Does donepezil treatment slow the progression of hippocampal atrophy in patients with Alzheimer's disease?
OBJECTIVE
The only approved pharmacological approach for the symptomatic treatment of Alzheimer's disease in Japan is the use of a cholinesterase inhibitor, donepezil hydrochloride. Recent in vivo and in vitro studies raise the possibility that cholinesterase inhibitors can slow the progression of Alzheimer's disease. The purpose of the present study was to determine whether donepezil has a neuroprotective effect in Alzheimer's disease by using the rate of hippocampal atrophy as a surrogate marker of disease progression.


METHODS
In a prospective cohort study, 54 patients with Alzheimer's disease who received donepezil treatment and 93 control patients with Alzheimer's disease who never received anti-Alzheimer drugs underwent magnetic resonance imaging (MRI) twice at a 1-year interval. The annual rate of hippocampal atrophy of each subject was determined by using an MRI-based volumetric technique. Background characteristics, age, sex, disease duration, education, MRI interval, apolipoprotein E (APOE) genotype, and baseline Alzheimer's Disease Assessment Scale score were comparable between the treated and control groups.


RESULTS
The mean annual rate of hippocampal volume loss among the treated patients (mean=3.82%, SD=2.84%) was significantly smaller than that among the control patients (mean=5.04%, SD=2.54%). Upon analysis of covariance, where those confounding variables (age, sex, disease duration, education, MRI interval, APOE genotype, and baseline Alzheimer's Disease Assessment Scale score) were entered into the model as covariates, the effect of donepezil treatment on hippocampal atrophy remained significant.


CONCLUSIONS
Donepezil treatment slows the progression of hippocampal atrophy, suggesting a neuroprotective effect of donepezil in Alzheimer's disease.
Hashimoto
Mamoru
M
Hyogo Institute for Aging Brain and Cognitive Disorders, Hyogo, Japan. qq257xk9@minos.ocn.ne.jp
Kazui
Hiroaki
H
Matsumoto
Keiji
K
Nakano
Yoko
Y
Yasuda
Minoru
M
Mori
Etsuro
E
D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology*; D001057:Apolipoproteins E / Q000235:genetics; D001284:Atrophy; D002800:Cholinesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015331:Cohort Studies; D018450:Disease Progression; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005838:Genotype; D015577:Geriatric Assessment; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D007189:Indans / Q000494:pharmacology / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D013997:Time Factors; D016896:Treatment Outcome
D001057:Apolipoproteins E; D002800:Cholinesterase Inhibitors; D007189:Indans; D018696:Neuroprotective Agents; D010880:Piperidines; D000077265:Donepezil