REM sleep behaviour disorder becomes Parkinson's

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Carlos Schenck, Scott Bundlie and Mark Mahowald (Minnesota Regional Sleep Disorders Center, Minneapolis) in 1996. Ronald Postuma (McGill University, Montreal), Alex Iranzo, Birgit Högl, Bradley Boeve and colleagues of the International RBD Study Group in 2019. Funders are not stated in the abstracts.

What happened

In REM sleep, muscles normally go limp. In RBD they do not, and people shout, punch or kick as they dream. When there is no other cause, it is called isolated (iRBD).

• 1996. Schenck followed 29 men aged 50 or older diagnosed with iRBD. 38% (11 of 29) were later diagnosed with a parkinsonian disorder, on average 3.7 years after the RBD diagnosis and 12.7 years after the RBD began. Only 2 of 29 developed another neurological disorder. (Neurology 46:388–393.)
• 2013 update by the same group. 21 of 26 men still followed (80.8%) had developed parkinsonism or dementia: 13 Parkinson's, 3 dementia with Lewy bodies, 2 multiple system atrophy, and others. The average gap from RBD onset was 14.2 years, with a range of 5 to 29 years.
• 2019. Postuma et al. combined prospective data from 24 centres on 1,280 people with sleep-lab-confirmed iRBD and no parkinsonism or dementia at the start. Average age 66.3; 82.5% male; average follow-up 4.6 years (range 1–19). Overall conversion to an overt neurodegenerative syndrome was 6.3% per year, and 73.5% had converted by 12 years. (Brain 142:744–759, DOI 10.1093/brain/awz030.)
• Who converts sooner. Hazard ratios for faster conversion included abnormal quantitative motor testing 3.16, abnormal motor examination 3.03, loss of smell 2.62, mild cognitive impairment 1.91–2.37, erectile dysfunction 2.13, abnormal dopamine-transporter scan 1.98, constipation 1.67.
• Trial size. The authors estimated that a definitive neuroprotection trial would need 142 to 366 people per arm.

Why it moved us toward a cure

Slowing drugs may work best before the motor symptoms start, when most dopamine neurons are still alive. iRBD gives a group that can be found years ahead and that converts at a known, high rate, so a trial can use time to conversion as its measure. It also supplies the entry group for the prodromal criteria (landmark 222) and the prevention trials (landmark 225). No earlier landmark is its parent; the finding came from sleep medicine.

Outcome

Advanced. iRBD cohorts are now the main recruitment pool for prevention trials. Limits: the groups come from sleep clinics and are mostly male, the end point is any synuclein disease (Parkinson's, dementia with Lewy bodies or multiple system atrophy), not Parkinson's alone, and no drug has yet been shown to delay conversion.

Sources

• Schenck, Bundlie, Mahowald, Neurology 1996;46:388–393, DOI 10.1212/wnl.46.2.388, PMID 8614500 (Europe PMC)
• Schenck, Boeve, Mahowald, Sleep Med 2013;14:744–748, DOI 10.1016/j.sleep.2012.10.009 (Europe PMC)
• Postuma et al., Brain 2019;142:744–759, DOI 10.1093/brain/awz030, PMID 30789229
• Not yet verified: the share of 2019 conversions that were Parkinson's (not in the abstract); the 1996 paper's full text. All numbers above were checked against the PubMed abstracts.