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IC‐P‐054: MAGNETIC RESONANCE SPECTROSCOPY INVESTIGATIONS OF EFFECTS OF GLUCOSE IN NORMAL AGING BRAIN
Author(s) -
Harris Janna,
Brooks William Miles,
Yeh HungWen,
Choi InYoung,
Swerdlow Russell H.
Publication year - 2014
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2014.05.059
Subject(s) - neurochemical , glutamine , hippocampus , endocrinology , glutamate receptor , medicine , human brain , analysis of variance , chemistry , neuroscience , psychology , biochemistry , amino acid , receptor
Background:As the human brain ages, cellular mechanisms such as bioenergetics, inflammation, oxidative stress, and membrane turnover are altered, possibly contributing to the cognitive decline seen in otherwise healthy elderly. Accordingly, there is a need for non-invasive methods to provide quantitative assessment of the state of each of these mechanisms. Localized, non-invasive magnetic resonance spectroscopy (MRS) of the brain can quantify a neurochemical profile of at least 20 neurochemicals that have been associated with these cellular mechanisms. Methods: We used noninvasive high-field 9.4 Tesla short-echo STEAM MRS to quantify neurochemicals in the hippocampus and sensorimotor cortex of young adult (23mo, n1⁄430) and aged (20-22mo, n1⁄420) male Fischer 344 rats. Animals were housed in pairs on a 12 hour light-dark cycle with free access to standard rat chow and water. Animals were anesthetized with isoflurane for scanning in accordance with institutional guidelines. We used LCModel to calculate absolute concentrations of 20 neurochemicals using a weighted averages method to account for variable signal quality. We applied a mixedeffects ANOVA model (age, location, age*location) and implemented the Holm’s sequential Bonferroni procedure to control the family-wise type I error rate at the 0.05 level. Results: We found significant differences in the neurochemical profile of the aged brain when compared with younger adults, including higher glucose, myoinositol, and glutamine, and lower aspartate, ascorbate, and glutamate (all p<0.05). Across all spectra, we found that glucose was negatively correlated with lactate (r 2 1⁄40.32), possibly reflecting individual glycolytic state. We also found that in each brain location glucose was correlated with myo-inositol (r 2 1⁄40.37 in hippocampus and r 21⁄40.38 in cortex). Since myo-inositol is a marker of astrocytes, we speculate that this may reflect the pro-inflammatory effects of higher brain glucose. Conclusions: Although the specific mechanisms underlying altered spectroscopic biomarkers remain to be verified, MRSmight be a useful non-invasive approach to studying inflammation in normal aging and in disease. Although the current study was completed on a high-field pre-clinical scanner, novel techniques to quantify these biomarkers in humans are under development. Accordingly, MRS is a promising translational approach for assessing the state of the aging brain and for studying novel treatments.