Long-term use of REM sleep behavior disorder drug does not affect cognition

A research team led by Professor Yoon In-young from the Department of Psychiatry at Seoul National University Bundang Hospital (SNUBH) has published a study indicating that long-term use of clonazepam, a medication for isolated REM sleep behavior disorder, is not related to cognitive decline.

REM sleep behavior disorder is a condition characterized by violent behaviors, such as screaming and flailing of the arms and legs, during sleep. Normally, during REM sleep, the muscles are paralyzed and immobile; however, in REM sleep behavior disorder, this paralysis is absent, causing the person to act out their dreams physically.

Treatment typically involves clonazepam, a type of benzodiazepine medication, which is known to alleviate symptoms in most individuals. However, symptoms often reappear once the medication is discontinued, making long-term use of clonazepam common for managing the disorder.

However, individuals with REM sleep behavior disorder are at a heightened risk of developing neurodegenerative diseases such as Parkinson's disease and Lewy body dementia. Some reports have suggested that long-term use of benzodiazepine drugs, including clonazepam, may contribute to cognitive decline. This has raised significant concerns for patients with REM sleep behavior disorder who are required to take clonazepam over an extended period.

To investigate the association between cumulative clonazepam dosage and cognitive decline, the researchers followed 101 patients diagnosed with isolated REM sleep behavior disorder at the Sleep Center of SNUBH for an average of seven years.

The results indicated that patients with higher cumulative doses of clonazepam experienced a slight decline in memory and performance, both key components of cognitive function. To identify the factors contributing to this cognitive decline, the researchers analyzed the impact of various risk factors on cognitive function, including cumulative clonazepam dose, body mass index, smoking status, alcohol consumption, hypertension, and baseline cognitive function (assessed before starting treatment for REM sleep behavior disorder).

Among these factors, only baseline cognitive function in REM sleep behavior disorder patients was found to be associated with later cognitive decline. The cumulative clonazepam dose was not significantly linked to any domain of cognitive function, including memory, visuospatial function, performance, or global cognition. This suggests that baseline cognitive function is more crucial in cognitive decline than the cumulative dose of clonazepam.

"This is the first study to identify the relationship between cumulative clonazepam dose and cognitive decline in patients with isolated REM sleep behavior disorder," said Professor Yoon. "Since long-term use of medication for REM sleep behavior disorder does not significantly impact cognitive decline, it is recommended that patients with suspected REM sleep behavior disorder be diagnosed early and take the medication consistently to achieve good treatment outcomes."

The study results were published in the Journal of Clinical Sleep Medicine.