Integrative assessment of brain atrophy in Alzheimer's disease: Parallel hippocampal and thalamic atrophy

In the past two decades, detailed descriptions of brain atrophy, which is the most characteristic imaging hallmark of Alzheimer's disease (AD), contributed to a better understanding of the pathogenesis of the disease. The present study aims to obtain both the global and regionally specific information about the AD-related degenerative process. A total of 12 AD subjects and 13 healthy controls were included in this study. Gross brain volume as well as total gray and white matter volume was evaluated by SIENAX. Localised gray matter atrophy was identified with optimised VBM approach (FSL-VBM). Subcortical atrophy was evaluated by active shape model implemented in FIRST analysis. SIENAX analysis displayed the total brain atrophy in AD patients. VBM analysis showed atrophy in the bilateral mediotemporal regions, as well as in posterior brain regions. Atrophy of the bilateral thalami and hippocampi was identified and also showed to be regionally specific. Vertex analysis of the segmented thalami and hippocampi indicated shrinking of the bilateral anterior thalami and the left medial hippocampus. Interestingly, the loss of thalamic volume was highly correlated to the hippocampal atrophy on both sides in AD patients, but not in healthy controls. An integrative approach in multilevel cortical and subcortical evaluation of the structural MRI data showed the pattern of both the global and local atrophy in AD patients compared to healthy controls. In addition to previous results, our study raises the issue of potentially independent atrophy of hippocampi and thalami. Obtaining the complex information about the volume and shape of subcortical structures, followed by the analysis of local changes, along with the global assessment of the neocortical atrophy, can help in the detailed interpretation of AD-related neurodegenerative process. Upper row: Boxplot of the Dice overlap crosses of the total brain, gray matter (GM) and white mattet (WM) volume difference between AD patients and healthy controls, showing significant AD-related brain atrophy. On the box-plot, the central mark is the mean, the boxes represent the 25% and 75% percentiles, and outliers are depicted as red crosses. The lower two rows: Boxplot of the Dice overlap of the hippocampal and thalamic volume difference between AD patients and healthy controls. Hippocampal and amygdalar volumes are represented on the right (R) and on the left (L). Parallel atrophy were significant for the bilateral thalami and hippocampi. A-B Vertex shape analysis comparison of the thalami (A) and hippocampi (B) between AD patients and healthy subjects. Focal atrophy (inward movement of vertices in the AD subjects is present on the antero-medio-ventral side of bilateral thalami (A) and medial side of the left hippocampus (B). The vertex difference results are colour-coded by F-statistic values (red-blue = low-high F) thresholded at p<0.05 uncorrected. Correlation of thalamic and hippocampal volumes. Volumes are represented in voxels. Areas of decreased gray matter thickness in AD patients when compared with the controls, depicted as local maximums of the significant clusters (P<0.05). Statistical images are overlaid on standard brain (MNI152).