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NEUROLOGY 1997;49:1513-1521
© 1997 American Academy of Neurology

Changes of hippocampal N-acetyl aspartate and volume in Alzheimer's disease

A proton MR spectroscopic imaging and MRI study

N. Schuff, PhD, D. Amend, PhD, F. Ezekiel, BA, S. K. Steinman, BSc, J. Tanabe, MD, D. Norman, MD, W. Jagust, MD, J. H. Kramer, MD, J. A. Mastrianni, MD, G. Fein, PhD and M. W. Weiner, MD

From the Magnetic Resonance Unit (Drs. Schuff, Amend, Tanabe, and Weiner, and S.K. Steinman), and Psychiatry Research (Dr. Fein and F. Ezekiel), Department of Veterans Affairs Medical Center, San Francisco, the Departments of Radiology (Drs. Schuff, Tanabe, Norman, Fein, and Weiner, and S.K. Steinman), Psychiatry (Drs. Kramer, Fein, and Weiner), and Neurology (Drs. Mastrianni and Weiner), University of California, San Francisco; the Center for Functional Imaging (Dr. Jagust), Lawrence Berkeley Laboratory, and the Department of Neurology (Dr. Jagust), University of California, Davis, CA.

Address correspondence and reprint requests to Dr. Norbert Schuff, DVA Medical Center, MR Unit, 4150 Clement Street, 114M, San Francisco, CA 94121.

Hippocampal atrophy detected by MRI is a prominent feature of early Alzheimer's disease (AD), but it is likely that MRI underestimates the degree of hippocampal neuron loss, because reactive gliosis attenuates atrophy. We tested the hypothesis that hippocampal N-acetyl aspartate (NAA; a neuronal marker) and volume used together provide greater discrimination between AD and normal elderly than does either measure alone. We used proton MR spectroscopic imaging (1H MRSI) and tissue segmented and volumetric MR images to measure atrophy-corrected hippocampal NAA and volumes in 12 AD patients (mild to moderate severity) and 17 control subjects of comparable age. In AD, atrophy-corrected NAA from the hippocampal region was reduced by 15.5% on the right and 16.2% on the left (both p<0.003), and hippocampal volumes were smaller by 20.1% (p<0.003) on the right and 21.8% (p <0.001) on the left when compared with control subjects. The NAA reductions and volume losses made independent contributions to the discrimination of AD patients from control subjects. When used separately, neither hippocampal NAA nor volume achieved to classify correctly AD patients better than 80%. When used together, however, the two measures correctly classified 90% of AD patients and 94% of control subjects. In conclusion, hippocampal NAA measured by 1H MRSI combined with quantitative measurements of hippocampal atrophy by MRI may improve diagnosis of AD.

Supported by NIH grant R01AG10897 (M.W.W), NIH grant AG10129 (W.J.), and NIH/NIA grant P01AG12435 (M.W.W.). Additional support is acknowledged from the DVA Medical Research Service (M.W.W.), a DVA Research Career Scientific Award (G.F.), and an Individual Research Service Award NIH AG05759-02(D.A.).

Received February 19, 1997. Accepted in final form July 9, 1997.




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