REM sleep behavior disorder predicts impending synucleinopathy

 

LOS ANGELES – At least 70% of patients with idiopathic REM sleep behavior disorder will develop a neurodegenerative disease within about a decade, according to a years-long, multicenter investigation of 1,280 patients – the largest study of the issue to date.

REM sleep behavior disorder (RBD) has been known for years to increase the risk for synucleinopathies, namely Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. However, previous studies have mostly been conducted at single institutions, so the exact extent to which RBD increases the risk wasn’t clear.

M. Alexander Otto/MDEdge News

The new investigation lays the issue to rest. It nailed “down a precise and generalizable” estimate, according to lead investigator Ronald Postuma, MD, a movement disorder specialist at McGill University, Montreal. “What we found overall is that the risk is 6.3% per year; 50% of patients phenoconvert at 7.5 years, and at 12 years, we are up to 73%. This is quite striking. The bottom line is if you have a patient with polysomnographic-proven RBD in front of you, you are talking to [someone] destined to develop a neurodegenerative disease in the next 10 to 12 years,” he said.

These findings have important implications for the field. Now that it’s known who’s at risk, “we have a chance to do neuroprotective therapy. It’s time to move forward and start preventing disease,” Dr. Postuma said at the American Academy of Neurology annual meeting. He estimated that it would take only a few hundred patients to do a 2-year trial of neuroprotective therapy.

The 1,280 study subjects were culled from 24 sleep centers on four continents, all participants in the international RBD study group. The patients needed for a trial “are sitting right now” in the study group, “so maybe we can get on with this,” he said.

REM sleep – the dream state – normally paralyzes people, but something breaks down in RBD, and people act out their dreams, sometimes to disturbing effects. It occurs in about 1% of the population, usually in older people and in slightly more men than women.

The risk of neurodegenerative disease in RBD increases even more if patients test positive at baseline for movement declines, cognitive issues, olfactory problems, constipation, color vision loss, erectile dysfunction, or abnormal dopamine transporter scans. Dr. Postuma and his team found no predictive value for somnolence, insomnia, urinary problems, depression, or anxiety. These negative findings were surprising, he said, because mood disorders and sleep troubles are known to increase the risk in the general population.

 

The subjects all had polysomnographic-proven RBD at baseline, without neurodegenerative disease. Most of them were men and were about 70 years old, on average. Subjects were tested for synucleinopathies and risk variables annually. The mean disease-free follow-up was about 4 years, but ranged out to 19 years. Risks were adjusted for age, sex, and study center.

Cognition deficits were the only thing that distinguished future dementia patients from those destined for movement disorders. “Everything [else] is really the same between who gets dementia and who gets Parkinsonism,” Dr. Postuma said.

The study was funded by the Canadian Institute of Health Research and the Fonds de la Recherche Sante Quebec. Dr. Postuma disclosed consulting, speaking, and other fees from Biotie, Roche/Prothena, Teva Neurosciences, Novartis Canada, Theranexus, Jazz Pharmaceuticals, and GE HealthCare.

[email protected]

SOURCE: Postuma R et al. AAN 2018, plenary session.

 

LOS ANGELES – At least 70% of patients with idiopathic REM sleep behavior disorder will develop a neurodegenerative disease within about a decade, according to a years-long, multicenter investigation of 1,280 patients – the largest study of the issue to date.

REM sleep behavior disorder (RBD) has been known for years to increase the risk for synucleinopathies, namely Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. However, previous studies have mostly been conducted at single institutions, so the exact extent to which RBD increases the risk wasn’t clear.

M. Alexander Otto/MDEdge News

The new investigation lays the issue to rest. It nailed “down a precise and generalizable” estimate, according to lead investigator Ronald Postuma, MD, a movement disorder specialist at McGill University, Montreal. “What we found overall is that the risk is 6.3% per year; 50% of patients phenoconvert at 7.5 years, and at 12 years, we are up to 73%. This is quite striking. The bottom line is if you have a patient with polysomnographic-proven RBD in front of you, you are talking to [someone] destined to develop a neurodegenerative disease in the next 10 to 12 years,” he said.

These findings have important implications for the field. Now that it’s known who’s at risk, “we have a chance to do neuroprotective therapy. It’s time to move forward and start preventing disease,” Dr. Postuma said at the American Academy of Neurology annual meeting. He estimated that it would take only a few hundred patients to do a 2-year trial of neuroprotective therapy.

The 1,280 study subjects were culled from 24 sleep centers on four continents, all participants in the international RBD study group. The patients needed for a trial “are sitting right now” in the study group, “so maybe we can get on with this,” he said.

REM sleep – the dream state – normally paralyzes people, but something breaks down in RBD, and people act out their dreams, sometimes to disturbing effects. It occurs in about 1% of the population, usually in older people and in slightly more men than women.

The risk of neurodegenerative disease in RBD increases even more if patients test positive at baseline for movement declines, cognitive issues, olfactory problems, constipation, color vision loss, erectile dysfunction, or abnormal dopamine transporter scans. Dr. Postuma and his team found no predictive value for somnolence, insomnia, urinary problems, depression, or anxiety. These negative findings were surprising, he said, because mood disorders and sleep troubles are known to increase the risk in the general population.

 

The subjects all had polysomnographic-proven RBD at baseline, without neurodegenerative disease. Most of them were men and were about 70 years old, on average. Subjects were tested for synucleinopathies and risk variables annually. The mean disease-free follow-up was about 4 years, but ranged out to 19 years. Risks were adjusted for age, sex, and study center.

Cognition deficits were the only thing that distinguished future dementia patients from those destined for movement disorders. “Everything [else] is really the same between who gets dementia and who gets Parkinsonism,” Dr. Postuma said.

The study was funded by the Canadian Institute of Health Research and the Fonds de la Recherche Sante Quebec. Dr. Postuma disclosed consulting, speaking, and other fees from Biotie, Roche/Prothena, Teva Neurosciences, Novartis Canada, Theranexus, Jazz Pharmaceuticals, and GE HealthCare.

[email protected]

SOURCE: Postuma R et al. AAN 2018, plenary session.

 

LOS ANGELES – At least 70% of patients with idiopathic REM sleep behavior disorder will develop a neurodegenerative disease within about a decade, according to a years-long, multicenter investigation of 1,280 patients – the largest study of the issue to date.

REM sleep behavior disorder (RBD) has been known for years to increase the risk for synucleinopathies, namely Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. However, previous studies have mostly been conducted at single institutions, so the exact extent to which RBD increases the risk wasn’t clear.

M. Alexander Otto/MDEdge News

The new investigation lays the issue to rest. It nailed “down a precise and generalizable” estimate, according to lead investigator Ronald Postuma, MD, a movement disorder specialist at McGill University, Montreal. “What we found overall is that the risk is 6.3% per year; 50% of patients phenoconvert at 7.5 years, and at 12 years, we are up to 73%. This is quite striking. The bottom line is if you have a patient with polysomnographic-proven RBD in front of you, you are talking to [someone] destined to develop a neurodegenerative disease in the next 10 to 12 years,” he said.

These findings have important implications for the field. Now that it’s known who’s at risk, “we have a chance to do neuroprotective therapy. It’s time to move forward and start preventing disease,” Dr. Postuma said at the American Academy of Neurology annual meeting. He estimated that it would take only a few hundred patients to do a 2-year trial of neuroprotective therapy.

The 1,280 study subjects were culled from 24 sleep centers on four continents, all participants in the international RBD study group. The patients needed for a trial “are sitting right now” in the study group, “so maybe we can get on with this,” he said.

REM sleep – the dream state – normally paralyzes people, but something breaks down in RBD, and people act out their dreams, sometimes to disturbing effects. It occurs in about 1% of the population, usually in older people and in slightly more men than women.

The risk of neurodegenerative disease in RBD increases even more if patients test positive at baseline for movement declines, cognitive issues, olfactory problems, constipation, color vision loss, erectile dysfunction, or abnormal dopamine transporter scans. Dr. Postuma and his team found no predictive value for somnolence, insomnia, urinary problems, depression, or anxiety. These negative findings were surprising, he said, because mood disorders and sleep troubles are known to increase the risk in the general population.

 

The subjects all had polysomnographic-proven RBD at baseline, without neurodegenerative disease. Most of them were men and were about 70 years old, on average. Subjects were tested for synucleinopathies and risk variables annually. The mean disease-free follow-up was about 4 years, but ranged out to 19 years. Risks were adjusted for age, sex, and study center.

Cognition deficits were the only thing that distinguished future dementia patients from those destined for movement disorders. “Everything [else] is really the same between who gets dementia and who gets Parkinsonism,” Dr. Postuma said.

The study was funded by the Canadian Institute of Health Research and the Fonds de la Recherche Sante Quebec. Dr. Postuma disclosed consulting, speaking, and other fees from Biotie, Roche/Prothena, Teva Neurosciences, Novartis Canada, Theranexus, Jazz Pharmaceuticals, and GE HealthCare.

[email protected]

SOURCE: Postuma R et al. AAN 2018, plenary session.