The long term goal of this project is to detect, diagnose, and monitor progression of Alzheimer's disease (AD). This project has studied 176 AD subjects and developed multislice 1H MRSI (TE=30) which measures N-acetyl aspartate (MAA), myo-inositol, and other metabolites in surface cortex and hippocampus. This will be used with segmented/volumed MRI, genetic and neuropsychological tests. Subjects (from the UCSF and the Northern California Alzheimer s Center) will include: AD (N=220), Frontotemporal Dementia (n=50), non-demented subjects with a Clinical Dementia Rating of 0.5 (n-100), and age matched Controls (n=140). Subjects will be followed to autopsy. Hypotheses: 1) Regional metabolic changes: The greatest antemortem changes of MRS-detectable metabolites (especially NAA and myo-inositol) occur in the hippocampus and in temporoparietal cortex in AD. 2) Anatomical- neuropsychological correlations: Neuron loss and other metabolite change (detected by MRSI) in specific brain regions is associated with specific types of cognitive impairment. 3) Diagnosis of AD: 1H MRSI and MRI, together with clinical measures provide more sensitive and specific diagnosis of AD than do MRI and clinical measures alone. 4) Diagnosis of Frontotemporal dementia (FTD): FTD is associated with both decreased NAA in the frontal lobes and genetic mutation in 17q21-22, and can be reliably distinguished from AD. Finally, a pilot study will be performed to determine the extent that 1H MRSI and MRI together with genetic and clinical measures identify changes consistent with early AD in non demented subjects (n=100) with a Clinical Dementia Rating of 0.5, compared to genetic and clinical measures alone. It is expected that this project will lead to the development of improved antemortem diagnostic technique (which could be used by many MR scanners) for: assessment of, screening of subjects at risk for, and monitoring progression of dementia.
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