Age and gender effects on human brain anatomy: A voxel-based morphometric study in healthy elderly

The adult human brain shrinks slowly with age, but the regional specificity and tissue class specificity of this loss is unclear. Subjects (n = 122) were healthy aged participants in a longitudinal cohort who undergo periodic standardized cognitive and clinical examination. Multi-spectral segmentation of magnetic resonance images into grey matter (GM), white matter (WM) and CSF was performed on cross-sectional image data using a custom template and calculated prior probability maps. Global differences were evaluated by fitting a regression model for absolute and normalized subject GM, WM, and CSF values. Global and regional patterns of GM, WM and CSF differences were assessed using optimized voxel-based morphometry (VBM). GM volume decreased with age at a rate of 2.4 cm³/year (-0.18%/year); CSF increased by 2.5 cm³/year (0.20%/year). Regression analyses showed no significant decrease in WM volume, but a focal WM decrease with age was detected in the anterior corpus callosum using VBM. Diffuse reductions of GM volume were seen with age in the frontal, parietal, and temporal cortex, cerebellum and basal ganglia. Relative regional differences in cortical GM volume with age occurred in the frontal, parietal and temporal lobes, but not in medial temporal lobe or in posterior cingulate. We did not observe significant gender effects. These findings establish a baseline for comparison with pathologic changes in human brain volume between ages 58 and 95 years.