The Effect of Apolipoprotein Polymorphism on Brain in Mild Cognitive Impairment: A Voxel-Based Morphometric Study

Abstract

We investigated the effect of apolipoprotein E (ApoE) on the whole brain in 51 individuals with mild cognitive impairment using voxel-based morphometry. Between cases heterozygous for the ApoE Ε4 (n = 15) and those who were ApoE Ε4 noncarriers (n = 28), only the right parahippocampal gyrus, with the entorhinal cortex included, reached the level of statistical significance. In cases homozygous for the Ε4 allele (n = 8) versus noncarriers, the greatest atrophy was located in the right amygdala followed by the right parahippocampal gyrus, the left amygdala and the left medial dorsal thalamic nucleus.

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

“…VBM provides an automated method to assess structural changes on a whole-brain level. The present study expands upon our previous work [6,7] by investigating differences in brain structure according to the APOE status and later conversion to dementia. We hypothesized that the APOE 4 carriers progressing to dementia would show more brain atrophy than the noncarriers.…”

“…Previous studies have detected MTL atrophy in relation to the APOE 4 allele in healthy controls, and MCI and AD subjects [3][4][5][6] . However, results are inconsistent as regards global brain atrophy as in a previous study, the 4 carriers did not show more global atrophy [3] .…”

“…Interestingly, the healthy 4 carriers have not presented greater global brain atrophy compared to noncarriers as assessed by visual rating [3] . Previously, a voxel-based morphometry (VBM) study showed that there is greater vulnerability in MCI 4 carriers in the medial temporal lobe (MTL) structures compared to noncarriers in a dose-dependent manner [6] .…”

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

“…3,4 Cross-sectional structural MR imaging studies indicated reduced gray matter in elderly APOE*E4 carriers including healthy controls, subjective memory impairment, mild cognitive impairment (MCI), and AD. [5][6][7][8][9][10][11][12][13][14] In MCI and AD, the APOE*E4-related GM decrease seems to affect areas involved in AD pathology, notably the hippocampus, amygdala, and mesial temporal cortex [14][15][16][17] but also the left occipital, frontal, and anterior cingulate cortices. 14,18 In healthy elderly controls, the APOE*E4 effect on brain structure is less clear.…”

ApoE ε4 Allele Related Alterations in Hippocampal Connectivity in Early Alzheimer’s Disease Support Memory Performance

“…Other findings are in line with this conclusion. There is a strong body of evidence suggesting that 4 carriers with MCI tend to have smaller hippocampi and amygdalae than patients not carrying the 4 allele but having similar demographic characteristics [57][58][59][60]. Other studies have instead reported volumetric loss in 4 carriers extending to other cortical and subcortical areas [61][62][63][64], although some have suggested that non-carriers can cope with a much more pronounced and extensive brain volume loss before manifesting the same level of cognitive disruption [64].…”