Alzheimer disease: Postmortem neuropathologic correlates of antemortem ¹H MR spectroscopy metabolite measurements

Purpose: To determine the neuropathologic correlates of antemortem hydrogen 1 (¹H) magnetic resonance (MR) spectroscopy metabolite measurements in subjects with Alzheimer disease (AD)-type pathology. Materials and Methods: This study was approved by the institutional review board and was compliant with HIPAA regulations. Informed consent was obtained from each subject. The authors identified 54 subjects who underwent antemortem ¹H MR spectroscopy and were clinically healthy or had AD-type pathology with low to high likelihood of AD according to National Institute on Aging-Reagan neuropathologic criteria at autopsy. They investigated the associations between ¹H MR spectroscopy metabolite measurements and Braak neurofibrillary tangle stage (Braak stage), neuritic plaque score, and AD likelihood, with adjustments for subject age, subject sex, and time between ¹H MR spectroscopy and death. Results: Decreases in N-acetylaspartate-to-creatine ratio, an index of neuronal integrity, and increases in myo-inositol-to-creatine ratio were associated with higher Braak stage, higher neuritic plaque score, and greater likelihood of AD. The N-acetylaspartate-to-myo-inositol ratio proved to be the strongest predictor of the pathologic likelihood of AD. The strongest association observed was that between N-acetylaspartate-to-myo-inositol ratio and Braak stage (R_N² = 0.47, P < .001). Conclusion: Antemortem ¹H MR spectroscopy metabolite changes correlated with AD-type pathology seen at autopsy. The study findings validated ¹H MR spectroscopy metabolite measurements against the neuropathologic criteria for AD, and when combined with prior longitudinal ¹H MR spectroscopy findings, indicate that these measurements could be used as biomarkers for disease progression in clinical trials.