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. 2017 Aug 1;40(8):zsx071.
doi: 10.1093/sleep/zsx071.

Prodromal Parkinsonism and Neurodegenerative Risk Stratification in REM Sleep Behavior Disorder

Thomas R Barber  1   2 , Michael Lawton  3 , Michal Rolinski  1   2   4 , Samuel Evetts  1   2 , Fahd Baig  1   2 , Claudio Ruffmann  1   2 , Aimie Gornall  1   5 , Johannes C Klein  1   2 , Christine Lo  6   7 , Gary Dennis  7 , Oliver Bandmann  6   7 , Timothy Quinnell  8 , Zenobia Zaiwalla  9 , Yoav Ben-Shlomo  3 , Michele T M Hu  1   2
Affiliations

Prodromal Parkinsonism and Neurodegenerative Risk Stratification in REM Sleep Behavior Disorder

Thomas R Barber et al. Sleep. .

Abstract

Objectives: Rapid eye movement (REM) sleep behavior disorder (RBD) is the most specific marker of prodromal alpha-synucleinopathies. We sought to delineate the baseline clinical characteristics of RBD and evaluate risk stratification models.

Methods: Clinical assessments were performed in 171 RBD, 296 control, and 119 untreated Parkinson's (PD) participants. Putative risk measures were assessed as predictors of prodromal neurodegeneration, and Movement Disorders Society (MDS) criteria for prodromal PD were applied. Participants were screened for common leucine-rich repeat kinase 2 (LRRK2)/glucocerebrosidase gene (GBA) gene mutations.

Results: Compared to controls, participants with RBD had higher rates of solvent exposure, head injury, smoking, obesity, and antidepressant use. GBA mutations were more common in RBD, but no LRRK2 mutations were found. RBD participants performed significantly worse than controls on Unified Parkinson's Disease Rating Scale (UPDRS)-III, timed "get-up-and-go", Flamingo test, Sniffin Sticks, and cognitive tests and had worse measures of constipation, quality of life (QOL), and orthostatic hypotension. For all these measures except UPDRS-III, RBD and PD participants were equally impaired. Depression, anxiety, and apathy were worse in RBD compared to PD participants. Stratification of people with RBD according to antidepressant use, obesity, and age altered the odds ratio (OR) of hyposmia compared to controls from 3.4 to 45.5. 74% (95% confidence interval [CI] 66%, 80%) of RBD participants met the MDS criteria for probable prodromal Parkinson's compared to 0.3% (95% CI 0.009%, 2%) of controls.

Conclusions: RBD are impaired across a range of clinical measures consistent with prodromal PD and suggestive of a more severe nonmotor subtype. Clinical risk stratification has the potential to select higher risk patients for neuroprotective interventions.

Keywords: Neurodegeneration; Parkinson’s Disease; Prodromal; RBD.

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References

    1. Iranzo A, Santamaria J, Tolosa E. Idiopathic rapid eye movement sleep behaviour disorder: diagnosis, management, and the need for neuroprotective interventions. Lancet Neurol. 2016; 15(4): 405–419. - 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. - 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. - PubMed
    1. Wing YK, Li SX, Mok V, et al. Prospective outcome of rapid eye movement sleep behaviour disorder: psychiatric disorders as a potential early marker of Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2012; 83(4): 470–472. - PubMed
    1. Postuma RB, Iranzo A, Hogl B, et al. Risk factors for neurodegeneration in idiopathic rapid eye movement sleep behavior disorder: a multicenter study. Ann Neurol. 2015; 77(5): 830–839. - PMC - PubMed

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