REM sleep behavior disorder (RBD) is a strong predictor of neurodegenerative disease, according to research published in the January 7 online Neurology. Just how strong? More than half of patients with idiopathic RBD will develop either Parkinson’s disease or Lewy body dementia within 12 years of their first RBD symptoms, reported Ronald B. Postuma, MD, and colleagues.
The connection between early RBD and later disease has been recognized previously, but the study by the Sacré-Coeur Sleep Disorders Center in Montreal is the largest to date and provides risk assessment for much longer periods after RBD symptom development than do earlier studies. Although there is not yet any way to alter the risk, “we have to know what to tell our patients,” said Dr. Postuma, Assistant Professor in the Department of Neurology at McGill University in Montreal, who led the research along with Jacques Montplaisir, MD, Professor of Psychiatry and Neuroscience at the University of Montreal and the Director of the Sleep Disorders Center at Hôpital du Sacré-Coeur.
A Neurodegenerative Link?
RBD and Parkinson’s disease are believed to be linked through the same neurodegenerative process. Within the past decade, it has become clear that in most cases, the Parkinson’s disease process starts not in the substantia nigra but in olfactory and autonomic areas and then spreads to other brain regions, including those that regulate sleep. “What we think is going on is that the pathologic process of Parkinson’s disease is present in many people with REM sleep behavior disorder,” said Dr. Postuma, who is also a researcher at Hôpital du Sacré-Coeur.
To study that connection further, the investigators performed follow-up on 93 patients who were diagnosed with idiopathic RBD. The mean delay between onset of RBD symptoms and diagnosis was 7.2 years. None of the patients had signs of any neurodegenerative disorder at diagnosis. The mean age at diagnosis was 65, and 80% were male.
After a mean follow-up of 5.2 years, 26 patients had some form of neurodegenerative disease. Fourteen had a diagnosis of Parkinson’s disease, one had multiple system atrophy, and 11 had dementia. Of the patients with dementia, seven met criteria for Lewy body dementia; the remaining four did not show the necessary clinical signs for a Lewy body dementia diagnosis (parkinsonism, visual hallucinations, or fluctuations) and had received a diagnosis of Alzheimer’s disease.
Dr. Postuma noted that despite the diagnosis of Alzheimer’s disease, these four patients likely also had Lewy body dementia. Parkinsonism and other clinical signs may not appear early in the disease, he said, making misdiagnosis as Alzheimer’s disease more likely. After the study, his group has continued to follow these patients, and early indications are that Lewy body dementia is the correct diagnosis in these patients as well.
Quantifying the Risk
Dr. Postuma and colleagues calculated the risk for Parkinson’s disease or dementia from time of RBD symptom onset. The risk after five, 10, and 12 years increased linearly over time at 18%, 41%, and 52%, respectively. They pointed out that these risk estimates are slightly lower than those from earlier reports; however, those studies included smaller numbers of patients and used broader criteria for diagnosis of neurodegenerative disease. “It is also possible that disease risk can be changing with time, perhaps related to earlier diagnosis and recognition of milder cases,” the researchers said. In support of this, Dr. Postuma noted that within his own patient cohort, the delay between RBD symptom onset and diagnosis has decreased significantly during the past 20 years.
The fact that such a large proportion of patients with RBD will later manifest a neurodegenerative disease “suggests that an opportunity exists for neuroprotective measures in the preclinical stage of the disease,” Dr. Postuma said. The growing body of data on the natural history of RBD would make patients with this disorder not only important targets of early neuroprotective treatment, once it exists, but also ideal clinical research subjects for neuroprotective trials as well. He noted that about half of patients with RBD also display other signs associated with preclinical Parkinson’s disease, such as loss of sense of smell or autonomic dysfunction.
Dr. Postuma recommends closely following patients with RBD once they are diagnosed. As for what to tell them about their future risk, “it’s a difficult issue,” he said. “I often tell patients, ‘You have a sleep disorder, and it carries a risk for other neurologic disorders, and therefore I think I should follow you every year.’ After that, it depends on what the patient wants to know.”
He added that he would not start patients on any medication that is being investigated for neuroprotection in Parkinson’s disease. Despite some intriguing clinical results, “we don’t have an agent yet,” he said.