An MRI substudy of a donepezil clinical trial in mild cognitive impairment

• Published in: Neurobiology of aging Vol. 32; no. 12; pp. 2318.e31 - 2318.e41
• Main Authors: Schuff, Norbert, Suhy, Joyce, Goldman, Robert, Xu, Yikang, Sun, Yijun, Truran-Sacrey, Diana, Murthy, Anita
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2011
• Subjects: Aged; Aged, 80 and over; Amnestic MCI; Atrophy; Brain - drug effects; Brain - pathology; Cognitive decline; Cognitive Dysfunction - diagnosis; Cognitive Dysfunction - drug therapy; Cognitive Dysfunction - psychology; Donepezil; Double-Blind Method; Female; Hippocampus; Humans; Indans - pharmacology; Indans - therapeutic use; Internal Medicine; Magnetic Resonance Imaging - methods; Male; Middle Aged; Neurology; Piperidines - pharmacology; Piperidines - therapeutic use; Randomized clinical trial; Serial MRI volumetric imaging; Single-Blind Method; Surrogate marker; Whole brain analysis; Cognitive decline; Atrophy; Amnestic MCI; Randomized clinical trial; Donepezil; Surrogate marker; Whole brain analysis; Hippocampus; Serial MRI volumetric imaging
• ISSN: 0197-4580; 1558-1497; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2010.04.005

A magnetic resonance imaging (MRI) study was conducted as part of an intervention study in subjects with amnestic mild cognitive impairment (aMCI) to assess donepezil's treatment effect on brain atrophy. Adults with aMCI were randomly assigned to double-blind treatment with 10 mg/day donepezil hydrochloride or placebo for 48 weeks. Brain MRI scans were acquired at baseline and endpoint. The primary outcome measure was annualized percentage change (APC) in hippocampal volume; the main secondary outcome measure was APC in whole brain volumes. An analysis of variance (ANOVA) model including terms for treatment, site, and age was used to compare the treatment groups. APCs for hippocampal volumes were not significantly different between treatment groups. There were significant differences favoring the donepezil group for total ( p = 0.001), ventricular region ( p = 0.0002), and cortical region ( p = 0.003) whole brain volumes. Although the primary MRI outcome measure was negative, the main secondary MRI outcome measure showed a positive result. These findings suggest a treatment effect of donepezil on brain atrophy in aMCI.