranzo, A., Gelpi, E., Santamaria, J., Tolosa, E., Singer, C., Mash, D.C., Luca, C., Arnulf, I., Duyckaerts, C., Schenck, C.H., Mahowald, M.W., Dauvilliers, Y., Graff-Radford, N.R., Wszolek, Z.K., Parisi, J.E., Dugger, B., Murray, M.E., Dickson, D.W.·2013·Sleep Medicine
DOI 10.1016/j.sleep.2012.10.015PMC PMC3745815
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Abstract

Objective To determine the pathologic substrates in patients with rapid eye movement (REM) sleep behavior disorder (RBD) with or without a coexisting neurologic disorder.Methods The clinical and neuropathologic findings were analyzed on all autopsied cases from one of the collaborating sites in North America and Europe, were evaluated from January 1990 to March 2012, and were diagnosed with polysomnogram (PSG)-proven or probable RBD with or without a coexisting neurologic disorder. The clinical and neuropathologic diagnoses were based on published criteria.Results 172 cases were identified, of whom 143 (83%) were men. The mean±SD age of onset in years for the core features were as follows - RBD, 62±14 (range, 20-93), cognitive impairment (n=147); 69±10 (range, 22-90), parkinsonism (n=151); 68±9 (range, 20-92), and autonomic dysfunction (n=42); 62±12 (range, 23-81). Death age was 75±9 years (range, 24-96). Eighty-two (48%) had RBD confirmed by PSG, 64 (37%) had a classic history of recurrent dream enactment behavior, and 26 (15%) screened positive for RBD by questionnaire. RBD preceded the onset of cognitive impairment, parkinsonism, or autonomic dysfunction in 87 (51%) patients by 10±12 (range, 1-61) years. The primary clinical diagnoses among those with a coexisting neurologic disorder were dementia with Lewy bodies (n=97), Parkinson's disease with or without mild cognitive impairment or dementia (n=32), multiple system atrophy (MSA) (n=19), Alzheimer's disease (AD)(n=9) and other various disorders including secondary narcolepsy (n=2) and neurodegeneration with brain iron accumulation-type 1 (NBAI-1) (n=1). The neuropathologic diagnoses were Lewy body disease (LBD)(n=77, including 1 case with a duplication in the gene encoding α-synuclein), combined LBD and AD (n=59), MSA (n=19), AD (n=6), progressive supranulear palsy (PSP) (n=2), other mixed neurodegenerative pathologies (n=6), NBIA-1/LBD/tauopathy (n=1), and hypothalamic structural lesions (n=2). Among the neurodegenerative disorders associated with RBD (n=170), 160 (94%) were synucleinopathies. The RBD-synucleinopathy association was particularly high when RBD preceded the onset of other neurodegenerative syndrome features.Conclusions In this large series of PSG-confirmed and probable RBD cases that underwent autopsy, the strong association of RBD with the synucleinopathies was further substantiated and a wider spectrum of disorders which can underlie RBD now are more apparent.

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  1. Schenck, 2005, Paradox lost – midnight in the battleground of sleep and dreams – violent moving nightmares, REM sleep behavior disorder extreme-nights, LLC
  2. Silber, 1992, REM sleep behavior disorder in parkinsonian syndromes, Sleep Res, 21, 313
  3. Silber, 1993, Abnormal REM sleep motor activity in untreated Parkinson’s disease, Sleep Res, 22, 274
  4. Tang, 2009, Gender effect in patients with REM sleep behavior disorder associated with multiple system atrophy compared with Parkinson’s disease and dementia with Lewy bodies, Neurology, 72, A325

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Metadata

Authors
Boeve, B. F., Silber, M. H., Ferman, T. J., Lin, S. C., Benarroch, E. E., Schmeichel, A. M., Ahlskog, J. E., Caselli, R. J., Jacobson, S., Sabbagh, M., Adler, C., Woodruff, B., Beach, T. G., Iranzo, A., Gelpi, E., Santamaria, J., Tolosa, E., Singer, C., Mash, D. C., Luca, C., Arnulf, I., Duyckaerts, C., Schenck, C. H., Mahowald, M. W., Dauvilliers, Y., Graff-Radford, N. R., Wszolek, Z. K., Parisi, J. E., Dugger, B., Murray, M. E., & Dickson, D. W.
Affiliations
  • Mayo Clinic (US)
  • Banner Sun Health Research Institute (US)
  • Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
  • University of Miami (US)
  • Inserm (FR)
  • University of Minnesota (US)
  • Centre Hospitalier Universitaire de Montpellier (FR)
Corresponding author
Boeve, B.F.
ORCID
Venue
Sleep Medicine
Publisher
Elsevier BV
Published
2013-08
Volume
14
Issue
8
Pages
754-762
ISSN
1389-9457 (ISSN-L)
DOI
10.1016/j.sleep.2012.10.015
PMC
PMC3745815
OpenAlex
W2097714090
Cited by
393
References
119
Citations by year
2026: 12 · 2025: 22 · 2024: 25 · 2023: 27 · 2022: 37 · 2021: 30 · 2020: 31 · 2019: 37 · 2018: 38 · 2017: 36 · 2016: 39 · 2015: 26 · 2014: 21 · 2013: 10
FWCI
20.30
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Sleep Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • American Academy of Neurology
  • National Institute on Aging (R01AG015866, AG016574, AG-19610, U01AG006786, AG015866, AG-006786, P30AG019610, P50AG016574)
  • National Institute of Neurological Disorders and Stroke (U24NS072026, P50NS072187)
Topics
  • Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
Keywords
rapid eye movement sleep behavior disorder, clinicopathological correlation, neuropathology, Lewy body disease, dementia with Lewy bodies, Parkinson's disease, multiple system atrophy, Alzheimer's disease, autonomic dysfunction, parkinsonism, cognitive impairment, alpha-synuclein, brain iron accumulation, neurodegeneration, dream enactment behavior, age of onset, disease progression
MeSH terms
Adult, Aged, Aged, 80 and over, Alzheimer Disease, Brain, Female, Humans, Male, Middle Aged, Narcolepsy, Parkinson Disease, Supranuclear Palsy, Progressive, Age of Onset, Multiple System Atrophy, REM Sleep Behavior Disorder, Lewy Body Disease, Young Adult, Cognitive Dysfunction

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