Clinicopathologic correlations in 172 cases of rapid eye movement sleep behavior disorder with or without a coexisting neurologic disorder

Abstract

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.

The Prevalence and Characteristics of REM Sleep without Atonia (RSWA) in Patients Taking Antidepressants

“…Our results are consistent with previous studies that demonstrate increased prevalence of RSWA in patients taking antidepressants. 15,20,21 We also found that this increased risk is not due to age, gender, and type of SSRI/SNRI or presence of OSA. The most recent theories about REM sleep initiation advocate for a double switch model that may be triggered by neurons that are located in the brainstem.…”

Parkinson risk in idiopathic REM sleep behavior disorder

“…Of the 21 with dementia, 18 had $1 cardinal parkinsonism manifestation (11 met full UK Brain Bank criteria for parkinsonism 23 ), and the remaining 3 had abnormal quantitative motor testing; therefore, most, if not all, had DLB. 11,16,24 Of 17 patients with PD, 8 had MCI at diagnosis. Therefore, we observed considerable overlap between parkinsonian and cognitive signs.…”

Nonamnestic mild cognitive impairment progresses to dementia with Lewy bodies

“…Two of these patients had postmortem studies and both had DLBD. Because idiopathic RBD can precede the onset of DLB by many years, 39 this raises the question of whether a history of probable RBD in the context of dementia should be diagnosed as DLB in the absence of other core features, even in the presence of memory impairment. With the current DLB criteria, patients with RBD and dementia may incorrectly be designated as clinically probable AD.…”