Brain MR Spectroscopy Changes Precede Frontotemporal Lobar Degeneration Phenoconversion in Mapt Mutation Carriers.

BACKGROUND AND PURPOSE The objective of this study was to longitudinally investigate the trajectory of change in H-1 MRS measurements in asymptomatic MAPT mutation carriers who became symptomatic during follow-up, and to determine the time at which the neurochemical alterations accelerated during disease progression. METHODS We identified eight MAPT mutations carriers who transitioned from asymptomatic to symptomatic disease during follow-up. All participants were longitudinally followed with an average of 7.75 years (range 4-11 years) and underwent two or more single voxel H-1 MRS examinations from the posterior cingulate voxel, with a total of 60 examinations. The rate of longitudinal change for each metabolite was estimated using linear mixed models. A flex point model was used to estimate the flex time point of the change in slope. RESULTS The decrease in the NAA/mI ratio accelerated 2.09 years prior to symptom onset, and continued to decline. A similar trajectory was observed in the presumed glial marker mI/Cr ratio accelerating 1.86 years prior to symptom onset. CONCLUSIONS Our findings support the potential use of longitudinal H-1 MRS for monitoring the neurodegenerative progression in MAPT mutation carriers starting from the asymptomatic stage.