Abstract
IntroductionThe aim of this investigation was to assess the effect of galantamine, an acetylcholinesterase inhibitor and allosteric modulator of nicotinic receptors, on brain atrophy in individuals with mild cognitive impairment (MCI), and to assess effect modification by apolipoprotein E (APOE) genotype.MethodsWe used data from the Galantamine-International-11 (Gal-Int-11) trial, a 24-month, randomized, double blind, placebo-controlled, flexible-dose (16 to 24 mg daily) study in patients with MCI. Brain magnetic resonance imaging (MRI), including a 3-dimensional T1-weighted gradient echo volumetric sequence, was performed at screening and at 24 months. We recorded whole brain and hippocampal volumes, and calculated annual atrophy rates. Linear regression analysis was used to calculate adjusted mean differences in the rate of whole brain and hippocampal atrophy, between MCI patients treated with galantamine and with placebo. Additionally, we performed stratified analyses according to APOE genotype.ResultsData from 364 MCI patients with 24-month MRI data (galantamine, n = 176; placebo, n = 188) were included in the volumetric analysis. Subjects treated with galantamine demonstrated a lower rate of whole brain atrophy compared to those treated with placebo (adjusted mean difference 0.18% per year (95% confidence interval (CI) 0.04; 0.30)). Stratified analyses according to APOE genotype, showed that this effect was confined to patients who carried an APOE ϵ4 allele (adjusted mean difference 0.28% per year (95% CI 0.07; 0.50)). Rates of hippocampal atrophy did not differ significantly between study groups.ConclusionsPatients with MCI who were treated with galantamine demonstrated a lower rate of whole brain atrophy, but not of hippocampal atrophy, over a 24-month treatment period, compared to those treated with placebo. This protective effect of galantamine on whole brain atrophy rate in MCI was only present in APOE ϵ4 carriers.
Highlights
The aim of this investigation was to assess the effect of galantamine, an acetylcholinesterase inhibitor and allosteric modulator of nicotinic receptors, on brain atrophy in individuals with mild cognitive impairment (MCI), and to assess effect modification by apolipoprotein E (APOE) genotype
Older age was associated with higher whole brain atrophy rate (β per year increase, 0.02%) and higher hippocampal atrophy rate (β per year increase, 0.05%)
In a subset of MCI patients who participated in the Gal-Int-11 trial and underwent Magnetic resonance imaging (MRI) at baseline and at 24 months, we found that MCI patients who received galantamine showed lower whole brain atrophy rates compared with those treated with placebo
Summary
The aim of this investigation was to assess the effect of galantamine, an acetylcholinesterase inhibitor and allosteric modulator of nicotinic receptors, on brain atrophy in individuals with mild cognitive impairment (MCI), and to assess effect modification by apolipoprotein E (APOE) genotype. Patients with MCI have an increased risk for the development of Alzheimer’s disease (AD), with up to 15% of these patients progressing to dementia per year, compared with up to 2% of the normal older population [2,3]. Magnetic resonance imaging (MRI) has contributed to our understanding of the brain changes associated with MCI and AD. The degree and rate of medial temporal lobe and brain atrophy in individuals with MCI is greater than that in normal controls, and less than that in patients with AD [4]. In MCI subjects a lower brain or hippocampal volume or a higher rate of brain or hippocampal atrophy is predictive of progression of MCI to AD [7,8,9]
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