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From the Magnetic Resonance Unit (Drs. Chao, Schuff, Du, and Weiner), San Francisco Veterans Affairs Medical Center, CA; Departments of Radiology (Drs. Chao, Schuff, Du, and Weiner), Psychiatry (Drs. Chao, Kramer, Wolkowitz, Yaffe, and Weiner), Neurology (Drs. Miller, Yaffe, and Weiner), Epidemiology (Dr. Yaffe), and Medicine (Dr. Weiner), University of California, San Francisco; MRI Unit (Dr. Capizzano), Fernández Hospital, Buenos Aires, Argentina; Department of Psychiatry and Biobehavioral Science (Dr. O’Neill), University of California, Los Angeles; Neuroscience Institute (Dr. Jagust), University of California, Berkeley; and Department of Neurology (Dr. Chui), University of Southern California.
Address correspondence and reprint requests to Dr. Linda L. Chao, Assistant Adjunct Professor, VA Medical Center, 4150 Clement Street, 116R, San Francisco, CA 94121; e-mail: llchao{at}itsa.ucsf.edu
Background: N-acetylaspartate (NAA) in the medial temporal lobe (MTL) and parietal lobe gray matter (GM) is diminished in Alzheimer disease (AD). Because NAA is considered a marker of neuronal integrity, reduced medial temporal and parietal lobe NAA could be an early indication of dementia-related pathology in elderly individuals.
Objectives: 1) To determine whether cognitively impaired but nondemented (CIND) elderly individuals exhibit a similar pattern of reduced medial temporal and parietal lobe NAA as AD patients. 2) To compare regional NAA patterns, hippocampal and neocortical gray matter (GM) volumes in CIND patients who remained cognitively stable and those who became demented over 3.6 years of follow-up. 3) To examine the relationship between memory performance, medial temporal lobe NAA, and hippocampal volume.
Methods: Seventeen CIND, 24 AD, and 24 cognitively normal subjects were studied using MRSI and MRI.
Results: Relative to controls, CIND patients had reduced MTL NAA (19 to 21%, p = 0.005), hippocampal (11 to 14%, p 
0.04), and neocortical GM (5%, p = 0.05) volumes. CIND patients who later became demented had less MTL NAA (26%, p = 0.01), hippocampal (17 to 23%, p 0.05), and neocortical GM (13%, p = 0.02) volumes than controls, but there were no significant differences between stable CIND patients and controls. MTL NAA in combination with hippocampal volume improved discrimination of CIND and controls over hippocampal volume alone. In AD and CIND patients, decreased MTL NAA correlated significantly with impaired memory performance.
Conclusion: Reduced medial temporal lobe N-acetylaspartate, together with reduced hippocampal and neocortical gray matter volumes, may be early indications of dementia-related pathology in subjects at high risk for developing dementia.
Supported in part by NIH grants AG010897 and AG012435 and Veteran’s Affairs Research Service MIRECC and REAP.
Received February 24, 2004. Accepted in final form September 22, 2004.
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