Grant supports study of sleep disorder linked to neurodegeneration

An international team of researchers led by the Washington University School of Medicine in St. Louis, Mayo Clinic in Rochester, Minnesota, and Montreal Neurological Institute-Hospital of McGill University received a five-year grant expected to total $35.1 million to develop biomarkers that indicate which people with rapid eye movement (REM) sleep behavior disorder will go on to develop neurodegenerative diseases, which specific diseases, when symptoms will arise, and how quickly the diseases will progress, according to an announcement earlier this month.

Patients with REM sleep behavior disorder act out their dreams. While sleeping safely in bed, for example, they might throw up their arms to catch an imaginary ball or try to run from an illusory assailant. Patients with the disorder have a 50 percent to 80 percent chance of developing a serious neurodegenerative disease within a decade of diagnosis.

The grant, from the National Institute on Aging (NIA) and the National Institute of Neurological Disorders and Stroke (NINDS), will help lay the groundwork for clinical trials focused on stopping the troublesome condition from progressing into a debilitating disease, researchers said.

REM sleep behavior disorder is linked to Parkinson’s disease, a movement condition; dementia with Lewy bodies, which causes cognitive decline; and multiple system atrophy, in which the ability to regulate involuntary functions such as blood pressure, breathing, and bladder and bowel function deteriorates.

Normally, people are paralyzed during REM sleep, the phase of sleep in which dreaming occurs. Acting out dreams is an early sign that something in the brain is not functioning quite as it should. REM sleep behavior disorder is connected to diseases caused by an accumulation of abnormal clumps of the protein alpha-synuclein in the brain. Such clumps often coalesce early in the course of the diseases in a part of the brain that paralyzes the body during REM sleep. As that area becomes damaged, people start thrashing around as they dream.

Several treatment strategies targeting alpha-synuclein are being developed and may become available for clinical trials in REM sleep behavior disorder. The researchers said they first need to identify a set of findings on specialized tests, or biomarkers, of impending neurological disease in people with REM sleep behavior disorder.

The study will follow about 430 participants with REM sleep behavior disorder and 60 people without sleep problems for five years. Patients and control participants will undergo regular comprehensive clinical exams and overnight sleep studies. They also will provide samples of blood and, if willing, cerebrospinal fluid. Participants with REM sleep behavior disorder also will undergo brain scans, the researchers said.

More than 2 million people in the U.S. are living with Lewy Body disorders, a group of diseases caused by clumps of alpha-synuclein in their brains. These so-called synucleinopathies include dementia with Lewy bodies, Parkinson’s disease, and multiple system atrophy. Collectively, they are the second most common kind of neurodegenerative diseases after Alzheimer’s disease.

Alzheimer’s disease and synucleinopathies share several similarities. In both, abnormal clumps of proteins accumulate in the brain for years prior to any symptom, with amyloid and tau in Alzheimer’s disease and synuclein in Lewy body disorders. About half of people with Alzheimer’s disease-related clumps of amyloid and tau also have clumps of synuclein, which is why synucleinopathies are included among the Alzheimer’s disease-related dementias. In addition, symptoms such as changes in thinking and behavior occur early in the disease process in both kinds of conditions.

Not all people with Lewy Body disorders have movement issues in their sleep prior to the onset of neurological symptoms. Studying people with REM sleep behavior disorder, at the earliest stages of a neurodegenerative process, may yield insight into how abnormal protein clumps lead to damage to the brain, how different symptoms arise, and how to stop or slow the neurodegenerative process.