MR spectroscopy of brain white matter in the prediction of dementia

Background: Previous H-1-MR spectroscopy (MRS) studies compared biochemical spectra of persons with dementia with those of healthy control subjects. Given the long prodromal period of Alzheimer disease (AD), the authors sought to investigate whether biochemical changes can be observed also in the preclinical period. Methods: The authors prospectively followed 509 elderly persons (ages 60 to 90), who were free of clinical dementia at baseline, for on average 5.9 years. At baseline, H-1-MRS of the brain (1.5 T) was performed in a plane above the lateral ventricles that comprised mainly white matter voxels. Standard ratios of N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr) were calculated. Structural MRI was administered to assess white matter lesions and hippocampal atrophy. All persons were followed for incident dementia through repeated neuropsychological testing and linkage with medical records. Results: During follow-up, 37 persons developed dementia, of whom 27 fulfilled criteria for AD. Overall, biochemical ratios on H-1-MRS at baseline were not associated with the risk of incident dementia. However, people with higher Cho/Cr ratios had a higher risk to develop dementia or AD within 4 years (hazard ratio for dementia per SD increase 1.55 [95% CI 1.05 to 2.28]). This association attenuated and became nonsignificant after adjustment for white matter lesions on MRI. Conclusion: These data suggest that there are biochemical changes on H-1-MR spectroscopy of brains of persons with presymptomatic dementia.