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Alzheimer Disease: Postmortem Neuropathologic Correlates of Antemortem ¹H MR Spectroscopy Metabolite Measurements¹

¹ From the Departments of Radiology (K.K., J.L.W., C.R.J.), Neurology (D.S.K., K.A.J., B.F.B., R.C.P.), Pathology and Laboratory Medicine (J.E.P.), and Health Sciences Research (S.D.W.), Mayo Clinic, 200 First St SW, Rochester, MN 55905; and Department of Pathology and Laboratory Medicine, Mayo Clinic, Jacksonville, Fla (D.W.D.). Received September 7, 2007; revision requested December 18; revision received December 28; final version accepted February 4, 2008. K.K. supported by Paul B. Beeson Career Development Award in Aging K23 AG030935 and Alzheimer's Association New Investigator Research grant 03-4842. Supported by National Institutes of Health Roadmap Multidisciplinary Clinical Research Career Development Award grants KL2 RR024151 (NIH/NCRR) (K.K., K.A.J.), P50 AG16574 (NIH/NIA) and U01 AG06786 (NIH/NIA) (R.C.P.), and R01 AG11378 (NIH/NIA) (C.R.J.), and the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program. Address correspondence to K.K. (e-mail: kantarci.kejal@mayo.edu).

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.

© RSNA, 2008