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Neurology 2002;58:928-935
© 2002 American Academy of Neurology

Selective reduction of N-acetylaspartate in medial temporal and parietal lobes in AD

N. Schuff, PhD, A. A. Capizzano, MD, A. T. Du, MD, D. L. Amend, PhD, J. O’Neill, PhD, D. Norman, MD, J. Kramer, PhD, W. Jagust, MD, B. Miller, MD, O. M. Wolkowitz, MD, K. Yaffe, MD and M. W. Weiner, MD

From the Magnetic Resonance Unit (Drs. Schuff, Du, Amend, and Weiner), DVA Medical Center San Francisco; Departments of Radiology (Drs. Norman and Weiner), Neurology (Drs. Miller, Yaffe, and Weiner), Medicine (Dr. Weiner), and Psychiatry (Dr. Wolkowitz), University of California, San Francisco; MRI Unit (Dr. Capizzano), Fernández Hospital, Buenos Aires, Argentina; Department of Radiology (Dr. O’Neill), University of California, Los Angeles; and Department of Neurology (Dr. Jagust), University of California, Davis.

Address correspondence and reprint requests to Dr. Norbert Schuff, DVA Medical Center, 4150 Clement St. 114M, San Francisco, CA 94121; e-mail: nschuff{at}itsa.ucsf.edu

Background: Both AD and normal aging cause brain atrophy, limiting the ability of MRI to distinguish between AD and age-related brain tissue loss. MRS imaging (MRSI) measures the neuronal marker N-acetylaspartate (NAA), which could help assess brain change in AD and aging.

Objectives: To determine the effects of AD on concentrations of NAA, and choline- and creatine-containing compounds in different brain regions and to assess the extent NAA in combination with volume measurements by MRI improves discrimination between AD patients and cognitively normal subjects. Methods: Fifty-six patients with AD (mean age: 75.6 ± 8.0 years) and 54 cognitively normal subjects (mean age: 74.3 ± 8.1 years) were studied using MRSI and MRI.

Results: NAA concentration was less in patients with AD compared with healthy subjects by 21% (p < 0.0001) in the medial temporal lobe and by 13% to 18% (p < 0.003) in parietal lobe gray matter (GM), but was not changed significantly in white matter and frontal lobe GM. In addition to lower NAA, AD patients had 29% smaller hippocampi and 11% less cortical GM than healthy subjects. Classification of AD and healthy subjects increased significantly from 89% accuracy using hippocampal volume alone to 95% accuracy using hippocampal volume and NAA together.

Conclusion: In addition to brain atrophy, NAA reductions occur in regions that are predominantly impacted by AD pathology.




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