Alzheimer disease: postmortem neuropathologic correlates of antemortem 1H MR spectroscopy metabolite measurements.
OBJECTIVE
To determine the neuropathologic correlates of antemortem hydrogen 1 ((1)H) magnetic resonance (MR) spectroscopy metabolite measurements in subjects with Alzheimer disease (AD)-type pathology.


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 (1)H 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 (1)H 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 (1)H 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(N)(2) = 0.47, P < .001).


CONCLUSIONS
Antemortem (1)H MR spectroscopy metabolite changes correlated with AD-type pathology seen at autopsy. The study findings validated (1)H MR spectroscopy metabolite measurements against the neuropathologic criteria for AD, and when combined with prior longitudinal (1)H MR spectroscopy findings, indicate that these measurements could be used as biomarkers for disease progression in clinical trials.
Kantarci
Kejal
K
Departments of Radiology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA. kantarci.kejal@mayo.edu
Knopman
David S
DS
Dickson
Dennis W
DW
Parisi
Joseph E
JE
Whitwell
Jennifer L
JL
Weigand
Stephen D
SD
Josephs
Keith A
KA
Boeve
Bradley F
BF
Petersen
Ronald C
RC
Jack
Clifford R
CR
D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis*; D001921:Brain / Q000378:metabolism*; D003933:Diagnosis; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D011522:Protons; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013223:Statistics as Topic
D015415:Biomarkers; D011522:Protons