1H-MRS neurometabolites and associations with neurite microstructures and cognitive functions in amnestic mild cognitive impairment

Alzheimer's disease (AD) pathogenesis is associated with alterations in neurometabolites and cortical microstructure. However, our understanding of alterations in neurochemicals in the prefrontal cortex and their rela-tionship with changes in cortical microstructure in AD remains unclear. Here, we studied the levels of neurometabolites in the left dorsolateral prefrontal cortex (DLPFC) in healthy older adults and patients with amnestic Mild Cognitive Impairments (aMCI) using single-voxel proton-magnetic resonance spectroscopy (H-1-MRS). N-acetyl aspartate (NAA), glutamate+glutamate (Glx), Myo-inositol (mI), and gamma-aminobutyric acid (GABA) brain metabolite levels were quantified relative to total creatine (tCr = Cr + PCr). aMCI had significantly decreased NAA/tCr, Glx/tCr, NAA/mI, and increased mI/tCr levels compared with healthy controls. Further, we leveraged advanced diffusion MRI to extract neurite properties in the left DLPFC and found a significant positive correlation between NAA/tCr, related to neuronal intracellular compartment, and neurite density (ICVF, intracellular volume fraction), and a negative correlation between mI/tCr and neurite orientation (ODI) only in healthy older adults. These data suggest a potential decoupling in the relationship between neurite microstructures and NAA and mI concentrations in DLPFC in the early stage of AD. Together, our results confirm altered DLPFC neurometabolites in prodromal phase of AD and provide unique evidence regarding the imbalance in the association between neurometabolites and neurite microstructure in early stage of AD.

Automated summary

This study investigated alterations in neurometabolites in the prefrontal cortex and their relationship with cortical microstructure in Alzheimer's disease (AD). The results showed significant changes in neurometabolite levels in patients with amnestic Mild Cognitive Impairments (aMCI) compared to healthy controls. Additionally, there were correlations between neuronal intracellular compartment and neurite density, as well as between neurite orientation and myo-inositol levels in healthy older adults only. These findings provide unique evidence regarding the imbalance in the association between neurometabolites and neurite microstructure in the early stage of AD.