Treatment with Aricept (donepezil) for six weeks does not seem to improve balance, either while standing or walking, for Parkinson’s patients with a minimal history of falls, according to results from a single-site Phase 2 trial.
The study, “Effects of augmenting cholinergic neurotransmission on balance in Parkinson’s Disease,” was published in the journal Parkinsonism and Related Disorders.
Motor and cognitive abilities depend on the coordinated interaction in the brain of two neurotransmitters — chemical substances that act as messengers and allow brain cells to communicate — called dopamine and acetylcholine.
In the brain of people with Parkinson’s, damage to neurons that produce dopamine and acetylcholine affect balance and gait. As the disease progresses, difficulties with such skills increase.
Impaired balance and gait impacts patients’ quality of life and risk falls. “Loss of mobility in the home and community affects tasks required for independent living and participation in family and community affairs. Falls cause minor to major trauma; the injuries restrict a person’s activities and add to the fear of falling which further reduces mobility,” the researchers wrote.
Aricept is a cholinesterase inhibitor that increases the levels of acetylcholine in the brain by preventing its breakdown. It is used to treat the symptoms of dementia caused by Alzheimer’s disease.
Researchers at Oregon Health & Science University hypothesized that measuring standing balance and dynamic (walking) balance, problems in both of which can cause falls, would allow them to assess if Aricept was of benefit to people with mild to moderately severe Parkinson’s disease.
Static balance is the ability to maintain postural stability and orientation with the body at rest, while dynamic balance is the ability to maintain postural stability and orientation while the body is in motion.
They designed a randomized, crossover Phase 2 trial (NCT02206620) in 49 Parkinson’s patients, mean age of 69. Participants were randomly assigned to a six-week treatment with Aricept, followed by a six-week treatment with placebo, or vice-versa, with six weeks of “washout” between each treatment. A washout period is the time in a clinical study during which a participant is taken off the investigative therapy, or other medication/placebo, so as to eliminate its effects on further treatment.
Oral capsules of Aricept were initially given at 5 milligrams (mg) a day, increasing to 10 mg a day after the first three weeks. Forty-five people completed the study; all had no or a limited fall history (could stand and walk unassisted for at least one minute) and reasonably healthy cognition.
The study’s main goal (endpoint) was to measure patients’ static and dynamic balance. Static balance was evaluated while they were standing with their feet together looking straight ahead at a fixed point with eyes open.
For dynamic balance assessments, participants were instructed to walk for two minutes at a comfortable pace up and down a 20-meter hallway.
As secondary goals researchers measured two parameters used as a readout of acetylcholine levels: the Attention Network Test, a 15-minute computerized test that measures attention and can determine whether changes in gait and balance are associated with changes in attention; and the Short Latency Afferent Inhibition (SAI), a transcranial magnetic stimulation method to evaluate cortical cholinergic activity.
Results showed that Aricept treatment had no effects on patients’ static and dynamic balance compared to the placebo. Secondary outcome measures of attention and SAI were also not significantly affected by treatment. Only one single parameter of static balance — postural sway — improved after treatment with donepezil.
“Contrary to our hypothesis, cholinergic augmentation with [Aricept] at 10 mg/day for 6 weeks did not affect measures of static or dynamic balance in people with PD,” the researchers wrote.
These results are in contrast with previous trials but a possible explanation, the researchers said, is the fact that “our participants may have had less impairment of cholinergic systems than the participants in the other studies.” Parkinson’s patients those studies, they added, all had an average history of at least one fall each week, and some had gait “freezing, indicating more advanced” disease.