Reply to Biskup et al. and Tu et al.: Sex differences in metabolic brain aging

We greatly appreciate the interest and thoughtful insights into our study by both Biskup et al. (1) and Tu et al. (2). Their comments prompted us to further analyze the data published in our paper (3), as discussed below. Biskup et al. (1) first wonder whether our results might be due to the multiparametric nature of the dataset or, alternatively, could be related to a global difference in rationing between aerobic glycolysis (AG) and oxidative metabolism. We investigate this further by looking at each metabolic parameter independently. First, generalized linear modeling reveals that sex-based differences in regional gray matter AG (adjusted for chronological age) correlate well with how much a region’s AG varies with age (i.e., regions with higher AG in females are also those that lose the most AG with age, Pearson’s r = 0.72), suggesting that more typical statistical analysis for AG alone reflects the results from our multiparametric machine learning model. Next, we investigated whether sex-based differences in metabolic brain age persist when calculated independently for AG, total glucose use (CMRGlc), oxygen … [↵][1]1To whom correspondence should be addressed. Email: goyalm{at}wustl.edu. [1]: #xref-corresp-1-1