Reduced Gray Matter Volume of the Thalamus and Hippocampal Region in Elderly Healthy Adults with no Impact of APOE ε4: A Longitudinal Voxel-Based Morphometry Study

Background: Many cross-sectional voxel-based morphometry (VBM) investigations have shown significant inverse correlations between chronological age and gray matter (GM) volume in several brain regions in healthy humans. However, few VBM studies have documentedGMdecrements in the healthy elderly with repeated MRI measurements obtained in the same subjects. Also, the extent to which the APOE epsilon 4 allele influences longitudinal findings of GM reduction in the healthy elderly is unclear. Objective: Verify whether regional GM changes are associated with significant decrements in cognitive performance taking in account the presence of the APOE epsilon 4 allele. Methods: Using structural MRI datasets acquired in 55 cognitively intact elderly subjects at two time-points separated by approximately three years, we searched for voxels showing significant GM reductions taking into account differences in APOE genotype. Results: We found global GM reductions as well as regional GM decrements in the right thalamus and left parahippocampal gyrus (p < 0.05, family-wise error corrected for multiple comparisons over the whole brain). These findings were not affected by APOE epsilon 4. Conclusions: Irrespective of APOE epsilon 4, longitudinal VBM analyses show that the hippocampal region and thalamus are critical sites where GM shrinkage is greater than the degree of global volume reduction in healthy elderly subjects.