Sex differences in the aging brain? A voxel-based morphometry analysis of the hippocampus and the amygdala

Objectives Volumetric reductions in the hippocampus and the amygdala are considered a hallmark for many psychiatric and neurodegenerative disorders. Because brain atrophy is often observed in disorders that have a higher prevalence in females than males, it has been proposed that sex differences in the aging brain represent a vulnerability factor for developing more severe psychiatric conditions. Methods Sexual dimorphism was assessed in the amygdala volume and hippocampal volume in a large sample (N = 554) of healthy individuals ranging from 20 to 79 years old, using structural brain data available from a public dataset. Results In both the hippocampus and the amygdala, a quadratic association was found between age and brain volume. Using uncorrected data for head size [total intracranial volume (TIV)], males clearly demonstrated larger amygdala and hippocampal volume across all ages, and an interaction between age and sex in the hippocampus supported the hypothesis of accelerated atrophy in the hippocampus in later life (60-79 years old). However, when volumetric data adjusted for TIV were used, sex differences were not observed in the hippocampus nor the amygdala. Conclusion These findings support the extensive series of studies suggesting that sex differences in brain volume are likely related to the confounding effect of head size. While continued effort is allocated to identify sex-related biomarkers, increasing evidence suggests that sexual dimorphism in the hippocampus or the amygdala does not appear to be the primary candidates for precision medicine to identify sex-related biomarkers that index potential vulnerabilities.