Early sleep problems predict Parkinson’s

“The groundwork for future of Parkinson’s therapies is now being laid. And this enormous study represents an important step forward towards what will become preventative therapies for Parkinson’s. Future generations will hopefully not be affected by the condition as we can pick it up and treat it before it becomes debilitating. The study also has important implications for future clinical trial design, providing guidance on the size of cohorts and the criteria for inclusion/exclusion. This was a very impressive report.”

The so called “prodromal” period of Parkinson’s, during which some signs and symptoms may be evident but the full impact of the disease has not yet manifested, is receiving much attention by clinicians and researchers. Picking up subtle changes early on is essential for patients, as it can speed up access to treatments, and can yield important insights into the underlying mechanism of Parkinson’s. It also helps recruit people into neuroprotective trials for therapies with the potential for disease modification. The rationale is simple: the earlier we pick up changes in the brain, the sooner we can intervene and test whether therapies have the potential to arrest the disease in its earliest stage and before it becomes too extensive.

Although there are a number of candidate symptoms and signs that have been flagged as potentially important, these are not definitive predictors. Many people with one or some of these indicators will not go on to develop Parkinson’s. One of the exceptions is REM behaviour sleep disorder, known as RBD, which disturbs the brain mechanisms normally causing paralysis during REM sleep and results in “acting out” dreams. Individual RBD clinical centres have found that many people with RBD will go on to develop some form of neurodegenerative condition, including Parkinson’s and dementia.

This international collaborative effort, the largest of its kind, brought together 24 centres from Europe, the US and Canada, Australia and Korea to form the International RBD study group. A total of 1280 people with confirmed RBD underwent extensive baseline testing to assess their motor and mental function, sense of smell, blood pressure, urinary function and constipation, as well as anxiety and depression among other variables. They also underwent brain imaging (a DAT scan) to assess the degree of dopaminergic cell loss. None of these individuals had another diagnosis of a neurodegenerative condition, but they were all followed up over several years to assess when and what proportion might subsequently exhibit symptoms of parkinsonism or dementia.

The study found that after 12.5 years, 73.5% of these individuals had a diagnosis of either parkinsonsism or dementia. Other factors that increased the risk of developing a neurodegenerative condition were abnormal movement-related signs and symptoms, disturbed sense of smell, mild cognitive impairment, abnormal DAT scan, erectile dysfunction, colour vision problems, constipation, abnormal muscle tone during REM sleep and age.    

Based on these findings, the researchers were able to calculate that the sample size required for a future clinical trial of a disease modifying therapy was 366 on the treatment arm and 366 on a placebo: in other words, they were able to estimate how many participants should a trial have in order to definitively test whether a drug is successful in halving the rate of progression to parkinsonism or dementia. Adding other variables such as disturbed sense of smell and abnormal movement more than halved these numbers down to 157 patients per group.

To implement these findings, along with the group size calculations, into upcoming trials for disease modifying therapies for Parkinson’s.

• https://www.parkinsonsmovement.com/alpha-synuclein-roadmap/
• https://www.parkinsonsmovement.com/metabolic-syndrome/
• https://www.parkinsonsmovement.com/prion-like-spread/