Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Nov 26;103(10):e209993.
doi: 10.1212/WNL.0000000000209993. Epub 2024 Oct 25.

Phenoconversion in Women and Men With Isolated REM Sleep Behavior Disorder: A Retrospective Cohort Study

Christina A Alexandres  1 , Stuart J McCarter  1 , Grace M Tabatabai  1 , Laurene LeClair-Visonneau  1 , John C Feemster  1 , Thomas R Gossard  1 , Emma P Strainis  1 , Jack T Jagielski  1 , Makayla R Kelleher  1 , Thomas Finstuen  1 , Farwa Ali  1 , Hugo Botha  1 , Jonathan Graff-Radford  1 , Eric J Olson  1 , David J Sandness  1 , Timothy J Morgenthaler  1 , Kejal Kantarci  1 , Rodolfo Savica  1 , Wolfgang Singer  1 , Naima Covassin  1 , Virend K Somers  1 , James L Kirkland  1 , Mithri Junna  1 , Melissa Lipford  1 , Christine A Matarese  1 , James L Moore  1 , Maja Tippmann-Peikert  1 , Diego Z Carvalho  1 , Bradley F Boeve  1 , Michael H Silber  1 , Erik K St Louis  1
Affiliations

Phenoconversion in Women and Men With Isolated REM Sleep Behavior Disorder: A Retrospective Cohort Study

Christina A Alexandres et al. Neurology. .

Abstract

Background and objectives: Isolated REM sleep behavior disorder (iRBD) is strongly associated with synucleinopathies. Previous iRBD cohort studies have primarily focused on older (>50 years), male-predominant cohorts. Risk of phenoconversion in women and younger adults remains unclear. The study aimed to determine clinical features associated with conversion to a defined neurodegenerative disorder in women and men with iRBD.

Methods: One hundred eighty-six women and 186 men with iRBD were matched by polysomnography month. Baseline clinical variables and subsequent neurodegenerative outcomes were abstracted by chart review. Kaplan-Meier curves assessed conversion rates. Cox proportional hazards modeling evaluated factors associated with phenoconversion risk.

Results: Age at iRBD diagnosis was younger in women compared with men (54.9 vs 62.5 years, p < 0.01). Forty-eight patients (12.9%), including 18 women (9.7%) and 30 men (16.1%), phenoconverted during a median follow-up of 6.0 years. Conversion rates were lower in antidepressant users and patients with chronic pain or psychiatric comorbidity while rates were higher in those with vascular comorbidity. Only age at diagnosis (HR 1.09, 95% CI 1.06-1.13) was associated with phenoconversion after adjusting for RBD symptom duration; sex; antidepressant use; and psychiatric, chronic pain, and vascular comorbidities.

Discussion: Age at diagnosis was independently associated with phenoconversion risk in women and men with iRBD.

PubMed Disclaimer

Conflict of interest statement

C. Alexandres, S.J. McCarter, G. Tabatabai, L. LeClair-Visonneau, J. Feemster, T. Gossard, E. Strainis, J. Jagielski, M. Kelleher, T. Finstuen, F. Ali, H. Botha, J. Graff Radford, E.J. Olson, D. Sandness, T.I. Morgenthaler, K. Kantarci, R. Savica, and W. Singer report no relevant disclosures. N. Covassin reports grant support from Sleep Number Corp. V.K. Somers reports being a consultant for Zoll, Jazz, Lilly, Huxley, ApniMed and ResMed and serving on the Sleep Number Corporation Scientific Advisory Board. Funding received from NIH and grants from Sleep Number to Mayo Clinic. J.L. Kirkland reports grant support from the NIH (R33AG61456 and R37AG13925), the Alzheimer's Association (PTC REG-20-651687), the Connor Fund, Robert J. and Theresa W. Ryan, and the Noaber Foundation. J.L. Kirkland, M. Junna, M. Lipford, C. Matarese, J.L. Moore, and M. Tippmann-Peikert report no relevant disclosures. D.Z. Carvalho reports grant support from the National Institute of Aging. B.F. Boeve and M.H. Silber report no relevant disclosures. E.K. St. Louis reports grant support from the NIH (National Institutes of Aging, Neurologic Disorders, and Heart Lung and Blood), and from Sleep Number, Inc. and Spark, Inc. Go to Neurology.org/N for full disclosures.

Figures

Figure
Figure. Phenoconversion in Isolated REM Sleep Behavior Disorder in 372 Women and Men in the Mayo Clinic Cohort
The phenoconversion failure curves are shown. (A) The overall cohort: 48 patients (12.9%) phenoconverted to neurodegenerative disorders, with 5-year, 10-year, and 14-year conversion rates of 6%, 24%, and 32%, respectively. (B) Women and men, demonstrating similar rates. (C) Antidepressant users/nonusers, for whom conversion was less likely in users than in nonusers (p < 0.001). (D) Patients having or not having vascular comorbidities, for whom conversion was greater in those having than not having vascular comorbidities (p = 0.001). Only age at diagnosis was independently associated with phenoconversion risk (also in Table 2). (E) Phenoconversion stratified by age at RBD diagnosis. For RBD diagnosis before age 50 years, the annualized conversion risk was 0.11% per year (5-year, 10-year, and 14-year conversion rates of 0%, 1.6%, and 1.6%). For diagnosis age 50–60 years, the annualized risk was 0.64% per year (5-year, 10-year, and 14-year rates of 2.5%, 9%, and 9%). For diagnosis age 60–70 years, the annualized risk was 2.6% (5-year, 10-year, and 14-year rates of 6%, 22%, and 36%). After age 70, annualized conversion rate was 6% (5-year, 10-year, and 14-year rates of 15%, 67%, and 84%). RBD = REM sleep behavior disorder.
See this image and copyright information in PMC

References

    1. Iranzo A, Molinuevo JL, Santamaría J, et al. Rapid-eye-movement sleep behaviour disorder as an early marker for a neurodegenerative disorder: a descriptive study. Lancet Neurol. 2006;5(7):572-577. doi: 10.1016/S1474-4422(06)70476-8 - DOI - PubMed
    1. Postuma RB, Gagnon JF, Vendette M, Fantini ML, Massicotte-Marquez J, Montplaisir J. Quantifying the risk of neurodegenerative disease in idiopathic REM sleep behavior disorder. Neurology. 2009;72(15):1296-1300. doi: 10.1212/01.wnl.0000340980.19702.6e - DOI - PMC - PubMed
    1. Schenck CH, Boeve BF, Mahowald MW. Delayed emergence of a parkinsonian disorder or dementia in 81% of older men initially diagnosed with idiopathic rapid eye movement sleep behavior disorder: a 16-year update on a previously reported series. Sleep Med. 2013;14(8):744-748. doi: 10.1016/j.sleep.2012.10.009 - DOI - PubMed
    1. Iranzo A, Fernández-Arcos A, Tolosa E, et al. Neurodegenerative disorder risk in idiopathic REM sleep behavior disorder: study in 174 patients. PLoS One. 2014;9(2):e89741. doi: 10.1371/journal.pone.0089741 - DOI - PMC - PubMed
    1. Bodkin CL, Schenck CH. Rapid eye movement sleep behavior disorder in women: relevance to general and specialty medical practice. J Womens Health (Larchmt). 2009;18(12):1955-1963. doi: 10.1089/jwh.2008.1348 - DOI - PubMed

LinkOut - more resources