N-acetyl-aspartate and Myo-inositol as Markers of White Matter Microstructural Organization in Mild Cognitive Impairment: Evidence from a DTI-(1)H-MRS Pilot Study

We implemented a multimodal approach to examine associations between structural and neurochemical changes that could signify neurodegenerative processes related to mild cognitive impairment (MCI). Fifty-nine older adults (60–85 years; 22 MCI) underwent whole-brain structural 3T MRI (T1W, T2W, DTI) and proton magnetic resonance spectroscopy ((1)H-MRS). The regions of interest (ROIs) for (1)H-MRS measurements were the dorsal posterior cingulate cortex, left hippocampal cortex, left medial temporal cortex, left primary sensorimotor cortex, and right dorsolateral prefrontal cortex. The findings revealed that subjects in the MCI group showed moderate to strong positive associations between the total N-acetylaspartate to total creatine and the total N-acetylaspartate to myo-inositol ratios in the hippocampus and dorsal posterior cingulate cortex and fractional anisotropy (FA) of WM tracts crossing these regions—specifically, the left temporal tapetum, right corona radiata, and right posterior cingulate gyri. In addition, negative associations between the myo-inositol to total creatine ratio and FA of the left temporal tapetum and right posterior cingulate gyri were observed. These observations suggest that the biochemical integrity of the hippocampus and cingulate cortex is associated with a microstructural organization of ipsilateral WM tracts originating in the hippocampus. Specifically, elevated myo-inositol might be an underlying mechanism for decreased connectivity between the hippocampus and the prefrontal/cingulate cortex in MCI.