Association of REM sleep behavior disorder and neurodegenerative disease may reflect an underlying synucleinopathy

Our objective was to examine whether rapid eye movement (REM) sleep behavio r disorder occurs in disproportionally greater frequency in multiple system atrophy (MSA), Parkinson's disease (PD), and dementia with Lewy bodies (DL B), collectively known as the synucleinopathies, compared to other nonsynuc leinopathy neurodegenerative disorders. In study 1, we reviewed the clinical records of 398 consecutive patients ev aluated at Mayo Clinic Rochester for parkinsonism and/or cognitive impairme nt. The frequency of suspected and polysomnogram (PSG)-confirmed REM sleep behavior disorder (RBD) among subjects with the synucleinopathies MSA, PD, or DLB was compared to the frequency among subjects with the nonsynucleinop athies Alzheimer's disease (AD), frontotemporal dementia (FTD), corticobasa l degeneration (CBD), progressive supranuclear palsy (PSP), mild cognitive impairment (MCI), primary progressive aphasia (PPA), and posterior cortical atrophy (PCA). In study 2, we reviewed the clinical records of 360 consecu tive patients evaluated at Mayo Clinic Jacksonville for parkinsonism and/or cognitive impairment. The frequency of probable RBD among patients with PD and DLB was compared to the frequency among patients with AD and MCI. In s tudy 3, we reviewed the brain biopsy or postmortem autopsy diagnoses of 23 Mayo Clinic Rochester patients who had been clinically examined for possibl e RBD and a neurodegenerative disorder. In study 1, patients with MSA, PD, or DLB were more likely to have probable and PSG-confirmed RBD compared to subjects with the nonsynucleinopathies ( probable RBD 77/120=64% vs. 7/278=3%, p < 0.01; PSG-confirmed RBD 47/120=39 % vs. 1/278=0%, p < 0.01). In study 2, patients with PD and DLB were more l ikely to have probable RBD compared to those with AD and MCI (56% vs. 2%, p < 0.01). In study 3, of the 23 autopsied patients who had been questioned about possible RBD, 10 were clinically diagnosed with RBD. The neuropatholo gic diagnoses in these 10 included Lewy body disease in nine, and MSA in on e. Of the other 13 cases, 12 did not have a history suggesting RBD, and the one case who did had normal electromyographic atonia during REM sleep on P SG and autopsy findings of PSP. Only one of these 13 had a synucleinopathy. The positive predictive values for RBD indicating a synucleinopathy for st udies 1-3 were 91.7%, 94.3%, and 100.0%, respectively. Clinically suspected and PSG-proven RBD occurs with disproportionally great er frequency in VISA, PD, and DLB compared to other neurodegenerative disor ders. In the setting of degenerative dementia and/or parkinsonism, we hypot hesize that RBD is a manifestation of an evolving synucleinopathy. (C) 2001 Movement Disorder Society.