LAUSR

BACKGROUND In recent years, magnetic resonance spectroscopy (MRS) has benefited from increased MRI field strengths, new acquisition protocols, and new processing techniques. This review aims to determine how this has altered our understanding of MRS neurometabolic markers in neurodegenerative dementias. METHODS Our systematic review of human in vivo MRS literature since 2002 pertains to Alzheimer's disease (AD), dementia with Lewy bodies (DLB), Parkinson's disease dementia, frontotemporal dementia (FTD), prodromal and 'at risk' states. Studies using field strengths ≥3T were included. RESULTS Of 85 studies, AD and/or mild cognitive impairment (MCI) were the most common conditions of interest (58 papers, 68%). Only 14(16%) studies included other dementia syndromes and 13(15%) investigated 'at risk' cohorts. Earlier findings of lower N-acetylaspartate and higher myo-Inositol were confirmed. Additionally, lower choline and creatine in AD and MCI were reported, though inconsistently. Previously challenging-to-measure metabolites: glutathione, glutamate, and gamma-aminobutyric acid were reportedly lower in AD, FTD and DLB compared to controls. DISCUSSION Increasing field strength alongside targeted acquisition protocols has revealed additional metabolite changes. Most studies were small and regional metabolite differences between dementia types may not have been captured due to the predominant placement of voxels in the posterior cingulate cortex. The standard of data collection, quality control and analysis is improving due to greater consensus regarding acquisition and processing techniques. Ongoing harmonisation of techniques, creation of larger and longitudinal cohorts, and placement of MRS voxels in more diverse regions will strengthen future research.