title: Acetylcholinesterase inhibitors and sleep architecture in patients with Alzheimer's disease.
abstract: 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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, University of California, San Diego, California, USA.
authors.forename: Jana R
authors.initials: JR
authors.lastname: Cooke
authors.forename: Jose S
authors.initials: JS
authors.lastname: Loredo
authors.forename: Lianqi
authors.initials: L
authors.lastname: Liu
authors.forename: Matthew
authors.initials: M
authors.lastname: Marler
authors.forename: Jody
authors.initials: J
authors.lastname: Corey-Bloom
authors.forename: Lavinia
authors.initials: L
authors.lastname: Fiorentino
authors.forename: Tamara
authors.initials: T
authors.lastname: Harrison
authors.forename: Sonia
authors.initials: S
authors.lastname: Ancoli-Israel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D002800:Cholinesterase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D000077265:Donepezil; D005260:Female; D005702:Galantamine / Q000627:therapeutic use; D006801:Humans; D007189:Indans / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D048448:Phenylcarbamates / Q000627:therapeutic use; D010880:Piperidines / Q000009:adverse effects* / Q000627:therapeutic use; D017286:Polysomnography; D000068836:Rivastigmine; D012894:Sleep Stages / Q000187:drug effects / Q000502:physiology; D012893:Sleep Wake Disorders / Q000139:chemically induced* / Q000503:physiopathology
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D048448:Phenylcarbamates; D010880:Piperidines; D005702:Galantamine; D000077265:Donepezil; D000068836:Rivastigmine