Ic‐p‐114: Relating Hippocampal Glutamate to Structural Changes and Cognitive Performance in Alzheimer's Disease: A 7t Mri Study

Diagnosis and prognosis in Alzheimer's disease (AD) remains a significant challenge. Development of MRI biomarkers could help meet this need. We previously observed decreased hippocampal glutamate (Glu) levels in AD using proton magnetic resonance spectroscopy (1H-MRS) at 4T, and proposed this as an AD biomarker. In this study, we extend that work by measuring hippocampal and posterior cingulate Glu levels using ultra-high field (7T) MRI and relating them to measures of neurodegeneration and cognitive performance. Cognitively normal elderly controls (NEC, n=13, 74±7.3 years), individuals with mild cognitive impairment (MCI, n=6, 75±10 years), and individuals with prodromal AD (AD, n=7, 79±7.9 years) were studied. Single-voxel 1H-MRS data were acquired from the left hippocampus (23x12x12 mm3) and posterior cingulate cortex (PCC, 16x20x18 mm3). Maps of fractional anisotropy (FA) were obtained using diffusion weighted imaging. Tractography was performed to find the main hippocampal-PCC white-matter fibre tract connecting the two spectroscopy voxels (Figure 1). Cognitive performance was assessed using the National Alzheimer's Coordinating Center Neuropsychological Battery, Version 3.0. Relationships between Glu levels, tract FA, and cognitive measurements were assessed. Lower hippocampal Glu levels were observed in MCI compared to NEC (p < 0.05) and as a trend in AD compared to NEC (p = 0.07, Figure 2). In the hippocampal-PCC tract, tract FA values were lower in AD compared to NEC and varied along the tract (Figure 3). Hippocampal Glu was positively correlated with average tract FA (r = 0.59, p < 0.05) and cognitive measurements including Figure Copy performance (r = 0.48, p < 0.05). Figure Copy performance was also positively associated with average tract FA (r = 0.48, p < 0.05). PCC Glu levels were not significantly different between groups or related to tract FA or cognitive measurements.