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Acetylcholinesterase Inhibitors and Sleep Architecture in Patients with Alzheimer’s Disease


Background and objective

Studies suggest that some acetylcholinesterase inhibitors (AChEIs) increase rapid eye movement (REM) sleep and nightmares in patients with Alzheimer’s disease (AD) but few have studied their effect on other sleep parameters. The objective of this study was to examine differences in sleep architecture in AD patients taking different AChEIs.


76 participants (51 men, 25 women) [mean age = 78.2 years; SD = 7.7] with mild to moderate AD underwent medication history screening as well as polysomnography to determine the percentage of each sleep stage. Participants were divided into groups based on AChEI used: donepezil (n = 41), galantamine (n = 15), rivastigmine (n = 8) or no AChEI (n = 12). General univariate linear model analyses were performed.


AChEI therapy had a significant effect on the percentage of stage 1 (p = 0.01) and stage 2 (p = 0.03) sleep. Patients in the donepezil group had a significantly lower percentage of stage 1 sleep than patients in the galantamine group (mean = 17.3%, SD = 11.7 vs 29.2%, SD = 15.0, respectively; p = 0.01), but there was no significant difference between the donepezil group and the rivastigmine (mean = 25.0%, SD = 12.3) or no AChEI groups (mean = 27.6%, SD = 17.7) in this respect. No significant differences in percentage of stage 1 between other groups were seen. Patients in the donepezil group also had a significantly higher percentage of stage 2 sleep than patients in the no AChEI group (mean = 63.6%, SD = 14.4 vs 51.4%, SD = 16.9, respectively; p = 0.04), but there was no significant difference between the donepezil group and either the galantamine group (mean = 56.5%, SD = 8.7) or the rivastigmine group (mean = 59.9%, SD = 8.4). There were no significant differences between groups in terms of percentage REM sleep or other sleep parameters.


Subgroups of AD patients (classified according to AChEI treatment) in this study differed with respect to the amount of stage 1 and stage 2 sleep experienced, with the donepezil-treated group having the lowest percentage of stage 1 sleep and the highest percentage of stage 2 sleep. There was no significant difference in the amount of REM sleep between the groups. Our data suggest that sleep architecture may be affected by the use of donepezil in patients with AD. Although not elicited in this study because of the small sample size, there may be a class effect of AChEIs on sleep architecture. Double-blind, placebo-controlled studies are needed to better understand causality and the effect of each AChEI on sleep architecture in patients with AD.

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  1. A ‘first-night effect’ refers to the disrupted or abnormal sleep architecture (manifested as an increased percentage of stage 1 sleep with resultant decreases in the other sleep stages) commonly seen on the first night of in-laboratory sleep recordings. Typically, the patient adapts to the laboratory setting on the second night of recordings.


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The authors would like to thank Deborah Greenfield for participant recruitment and data collection. This study was supported by grants from the National Institute of Aging (NIA AG08415, NIA P50 AG05131) and the National Institutes of Health (NIH M01 RR008270) and by the Research Service of the Veterans Affairs San Diego Healthcare System. The authors have no conflicts of interest that are directly relevant to the content of this manuscript.

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Correspondence to Sonia Ancoli-Israel.

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Cooke, J.R., Loredo, J.S., Liu, L. et al. Acetylcholinesterase Inhibitors and Sleep Architecture in Patients with Alzheimer’s Disease. Drugs Aging 23, 503–511 (2006).

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  • Rivastigmine
  • Galantamine
  • Sleep Architecture
  • Percentage Stage
  • Periodic Limb Movement Index