Decline in prefrontal catecholamine synthesis explains age-related changes in cognitive speed beyond regional grey matter atrophy

Eur J Nucl Med Mol Imaging. 2012 Sep;39(9):1462-6. doi: 10.1007/s00259-012-2162-4. Epub 2012 Jun 19.


Purpose: Age-related decline in cognitive speed has been associated with prefrontal dopamine D1 receptor availability, but the contribution of presynaptic dopamine and noradrenaline innervation to age-related changes in cognition is unknown.

Methods: In a group of 16 healthy participants aged 22-61 years, we used PET and the radioligand FDOPA to measure catecholamine synthesis capacity (K (in) (app); millilitres per gram per minute) and the digit symbol substitution test to measure cognitive speed, a component of fluid IQ.

Results: Cognitive speed was associated with the magnitude of K (in) (app) in the prefrontal cortex (p < 0.0005). Both cognitive speed (p = 0.003) and FDOPA K (in) (app) (p < 0.0005) declined with age, both in a standard voxel-wise analysis and in a volume-of-interest analysis with partial volume correction, and the correlation between cognitive speed and K (in) (app) remained significant beyond the effects of age (p = 0.047). MR-based segmentation revealed that these age-related declines were not attributable to age-related alterations in grey matter density.

Conclusion: Our findings indicate that age-related changes in the capacity of the prefrontal cortex to synthesize catecholamines, irrespective of cortical atrophy, may underlie age-related decline in cognitive speed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aging / metabolism*
  • Aging / physiology
  • Atrophy / metabolism
  • Atrophy / physiopathology
  • Cognition / physiology*
  • Dopamine / biosynthesis*
  • Humans
  • Male
  • Middle Aged
  • Prefrontal Cortex / metabolism*
  • Prefrontal Cortex / pathology*
  • Prefrontal Cortex / physiology
  • Time Factors
  • Young Adult


  • Dopamine