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. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
2R01AG008415-16A2
Application #
7316555
Study Section
Special Emphasis Panel (ZRG1-RPHB-A (03))
Program Officer
Monjan, Andrew A
Project Start
1989-05-01
Project End
2012-08-31
Budget Start
2007-09-01
Budget End
2008-08-31
Support Year
16
Fiscal Year
2007
Total Cost
$292,965
Indirect Cost
Name
University of California San Diego
Department
Psychiatry
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Harmell, Alexandrea L; Neikrug, Ariel B; Palmer, Barton W et al. (2016) Obstructive Sleep Apnea and Cognition in Parkinson's disease. Sleep Med 21:28-34
Cauley, Jane A; Blackwell, Terri L; Redline, Susan et al. (2014) Hypoxia during sleep and the risk of falls and fractures in older men: the Osteoporotic Fractures in Men Sleep Study. J Am Geriatr Soc 62:1853-9
von Känel, Roland; Mausbach, Brent T; Mills, Paul J et al. (2014) Longitudinal relationship of low leisure satisfaction but not depressive symptoms with systemic low-grade inflammation in dementia caregivers. J Gerontol B Psychol Sci Soc Sci 69:397-407
Cooper, Denise C; Ziegler, Michael G; Milic, Milos S et al. (2014) Endothelial function and sleep: associations of flow-mediated dilation with perceived sleep quality and rapid eye movement (REM) sleep. J Sleep Res 23:84-93
Neikrug, Ariel B; Avanzino, Julie A; Liu, Lianqi et al. (2014) Parkinson's disease and REM sleep behavior disorder result in increased non-motor symptoms. Sleep Med 15:959-66
Neikrug, Ariel B; Liu, Lianqi; Avanzino, Julie A et al. (2014) Continuous positive airway pressure improves sleep and daytime sleepiness in patients with Parkinson disease and sleep apnea. Sleep 37:177-85
Ensrud, Kristine E; Parimi, Neeta; Fink, Howard A et al. (2014) Estimated GFR and risk of hip fracture in older men: comparison of associations using cystatin C and creatinine. Am J Kidney Dis 63:31-9
Maglione, Jeanne E; Ancoli-Israel, Sonia; Peters, Katherine W et al. (2014) Depressive symptoms and circadian activity rhythm disturbances in community-dwelling older women. Am J Geriatr Psychiatry 22:349-61
Spira, Adam P; Stone, Katie L; Rebok, George W et al. (2014) Sleep-disordered breathing and functional decline in older women. J Am Geriatr Soc 62:2040-6
Patterson, Ruth E; Emond, Jennifer A; Natarajan, Loki et al. (2014) Short sleep duration is associated with higher energy intake and expenditure among African-American and non-Hispanic white adults. J Nutr 144:461-6

Showing the most recent 10 out of 218 publications