AN MRI-DERIVED DISEASE MARKER IS ASSOCIATED WITH CONVERSION TO MCI IN MIDDLE-AGED ADULTS AT RISK FOR AD

task-based fMRI responses and MRS measures in patients with Alzheimer’s disease (AD), amnestic mild cognitive impairment (MCI) and healthy matched controls.Methods:Data were collected from 29 participants: 9 with mild-to-moderate AD, 7 with MCI and 13 ageand education-matched controls. Two task-based fMRI scans were performed: a silent reading task and an auditory verbal memory task. Anatomical data were collected to correct for differences in regional cortical volume, largely as a consequence of atrophy. MRS data were then acquired from a voxel placed in the medial parietal region, including standard proton MRS and GABA-edited MRS measures. Whole-brain and regional analyses of fMRI data were performed. The blood oxygen level dependent responses (BOLD) from each fMRI study were correlated with GABA-edited MRS data. Results: There were significantly lower levels of N-acetylaspartate in AD compared to controls. Significantly higher levels of myoinositol, choline and GABA were seen in AD, compared to both controls and patients with MCI. FMRI responses were reduced in the medial parietal region during both tasks in patients with AD, compared to controls. GABA levels correlated negatively with fMRI data from the medial parietal region during both the reading task and the verbal memory task. Conclusions: Our results suggest changes in inhibitory neurotransmitter tone with progression of the pathological changes associated with AD. This change is correlated with the fMRI responses observed in this patient population. These findings provide further insight into fMRI measurements in this patient population. In addition, the results suggest potential therapeutic implications.