Apolipoprotein E ε4 Allele Is Associated with Increased Atrophy in Progressive Mild Cognitive Impairment: A Voxel-Based Morphometric Study

Abstract

Background: The apolipoprotein E (APOE) Ε4 allele is a risk factor for Alzheimer’s disease. Earlier studies have shown differences in brain structure according to the APOE Ε4 status. Objective: To assess possible differences in brain structure according to the APOE Ε4 status in mild cognitive impairment (MCI) subjects in relation to conversion to dementia. Methods: In a follow-up study of 56 MCI subjects, 13 MCI subjects progressed to dementia (PMCI) during a mean follow-up time of 31 months. Brain structure differences in both stable MCI (SMCI) and PMCI Ε4 carriers and noncarriers in the baseline MRI scan were assessed with voxel-based morphometry. Results: The SMCI Ε4 carriers had atrophy in the amygdala and hippocampus compared to the SMCI noncarriers. The PMCI Ε4 carriers revealed atrophy of the left inferior frontal gyrus and parietal cortex compared to the PMCI noncarriers. Conclusion: The rate of brain atrophy in certain brain areas may be increased in Ε4-positive MCI subjects progressing to dementia.

The Neuroanatomical Substrate of Lexical-Semantic Decline in MCI APOE ε4 Carriers and Noncarriers

“…Significant differences especially in the hippocampus have been found and those which have assessed progression have reported accelerated atrophy in APOE e4 carriers, taking place primarily in the hippocampus. [53][54][55][56][57] One study more specifically reported greater atrophy in amygdala, parahippocampal gyrus, and in the medial dorsal nucleus of the thalamus but only in homozygous MCI APOE e4 carriers. 58 The present morphometric study is the first to focus on the preclinical MCI stage of AD, to include healthy noncarriers and to examine the link between the added neuropathological burden of APOE e4 and degraded lexical-semantic skills.…”

Apolipoprotein E Polymorphism and Brain Morphology in Mild Cognitive Impairment

“…The potential relevance of the ApoE genotype in the course of AD has been underlined by a recent longitudinal VBM study in mild cognitive impairment, which revealed higher baseline atrophy in 4 allele carriers and, even to a greater extent, in those 4-allele-positive individuals who had developed manifest AD at observed follow-up [24] .…”

APOE*E4Is Associated with Gray Matter Loss in the Posterior Cingulate Cortex in Healthy Elderly Controls Subsequently Developing Subtle Cognitive Decline

“…20 Longitudinal studies also indicated that among MCI converters, those with a positive APOE*E4 status displayed increased GM atrophy in AD-related brain regions. 24,25 The current investigation goes 1 step earlier in the degenerative process and assesses the effect of APOE allele status in healthy controls who subsequently developed subtle cognitive decline. To this end, we performed MR imaging and cognitive assessment at baseline in 382 community-dwelling elderly controls.…”