Proton magnetic resonance spectroscopy in frontotemporal lobar degeneration-related syndromes

Objective To measure cortical metabolite deficits in vivo in syndromes associated with frontotemporal lobar degeneration, in relation to cognitive and behavioral change. Methods Sixty patients were recruited with a clinical syndrome associated with frontotemporal lobar degeneration (behavioral variant frontotemporal dementia n=11, progressive supranuclear palsy n=26, corticobasal syndrome n=11, primary progressive aphasias n=12), and 38 age- and sex-matched healthy controls. We measured nine metabolites in the right inferior frontal gyrus, superior temporal gyrus and right primary visual cortex using 3T semi-laser magnetic resonance spectroscopy. Metabolite concentrations were corrected for age, sex, and partial volume. We related corrected metabolite concentrations to cognitive and behavioral measures using canonical correlation analysis. Results Metabolite concentrations varied significantly by brain region and diagnosis (region x metabolite x diagnosis interaction F(64)=1.73, p<0.001, corrected for age, sex, and atrophy within the voxel). N-acetyl aspartate and glutamate concentrations were reduced in the right prefrontal cortex in behavioral variant frontotemporal dementia and progressive supranuclear palsy, even after partial volume correction. The reduction of these metabolites was associated with executive dysfunction and behavioral impairment (canonical correlation analysis R=0.95, p<0.001). Conclusion Magnetic resonance spectroscopy confirms behaviourally relevant metabolite deficits including glutamate, in syndromes associated with frontotemporal lobar degeneration. Magnetic resonance spectroscopy may be a useful index of neurodegeneration, and highlight candidates for pharmacological treatment.