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First published online on January 15, 2008
Chest, doi:10.1378/chest.07-1446
doi:10.1378/chest.07-1446
(Chest. 2008; 133:677-683)
© 2008 American College of Chest Physicians
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Donepezil Improves Obstructive Sleep Apnea in Alzheimer Disease*

A Double-Blind, Placebo-Controlled Study

Walter Moraes, MD, PhD; Dalva Poyares, MD, PhD; Lucia Sukys-Claudino, MD; Christian Guilleminault, MD, PhD and Sergio Tufik, MD, PhD

* From the Psychobiology Department (Drs. Moraes, Poyares, Sukys-Claudino, and Tufik), Universidade Federal de São Paulo, São Paulo, Brazil; and Human Sleep Research Center (Dr. Guilleminault), Department of Psychiatry and Behavioral Science, School of Medicine, Stanford University, Palo Alto, CA.

Correspondence to: Walter Moraes, MD, PhD, R. Manuel de Paiva, 313-São Paulo-SP, 04106-020, Brazil; e-mail: waltermoraes{at}giro.com.br

Abstract

Background: There is an association between Alzheimer disease and sleep-disordered breathing. Donepezil is the drug most frequently used to treat cognitive symptoms in Alzheimer disease. This study evaluates the effects of donepezil on obstructive sleep apnea in patients with Alzheimer disease.

Methods: Randomized, double-blind, placebo-controlled design. Twenty-three patients with mild-to-moderate Alzheimer disease and apnea-hypopnea index (AHI) > 5/h were allocated to two groups: donepezil treated (n = 11) and placebo treated (n = 12). Polysomnography and cognitive evaluation using Alzheimer disease assessment scale-cognitive (ADAS-cog) subscale were performed at baseline and after 3 months. Cognitive and sleep data were analyzed using analysis of variance.

Results: AHI and oxygen saturation improved significantly after donepezil treatment compared to baseline and placebo (p < 0.05). Rapid eye movement (REM) sleep duration increased after donepezil treatment (p < 0.05). ADAS-cog scores improved after donepezil treatment, although they did not correlate with REM sleep increase and sleep apnea improvement (p < 0.01).

Conclusions: Donepezil treatment improved AHI and oxygen saturation in patients with Alzheimer disease. Treatment also increased REM sleep duration and reduced ADAS-cog scores.

Trial registration: ClinicalTrials.gov Identifier: NCT00480870 [ClinicalTrials.gov] .

Key Words: Alzheimer • donepezil • oxygen saturation • polysomnography • rapid eye movement sleep • sleep apnea






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