Due to increased longevity, the number of people at risk for neurodegenerative brain disease is rising. Debilitating brain diseases are generally associated with neuronal loss. However, it remains controversial if neurons are also lost due to normal aging alone. Since there is no diagnostic technique to measure neuronal density in vivo, early differentiation between normal brain aging and a neurodegenerative disease is not possible To develop a diagnostic tool, we propose using a non-invasive technique of in vivo 1H magnetic resonance spectroscopic imaging, MRSI, which can measure brain concentrations of neuronal marker, N-acetyl aspartate (NAA) and total choline (Cho), which is more abundant in glial cells than in neurons. Initially, we propose to establish in vivo differences in brain concentrations of NAA and Cho between healthy young and aged brain, using high resolution, multi-slice MRSI. The hypotheses to be tested, are: 1. In the aged brain, the NAA concentration in selective brain regions will be lower and choline concentration will be higher than in the young brain. Lower NAA concentration will be consistent with lower neuronal density in those regions and higher choline concentration will be consistent with higher density of glial cells. 2. The NAA concentrations in specific brain regions will correlate with scores of neuropsychological tests that are associated with activation of these brain regions.
The specific aims are: 1.a) To measure absolute concentrations of NAA and total choline in multiple gray and white matter brain regions in four supratentorial brain slices, with the resolution of 0.8 ml. b) To identify brain regions that show metabolic differences between young and aged brain. 2. To perform a correlation analysis between specific neuropsychological test scores and cortical NAA concentrations. The study will be performed in two groups of subjects: healthy young (20-40 years old) and healthy old adults (65 years and older). The long-term goal of our research is development and validation of 1H MRSI (by longitudinal studies and comparison with methods of quantitative neuropathology) for monitoring of patients who are at risk for developing neurodegenerative disease and for detection of neurodegenerative diseases at an early stage, at a time, when treatment may be successful.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Small Research Grants (R03)
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Special Emphasis Panel (ZAG1-PCR-5 (M9))
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Johns Hopkins University
Schools of Medicine
United States
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