Sex-related differences in amyotrophic lateral sclerosis: A 2-[18F]FDG-PET study

Purpose: We investigated sex-related brain metabolic differences in Amyotrophic Lateral Sclerosis (ALS) and healthy controls (HC). Methods: We collected two equal-sized groups of male (m-ALS) and female ALS (f-ALS) patients (n = 130 each), who underwent 2-[F-18]FDG-PET at diagnosis, matched for site of onset, cognitive status and King's stage. We included 168 age-matched healthy controls, half female (f-HC) and half male (m-HC). We compared brain metabolism of males and females separately for ALS and HC, including age as covariate. A differential network analysis was performed to evaluate brain connectivity. Results: M-ALS showed relative hypometabolism of bilateral medial frontal, parietal and occipital cortices, and left temporal cortex, compared to f-ALS. In node-wise comparison, f-ALS showed significantly higher connectivity in right middle cingulate cortex and left superior and medial frontal gyrus. In HC we did not find any sex-related differences. Conclusion: Sex resulted a major determinant of brain metabolism and connectivity in ALS patients.