Magnified effects of the COMT gene on white-matter microstructure in very old age

Brain Struct Funct. 2015 Sep;220(5):2927-38. doi: 10.1007/s00429-014-0835-4. Epub 2014 Jul 24.


Genetic factors may partly account for between-person differences in brain integrity in old age. Evidence from human and animal studies suggests that the dopaminergic system is implicated in the modulation of white-matter integrity. We investigated whether a genetic variation in the Catechol-O-Methyltransferase (COMT) Val158Met polymorphism, which influences dopamine availability in prefrontal cortex, contributes to interindividual differences in white-matter microstructure, as measured with diffusion-tensor imaging. In a sample of older adults from a population-based study (60-87 years; n = 238), we found that the COMT polymorphism affects white-matter microstructure, indexed by fractional anisotropy and mean diffusivity, of several white-matter tracts in the oldest age group (81-87 years), although there were no reliable associations between COMT and white-matter microstructure in the two younger age groups (60-66 and 72-78 years). These findings extend previous observations of magnified genetic effects on cognition in old age to white-matter integrity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Distribution
  • Aged
  • Aged, 80 and over
  • Catechol O-Methyltransferase / genetics*
  • Cognition / physiology*
  • Diffusion Tensor Imaging / methods
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Prefrontal Cortex / metabolism*
  • White Matter / metabolism*


  • COMT protein, human
  • Catechol O-Methyltransferase