The current application is based on the knowledge that sleep disorders and excessive daytime sleepiness (EDS) can affect about 75 percent of patients with Parkinson's disease (PD) and there is increasing evidence for sleep-arousal deficits and pronounced variations in attention and alertness in this population. Patients with Parkinson's disease dementia (PDD) often have sleep-disordered breathing (SDB). Patients with SDB also experience sleep fragmentation and become hypoxic during the night, which can result in daytime impairments including EDS and cognitive dysfunction. The state-of-the-art treatment for SDB is Continuous Positive Airway Pressure (CPAP). Many SDB patients successfully treated with CPAP show improvement in EDS and in memory and other cognitive functions. We have shown that treating SDB with CPAP in patients with Alzheimer's disease leads to improvement in sleep, in SDB and in cognition. The primary aim of this study is to examine the effect of CPAP treatment on sleep, daytime functioning and cognitive functioning in PDD patients with SDB. Exploratory or secondary aims include examining the relationship between SDB and other sleep disorders such as REM behavior disorder and restless legs syndrome and whether treatment of SDB will ameliorate the symptoms of these other sleep disorders. In addition, the effect of improving the patients'sleep on their study-partners will be examined. The study is designed as a randomized, double-blind, placebo-controlled trial of CPAP. As a comparison group, half the patients will first be randomly assigned to three weeks of sham CPAP, followed by three weeks of therapeutic CPAP treatment. Sleep, functional outcome and mood questionnaires and a repeatable neuropsychological test battery, chosen to be sensitive to the cognitive deficits associated with PDD, sleep apnea, and/or treatment with CPAP, will be administered before the start of treatment, after three weeks, and after six weeks of treatment. All tests will be repeated at three months and at six months to look for long-term improvement with CPAP. We hypothesize that cognitive deficits in PDD are a result of PD-pathology related deficits plus SDB related deficits. While CPAP is unlikely to improve deficits secondary to the PD-pathology, it should improve deficits secondary to the SDB-pathology. If a patient with PDD is functioning near the threshold of functional disability, even slight improvement, i.e., the extra burden added by the SDB, could be markedly important in terms of maintaining independent functioning. The long-term goal of this line of research is to find a new approach that might improve the quality of life, delay dementia, and reduce caregiver stress.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Special Emphasis Panel (ZRG1-RPHB-A (03))
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Mackiewicz, Miroslaw
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University of California San Diego
Schools of Medicine
La Jolla
United States
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