The relationship between white matter brain metabolites and cognition in normal aging: the GENIE study

Brain Res. 2007 Aug 20;1164:108-16. doi: 10.1016/j.brainres.2007.06.027. Epub 2007 Jun 21.


Magnetic resonance spectroscopy (MRS) has demonstrated age-related changes in brain metabolites that may underlie micro-structural brain changes, but few studies have examined their relationship with cognitive decline. We performed a cross-sectional study of brain metabolism and cognitive function in 82 healthy adults (aged 50-90) participating in the GENIE (St GEorge's Neuropsychology and Imaging in the Elderly) study. Absolute metabolite concentrations were measured by proton chemical shift imaging within voxels placed in the centrum semiovale white matter. Cognitive abilities assessed were executive function, working memory, information processing speed, long-term memory and fluid intelligence. Correlations showed that all cognitive domains declined with age. Total creatine (tCr) concentration increased with age (r=0.495, p<0.001). Regression analyses were performed for each cognitive variable, including estimated intelligence and the metabolites, with age then added as a final step. A significant relationship was observed between tCr and executive function, long-term memory, and fluid intelligence, although these relationships did not remain significant after age was added as a final step in the regression. The regression analysis also demonstrated a significant relationship between N-acetylaspartate (NAA) and executive function. As there was no age-related decline in NAA, this argues against axonal loss with age; however the relationship between NAA and executive function independent of age and estimated intelligence is consistent with white matter axonal integrity having an important role in executive function in normal individuals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / physiology*
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / analysis
  • Aspartic Acid / metabolism
  • Brain / anatomy & histology
  • Brain / metabolism*
  • Cognition / physiology*
  • Cognition Disorders / etiology
  • Cognition Disorders / metabolism
  • Cognition Disorders / physiopathology
  • Cross-Sectional Studies
  • Female
  • Humans
  • Intelligence / physiology
  • Magnetic Resonance Imaging
  • Magnetic Resonance Spectroscopy
  • Male
  • Memory Disorders / metabolism
  • Memory Disorders / physiopathology
  • Middle Aged
  • Nerve Fibers, Myelinated / metabolism*
  • Neuropsychological Tests
  • Predictive Value of Tests
  • Wallerian Degeneration / diagnosis
  • Wallerian Degeneration / metabolism
  • Wallerian Degeneration / physiopathology


  • Aspartic Acid
  • N-acetylaspartate