REM Sleep Problems Predict Parkinson's, Lewy Body Dementia

Abstract

SAN DIEGO – Rapid eye movement (REM) sleep behavior disorder (RBD) is the earliest indication that elderly patients are destined to develop Parkinson's disease, Lewy body dementia, or another synucleinopathy, and 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. RBD “equals synucleinopathy,” said Dr. Ronald Postuma of the department of neurology at McGill University in Montreal. “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.” Dr. Postuma made his comments at the annual meeting of the American Academy of Neurology. Also there, researchers from the Mayo Clinic in Rochester, Minn., presented an autopsy study, now published in Sleep Medicine. The Mayo team analyzed neuropathologic findings from 172 patients diagnosed with RBD before death. They found that 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. RBD was diagnosed at a mean age of 62 years. It preceded the 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. … We've been looking for [cases of] Alzheimer's associated with RBD for well over 10 years, and they are just hard to find,” said lead investigator Dr. Bradley Boeve, chair of the division of behavioral neurology at Mayo. The findings “argue that the selective vulnerability involves … REM sleep circuitry.” At autopsy, 98% of polysomnography (PSG)-confirmed cases had a synucleinopathy, Dr. Boeve noted. The take-home message is that “if you have a pretty good history of RBD but don't have a PSG 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. “Asking about REM sleep behavior disorder in your clinics tomorrow will help you diagnose disease.” Investigators from Barcelona, Spain, came to similar conclusions in a paper published recently in Lancet Neurology (Lancet Neurol. 2013;12[5]:443-53). 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, 82% had developed a synucleinopathy: 16 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. Asked to comment on the Spanish study, Dr. Postuma said that the findings “emphatically confirm the incredible risk that patients with RBD have for developing neurodegenerative disease.” The ability to identify a neurodegenerative disease 10 years before it can be diagnosed “provides profound opportunities to study early stages of disease.” Dr. Boeve's research has been supported by Cephalon, Allon Therapeutics, and GE Healthcare. Dr. Postuma disclosed personal support from Teva and Novartis.