People with more slow wave sleep (i.e., deep sleep) had better cognitive performance in a study of 32 patients with Parkinson's disease, published this summer in the Journal of Parkinson's Disease by UAB researchers led by Amy Amara, M.D., Ph.D., associate professor in the Department of Neurology.
Amara and colleagues already have demonstrated that exercise can increase slow wave sleep in patients with Parkinson’s. An important next step is to identify patients who will benefit most. That is the subject of a new clinical trial led by Amara that is just starting to enroll patients.
Cognitive dysfunction affects up to 80% of patients with Parkinson's disease, impairing quality of life, increasing caregiver burden and increasing the risk of institutionalization, says Amara, who treats patients with Parkinson's disease in UAB's Movement Disorders Clinic and specializes in treatment of sleep disorders.
Parkinson’s and sleep
Slow wave sleep, commonly referred to as deep sleep, is thought to be the stage when memories are consolidated, and it is when sleepers are the hardest to awaken. "Increased slow wave sleep also is important for executive function," Amara said, including planning, problem-solving and working with others.
Slow wave sleep, commonly referred to as deep sleep, is thought to be the stage when memories are consolidated, and it is when sleepers are the hardest to awaken.
Sleep disorders and disturbances are very common in patients with Parkinson's disease — affecting anywhere from three-quarters to 98% of patients, according to various studies. In addition to sleep fragmentation, rapid eye movement sleep behavior disorder, daytime sleepiness and insomnia, patients with Parkinson's have altered sleep architecture, with reduced sleep efficiency (the percentage of time in bed that is actually spent asleep), lower total sleep time and less slow wave sleep, Amara explains. "In our Movement Disorders Clinic here at UAB, we always ask about sleep," she said.
Slow wave sleep in particular was associated with cognitive function in Amara’s recent study in the Journal of Parkinson’s Disease. There are medications that seem to increase slow wave sleep, she says. Unfortunately, the evidence for effectiveness is limited and available treatments can have detrimental side effects. "Whether medications that improve slow wave sleep might also increase cognition is unknown, but it would be an interesting question to study" Amara said.
No one has addressed that question, but Amara and other physicians already recommend one demonstrated way for their patients to improve sleep: exercise.
Parkinson’s and physical exercise
"Increased slow wave sleep also is important for executive function," Amara said, including planning, problem-solving and working with others.
In 2020, Amara and colleagues published the results of a randomized, controlled trial of exercise on objective and subjective sleep in Parkinson's disease in the journal Movement Disorders. All participants were 45 years or older with Parkinson's disease and none were in a regular exercise program. Half of the participants (27 people) were trained in resistance exercises (such as leg presses, knee extensions and lunges) and did supervised workouts three times a week for 16 weeks. The other half (28 people) were trained in sleep hygiene. The exercise group had significant improvements in sleep efficiency, total sleep time and slow wave sleep. "Exercise is an effective nonpharmacological intervention to improve this disabling nonmotor symptom [poor sleep]," Amara and her co-authors wrote. That paper was named the best research article published in the journal in 2019-20.
Previous studies had shown that exercise improves motor symptoms and subjective sleep quality in Parkinson's disease, but this was the first published study to evaluate the impact of exercise on objective sleep outcomes. "There's no real downside to prescribing exercise," Amara said. "It's just the trouble of getting people to do it. Adherence in our studies has been really high. But on the population level, people with Parkinson's disease in general have lower amounts of physical activity compared to healthy adults. They sometimes have balance problems, so they might be more reluctant to exercise for that reason and some people with Parkinson’s also have apathy due to the disease."
Amy Amara, M.D., Ph.D., specializes in treatment of sleep disorders and Parkinson's disease. Up to 98% of patients with Parkinson's experience sleep disturbances. "In our Movement Disorders Clinic here at UAB, we always ask about sleep," she said.
Several efforts to engage patients with Parkinson’s disease in exercise, including boxing-focused exercise, such as PD Fight Club or Rock Steady Boxing, have shown success, Amara said.
A personalized exercise prescription for Parkinson’s?
What is the best exercise prescription for individuals with Parkinson's? This is still an open question, but one that Amara is tackling in a new clinical trial that recently began enrolling patients. The project, funded by a major R01 grant from the National Institute of Child Health and Human Development, is titled Slow Wave Sleep as a Biomarker of Rehabilitation-Induced Cognitive Improvement in Parkinson's Disease.
Participants will be randomized to receive progressive resistance training immediately or to a delayed exercise control group, which will wait 12 weeks and then begin resistance training. Participants who respond to the resistance training with an increase in slow wave sleep will continue with the regimen through a second 12-week period. Participants who do not respond to the initial resistance training will transition to endurance training to assess if this can enhance their response.
Sleep disorders and disturbances are very common in patients with Parkinson's disease — affecting anywhere from three-quarters to 98% of patients, according to various studies.
The goal is to enroll three Parkinson's patients in the trial every month, for a total 120 participants during the five-year span of the grant. "It's a big undertaking," Amara said. “But we are excited to start answering this question of which prescription works for which patients.”
Glymphatic system and sleep
"Another really interesting thing we're going to study in this grant is whether there is more glymphatic clearance [after exercise]," Amara said. The glymphatic system is thought to remove waste from the brain and central nervous system. Two studies published in February 2021 showed that people with Parkinson’s disease have altered glymphatic drainage systems.
“The glymphatic system is thought to clear neurotoxins during sleep, although some people are not convinced," Amara said. "We will be looking at this with the R01 using specialized brain MRI techniques in participants before and after the exercise intervention.” One of the exploratory aims of the grant is to determine if exercise increases glymphatic clearance and if this predicts exercise-induced changes in cognition. If so, it could offer a way for physicians to identify the patients who would benefit most from exercise.
