Medial Parietal Cortex GABA Measurements in Alzheimer’s Disease Are Inversely Associated with Functional Response (P6.316)

Objective We investigated in vivo GABA levels within the medial parietal lobe, measured using cerebral proton magnetic resonance spectroscopy (MRS), and their relation to the functional magnetic resonance (fMRI) response in this region in patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI). Background In vivo MRS measurements of GABA have been shown to correlate with measured fMRI signal in healthy adults. The association between this MR-measurable inhibitory neurotransmitter and fMRI activity has yet to be demonstrated in the AD population. Given the potential contribution of GABA to the disease process in AD, greater levels of GABA in AD would imply pathological significance. Design/Methods 16 subjects performed an auditory verbal memory task and a reading task while fMRI sequences were acquired. Following this, cerebral proton MRS data were acquired with GABA editing from a voxel placed in the medial parietal lobe. GABA levels were corrected for cortical volume in the region of interest. The blood oxygen level dependent (BOLD) response was correlated with the corrected GABA level. Results There was a significant negative correlation between GABA levels and cognitive scores, indicating greater GABA in patients with AD, compared to controls or MCI. Measured GABA correlated negatively to fMRI activity in the medial parietal cortex during both auditory memory and reading. Correcting GABA measurements for cortical volume, resulted in a strengthening of these correlations. Conclusions/Relevance These results establish a link between inhibitory neurotransmitter levels, measured by in vivo cerebral MRS and reduced functional activity using fMRI in this patient population and points towards imbalances in neurotransmitter tone as the AD pathological process progresses. These results have potential therapeutic implications. These techniques afford objective mechanisms to observe treatment response in future clinical trials. Disclosure: Dr. Dhanjal has nothing to disclose. Dr. McPhail has nothing to disclose. Dr. Wylezinska has nothing to disclose. Dr. Wise has received personal compensation in an editorial capacity for the journal Neuropsychologia.,