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

Charles D. Smith, Himachandra Chebrolu, David R. Wekstein, Frederick A. Schmitt, William R. Markesbery

Research output: Contribution to journalArticlepeer-review

279 Scopus citations


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.

Original languageEnglish
Pages (from-to)1075-1087
Number of pages13
JournalNeurobiology of Aging
Issue number7
StatePublished - Jul 2007

Bibliographical note

Funding Information:
This study was supported by NIA grant P50-AG05144 and GCRC grant M01 RR 02602. We thank MRI technicians, Robin Green and Agnes Bognar, who assisted in acquiring the scans and Dr. Peter Hardy for providing valuable technical assistance for this study.


  • Aging
  • Cortex
  • Magnetic resonance imaging
  • Volumetry

ASJC Scopus subject areas

  • Neuroscience (all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology


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