Conference Coverage

REM sleep problems predict Parkinson's, Lewy body dementia



SAN DIEGO – REM sleep behavior disorder is the earliest indication that patients are destined to develop Parkinson’s disease, Lewy body dementia, or another synucleinopathy; it precedes the onset of motor and cognitive problems by years, according to a growing body of research.

Its presence also distinguishes synucleinopathies from Alzheimer’s disease and other problems that can have similar early presentations.

Dr. Ronald B. Postuma

REM sleep behavior disorder (RBD) "diagnoses disease" and "identifies prodromal disease. The rule is very simple: RBD equals synucleinopathy, and it works almost every time," said Dr. Ronald Postuma of the department of neurology at McGill University in Montreal, and a leading researcher in the field.

"The way I explain RBD to patients is that ‘normally, when most people dream, they are paralyzed, but you are not. Therefore, you are capable of acting out the content of your dreams.’ Injury is relatively common," he said, but RBD can be subtle, too, with no more than gestures during sleep.

Dr. Postuma made his comments at the annual meeting of the American Academy of Neurology, following the presentation there of a new addition to the evidence base, an autopsy study led by the Mayo Clinic in Rochester, Minn., and recently published online (Sleep Med. 2013 [doi:10.1016/j.sleep.2012.10.015]).

The Mayo team analyzed neuropathologic findings from 172 patients diagnosed with RBD before death. They found that "among [the 170] neurodegenerative disorders associated with RBD, 160 (94%) were synucleinopathies." Among them were 136 patients with Lewy bodies and 19 with multiple-system atrophy. The remaining few had findings consistent with Alzheimer’s disease or other nonsynucleinopathies.

In life, RBD was diagnosed at a mean age of 62 years of age. It preceded the eventual diagnosis of Parkinsonism in 151 patients by a mean of 6 years. The diagnosis of RBD preceded death by a mean of 13 years.

"Lewy body disease was by far the most common underlying neurologic disorder. The chunk of the rest was multiple-system atrophy. We’ve been looking for [cases of] Alzheimer’s associated with RBD for well over 10 years, and they are just hard to find." The findings "again underscore the selectivity of RBD for synucleinopathy. [They] argue that the selective vulnerability involves ... REM sleep circuitry," said lead investigator Dr. Bradley Boeve, chair of the division of behavioral neurology at Mayo.

Most of the subjects (83%) were men. Eighty-two were diagnosed with RBD by polysomnography, the gold-standard; 98% of the PSG-confirmed cases had a synucleinopathy at autopsy, Dr. Boeve noted.

The remainder had been diagnosed by history, which "can really be quite good" so long as sleep apnea and other confounders are kept in mind, said Dr. Postuma, who was not involved in the project.

The take-home message is that "if you have a patient with a neurodegenerative disorder in front of you, if the patient doesn’t have RBD and that patient is demented, the chances are [that they don’t] have [Lewy body dementia]. In contrast, if you have a pretty good history of RBD but don’t have a PSG [polysomnography] to confirm it, there’s a 94% chance that you have a synucleinopathy. If you do have PSG, there’s a 98% chance of having a synucleinopathy," Dr. Postuma said.

"I don’t think there is any marker in clinical medicine that has anything close to this amount of relative risk for developing a neurodegenerative disease. This is completely unique. Asking about REM sleep behavior disorder in your clinics tomorrow will help you diagnose disease," he said.

Investigators from Barcelona, Spain, came to similar conclusions in a paper published online April 2 in Lancet Neurology (doi:10.1016/S1474-4422[13]70056-5).

For most, RBD "represents the prodromal phase of a Lewy body disorder ... such as Parkinson’s disease (PD) or dementia with Lewy bodies. ... [RBD] is a candidate for the study of early events and progression of this prodromal phase, and to test disease-modifying strategies to slow or stop the neurodegenerative process," they concluded.

The Spanish team followed 44 RBD cases diagnosed between 1991 and 2003. By 2012, 36 (82%) had developed a synucleinopathy, among them 16 patients with Parkinson’s disease, 14 with Lewy body dementia, and 1 with multiple system atrophy. "The rates of neurological-disease-free survival from time of [RBD] diagnosis were 65.2% at 5 years, 26.6% at 10 years, and 7.5% at 14 years," they reported.

Most RBD patients "developed a Lewy body disorder with time. Patients who remained disease-free at follow-up showed markers of increased short-term risk for developing PD," including lesions "in the brainstem nuclei that regulate REM sleep atonia," the Spanish researchers found.

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