The effect of donepezil on sleep and REM sleep EEG in patients with Alzheimer disease: a double-blind placebo-controlled study.
OBJECTIVE
Examine the effects of donepezil on sleep and rapid eye movement (REM) sleep electroencephalogram (EEG) in patients with Alzheimer disease, using polysomnography, and the correlation between REM sleep EEG parameters and cognitive scores.


METHODS
Randomized, double-blind, placebo-controlled design.


METHODS
Two sleep research centers, University Hospital.


METHODS
Thirty-five patients with mild to moderate Alzheimer disease, allocated to 2 groups: donepezil treated (n=17) and placebo treated (n=18).


METHODS
Patients were administered donepezil or placebo.


METHODS
Polysomnography with REM sleep EEG spectral analysis and cognitive evaluation using the Alzheimer Disease Assessment Scale, cognitive subscale, were performed at baseline and after 3 and 6 months. Slowing ratio was the ratio between slow and fast EEG frequency bands. Cognitive and sleep data were analyzed using analysis of variance. Correlations between cognitive improvement and REM sleep EEG were also calculated.


RESULTS
REM sleep increased significantly after 3 and 6 months of donepezil treatment compared with baseline and placebo (p < .01). Overall theta (p = .04), frontal theta (p < .01) and frontal delta (p = .03) absolute power during REM sleep decreased after 6 months of donepezil treatment. The occipital slowing ratio decreased during treatment (p = .04). REM sleep overall and frontal and centroparietal alpha absolute power significantly correlated with the cognitive improvement rate on the Alzheimer Disease Assessment Scale, cognitive subscale (r = 0.75, r = 0.71, r = 0.78); p < .01).


CONCLUSIONS
Donepezil treatment enhanced REM sleep and reduced slow frequencies of REM sleep EEG, suggesting a possible action upon REM sleep-related cholinergic neurons in patients with Alzheimer disease. Furthermore, REM sleep alpha power may predict the cognitive response to donepezil.
Psychobiology Department, Universidade Federal de São Paulo, Brazil. waltermoraes@giro.com.br
Walterandré dos Santos
Wdos S
Moraes
Dalva Rollemberg
DR
Poyares
Christian
C
Guilleminault
Luiz Roberto
LR
Ramos
Paulo Henrique Ferreira
PH
Bertolucci
Sergio
S
Tufik
D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D000077265:Donepezil; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects*; D005260:Female; D006801:Humans; D007189:Indans / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use*; D017286:Polysomnography; D011594:Psychometrics; D012895:Sleep, REM / Q000187:drug effects*
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil