Brain Atrophy in Mild Cognitive Impairment: MRI volumetric and voxel-based method study

Background: Mild cognitive impairment (MCI), a heterogeneous status, has gained increased interest from clinicians and researchers, because it has been shown to represent a transitional stage between normal ageing and very early Alzheimer’s disease (AD). Neuroimaging data, genetic findings, biological markers and neuropsychological tests have been evaluated as predictors of conversion from MCI into dementia, most commonly AD. Magnetic resonance imaging (MRI) using volumetric measurements of regions of interest (ROI), as well as more advanced imaging techniques, such as voxel based morphometry (VBM), increasingly used in studying AD patients, now were engaged in studying MCI subjects to determine which of them are to convert into dementia. Apolipoprotein E (APOE) allele ε4 is the most consistently confirmed genetic risk factor for Alzheimer’s disease (AD). Objectives: By using MRI volumetric studies to compare MCI subjects with controls and patients with mild AD, we intended to determine whether the entorhinal atrophy precedes hippocampal atrophy in AD. Moreover, with the help of VBM we wanted to map the gray matter loss in the entire brains of MCI subjects. As previous studies have suggested that the APOE genotype can influence the size of various brain structures, our objective was to investigate the difference in the morphologic expression of MCI in subjects carrying the APOE allele ε4 compared to the noncarriers using VBM. Finally we intended to conduct a follow-up study and determine the predictors for conversion into AD. Results: In the ROI-volumetric MRI study, we showed that the entorhinal volume loss predominated over the hippocampal volume loss in MCI, whereas more pronounced hippocampal volume loss appeared in mild AD. Using VBM in MCI subjects vs. controls, the greatest atrophy was found in the right hippocampus-amygdala region and in the right hippocampal tail and thalamus, while less extensive areas of atrophy were detected in the right superior temporal gyrus, the left thalamus, the left inferior temporal gyrus, and the left anterior cingulated gyrus. The extent of the atrophy was significant in the medial temporal lobe, on the right side. Between cases heterozygous for the APOE ε4 and those who were APOE ε4 noncarriers, only the right parahippocampal gyrus, with entorhinal cortex included, reached a level of statistical significance. In cases homozygous for the ε4 allele vs. 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. During the follow-up time of about 34 months, 21.7 % of the MCI subjects converted into dementia, with 15% developing AD. The right hippocampal and entorhinal volumes significantly predicted the conversion into AD. Conclusions: In the present study, the ERC atrophy appears to be dominant over the hippocampal atrophy in MCI, whereas more pronounced hippocampal atrophy was seen in mild AD. The VBM method revealed involvement of other brain areas, in addition to the MTL, in the state of MCI. The vast majority of the brain atrophy observed in individuals with MCI appears to be due to the small group homozygous for the ε4 allele. The atrophy of the MTL seen in the baseline, predicted the conversion to AD during a follow-up of 34 months, while the severity of cognitive impairment, the white matter lesions or the APOE provided no additional contribution to the prediction of conversion of MCI to AD. National Library of Medicine Classification: QU 470, QZ 180, WL 141, WL 314, WM 220, WN 185, WT 155 Medical Subject Headings: Alleles; Alzheimer Disease/physiopathology; Amygdala/pathology; Apolipoproteins E/genetics; Atrophy; Brain/pathology; Cognition Disorders/genetics; Dementia/ physiopathology; Entorhinal Cortex; Hippocampus/physiopathology; Magnetic Resonance Imaging/methods