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H06 Cross sectional and longitudinal 3T magnetic resonance spectroscopy in a TRACK-HD cohort of individuals with premanifest and early Huntington's disease

Background A potential biomarker role for magnetic resonance spectroscopy (MRS) in Huntington's disease (HD) is unclear due to conflicting reports in the literature. Aim To investigate MRS as an HD biomarker through cross sectional and longitudinal examinations in a TRACK-HD study cohort. Methods Cross sectional MRS of the left putamen (at 3T field strength) was performed in the University of British Columbia TRACK-HD study cohort. 84 individuals (30 controls (C), 25 pre-HD (P), 29 early HD (E)) were scanned at baseline. 78 individuals (29 (C), 26 (P) and 23 (E)) underwent repeat MRS examination at 1 year. Metabolites of interest were total N-acetyl aspartate (tNAA) and myo-inositol (MI); markers of neuronal health and gliosis. Results Baseline tNAA concentrations in early HD were lower than in controls (mean (SD) 8.6 (0.7) mM (C) vs 7.3 (1.2) mM (E); p<0.001). MI was higher in early HD compared with controls (6.0 (2.6) mM (E) vs 4.3 (1.4) mM (C); p<0.005). After 1 year, MI concentrations remained 40% higher in early HD (6.0 (2.7) mM (E) vs 4.2 (1.1) mM (C); p<0.01). tNAA was still lower in early HD (p<0.001) but also in pre-HD (p<0.05) than controls (7.4 (0.9) mM (E) vs 8.2 (0.8) mM (P) vs 8.7 (0.6) mM (C)). Neither tNAA nor MI exhibited longitudinal change in any group. A novel observation was that of 30% increases in spectral linewidth in early HD at both time points (p<0.01). Conclusions Our data support patterns of higher MI levels and lower tNAA in early HD. The pattern of lower tNAA may begin in premanifest HD. The lack of longitudinal metabolite change is not unusual over such a short duration of follow-up. We also identified for the first time, consistent increases in MRS spectral linewidth in early HD.