Clinicopathologic correlations in 172 cases of rapid eye movement sleep behavior disorder with or without a coexisting neurologic disorder
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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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There are still no direct biomarkers to establish dementia with Lewy bodies, but indicative biomarkers include reduced dopamine transporter uptake on SPECT or PET, reduced MIBG myocardial scintigraphy uptake, and polysomnographic confirmation of REM sleep without atonia.
“While there are still no direct biomarkers to establish dementia with Lewy bodies, indicative biomarkers include reduced dopamine transporter (DAT) uptake in the basal ganglia on single photon emission computerized tomography (SPECT) or PET imaging165, 166, reduced iodine‐metaiodobenzylguanidine (MIBG) myocardial scintigraphy uptake 165 , and polysomnographic confirmation of REM sleep without at”
From Mental health care for older adults: recent advances and new directions in clinical practice and research (2022) · cites this paper as [167]
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Self-citation
- 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)
- 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 · 2012: 1
- FWCI
- 20.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- 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 › 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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