Conversion from mild cognitive impairment to probable Alzheimer's disease predicted by brain magnetic resonance spectroscopy

Am J Psychiatry. 2005 Apr;162(4):667-75. doi: 10.1176/appi.ajp.162.4.667.


Objective: Mild cognitive impairment has been regarded as a pre-Alzheimer condition, but some patients do not develop dementia. Given the available therapies for Alzheimer's disease, early diagnosis is of paramount importance. The authors' objective was to determine whether findings from magnetic resonance spectroscopy (MRS) of the hippocampus and other cortical areas would predict conversion from amnestic mild cognitive impairment to probable Alzheimer's disease.

Method: A longitudinal inception cohort of 53 consecutive and incident subjects fulfilling the criteria of amnestic mild cognitive impairment was followed for a mean period of 3 years. At baseline, a neuropsychological examination (Mini-Mental State Examination, Blessed Dementia Rating Scale, Clinical Dementia Rating, verbal fluency test, and memory tests) and standard blood tests were performed, and three cortical areas were examined by proton MRS: left hippocampus, right parietal cortex, and left occipital cortex. The patients were evaluated periodically to detect conversion to probable Alzheimer's disease. The statistical analysis of predictions was based on receiver operating characteristic curves.

Results: By the follow-up assessment that occurred on average after 3 years, 29 patients (55%) had developed probable Alzheimer's disease. An occipital cortex N-acetylaspartate/creatine ratio < or =1.61 predicted dementia at 100% sensitivity and 75% specificity (area under the curve=0.91, 95% CI=0.80-0.97). The positive predictive value was 83%, and the negative predictive value was 100%, with an overall cross-validated classification accuracy of 88.7%. None of the values in the hippocampus and parietal cortex had significant predictive value.

Conclusions: MRS of the brain performed on patients with mild cognitive impairment is a valuable tool in predicting conversion to probable Alzheimer's disease. Occipital values were more reliable than hippocampal values in this prediction.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / metabolism
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / metabolism
  • Brain / metabolism*
  • Choline / metabolism
  • Cognition Disorders / diagnosis*
  • Cognition Disorders / metabolism
  • Cohort Studies
  • Creatine / metabolism
  • Female
  • Follow-Up Studies
  • Hippocampus / metabolism
  • Humans
  • Inositol / metabolism
  • Longitudinal Studies
  • Magnetic Resonance Spectroscopy / statistics & numerical data*
  • Male
  • Middle Aged
  • Occipital Lobe / metabolism
  • Probability
  • Severity of Illness Index


  • Aspartic Acid
  • Inositol
  • N-acetylaspartate
  • Creatine
  • Choline