Neurochemical changes in the progression of Huntington's disease: A meta-analysis of in vivo¹H-MRS studies

Proton magnetic resonance spectroscopy (¹H-MRS) allows measuring specific brain metabolic alterations in Huntington's disease (HD), and these metabolite profiles may serve as non-invasive biomarkers associated with disease progression. Despite this potential, previous findings are inconsistent. Accordingly, we performed a meta-analysis on available in vivo¹H-MRS studies in premanifest (Pre-HD) and symptomatic HD stages (Symp-HD), and quantified neurometabolic changes relative to controls in 9 Pre-HD studies (227 controls and 188 mutation carriers) and 14 Symp-HD studies (326 controls and 306 patients). Our results indicated decreased N-acetylaspartate and creatine in the basal ganglia in both Pre-HD and Symp-HD. The overall level of myo-inositol was decreased in Pre-HD while increased in Symp-HD. Besides, Symp-HD patients showed more severe metabolism disruption than Pre-HD patients. Taken together, ¹H-MRS is important for elucidating progressive metabolite changes from Pre-HD to clinical conversion; N-acetylaspartate and creatine in the basal ganglia are already sensitive at the preclinical stage and are promising biomarkers for tracking disease progression; overall myo-inositol is a possible characteristic metabolite for distinguishing HD stages.