A longitudinal study of gray matter volume decline with age and modifying factors.

The rate at which the volume of gray matter declines with normal aging, and whether gender or generational differences affect this rate, remain unclear. Using a longitudinal design over 6 years in 381 healthy community-dwelling individuals, we examined the rate of age-related loss in global gray matter volume, and how gender, generational and cerebrovascular risk factors affected this rate. We collected brain magnetic resonance images of the subjects, and calculated gray matter and intracranial volumes at baseline and follow-up using a fully automated technique. Using these volumes we then calculated the gray matter ratio (GMR), which measures gray matter volume as a percentage of the total intracranial volume. There were significant main effects of age, gender, and body mass index, and an age×gender interaction in the annual percentage change in the GMR (APC(GMR)). The APC(GMR) of younger women was lower than that in older women and men. Our results may help in understanding the mechanism(s) of normal brain aging, and in distinguishing neurodegenerative diseases from normal aging.