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REM sleep behavior disorder preceding other aspects of synucleinopathies by up to half a century
Claassen DO, Josephs KA, Ahlskog JE, Silber MH, Tippmann-Peikert M, Boeve BF.. Neurology, 2010-07-28
Topic: Brain proteins, microglia and lab models
Background Idiopathic REM sleep behavior disorder (RBD) may be the initial manifestation of synucleinopathies (Parkinson disease [PD], multiple system atrophy [MSA], or dementia with Lewy bodies [DLB]). Methods We used the Mayo medical records linkage system to identify cases presenting from 2002 to 2006 meeting the criteria of idiopathic RBD at onset, plus at least 15 years between RBD and development of other neurodegenerative symptoms. All patients underwent evaluations by specialists in sleep medicine to confirm RBD, and behavioral neurology or movement disorders to confirm the subsequent neurodegenerative syndrome. Results Clinical criteria were met by 27 patients who experienced isolated RBD for at least 15 years before evolving into PD, PD dementia (PDD), DLB, or MSA. The interval between RBD and subsequent neurologic syndrome ranged up to 50 years, with the median interval 25 years. At initial presentation, primary motor symptoms occurred in 13 patients: 9 with PD, 3 with PD and mild cognitive impairment (MCI), and 1 with PDD. Primary cognitive symptoms occurred in 13 patients: 10 with probable DLB and 3 with MCI. One patient presented with primary autonomic symptoms, diagnosed as MSA. At most recent follow-up, 63% of patients progressed to develop dementia (PDD or DLB). Concomitant autonomic dysfunction was confirmed in 74% of all patients. Conclusions These cases illustrate that the alpha-synuclein pathogenic process may start decades before the first symptoms of PD, DLB, or MSA. A long-duration preclinical phase has important implications for epidemiologic studies and future interventions designed to slow or halt the neurodegenerative process.
Key findings
- Results Clinical criteria were met by 27 patients who experienced isolated RBD for at least 15 years before evolving into PD, PD dementia (PDD), DLB, or MSA.
Why it matters
Acting out dreams during sleep (REM sleep behavior disorder) appeared up to 50 years (median 25) before Parkinson's disease, dementia with Lewy bodies or multiple system atrophy in 27 Mayo Clinic patients, and 63% of them eventually developed dementia. The authors say this suggests the alpha-synuclein disease process "may start decades before the first symptoms." Every patient was chosen because they had already developed one of these conditions, so the study cannot say how likely someone with this sleep disorder is to develop one.
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Study details
- Participants27
- Evidence strengthLow
How this study scored 57/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2010 — within 20 year(s) of the newest study here |
| Sample size | 1 / 4 | 27 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 392 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 21.8 citations a year over 18 year(s) since 2010 |
| Impact for its field and year | 5 / 6 | Cited 24.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 10 other studies in this library |
| Still being cited | 2 / 4 | Cited 34 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Bradley F. Boeve: h-index 173 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Mayo Clinic: institution h-index 1,606 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 20668263) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 57 / 100 | — |
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Claassen, D. O., Josephs, K. A., Ahlskog, J. E., Silber, M. H., Tippmann-Peikert, M., & Boeve, B. F. (2010). REM sleep behavior disorder preceding other aspects of synucleinopathies by up to half a century. Neurology. https://doi.org/10.1212/wnl.0b013e3181ec7fac
Vancouver
Claassen DO, Josephs KA, Ahlskog JE, Silber MH, Tippmann-Peikert M, Boeve BF. REM sleep behavior disorder preceding other aspects of synucleinopathies by up to half a century. Neurology. 2010. doi:10.1212/wnl.0b013e3181ec7fac. PMID: 20668263.
BibTeX
@article{claassen2010-20668263,
author = {Claassen, D. O. and Josephs, K. A. and Ahlskog, J. E. and Silber, M. H. and Tippmann-Peikert, M. and Boeve, B. F.},
title = {{REM sleep behavior disorder preceding other aspects of synucleinopathies by up to half a century}},
journal = {Neurology},
year = {2010},
doi = {10.1212/wnl.0b013e3181ec7fac},
pmid = {20668263},
url = {https://doi.org/10.1212/wnl.0b013e3181ec7fac}
}
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