TNF and major depressive disorder: Furthermore, contrasting individuals with the lowest values (i.e., 1st quartile) vs. those with the highest values in these measures (i.e., 4th quartile) resulted in BrainAGE differences of 3.4 years for smoking duration (p < 0.01), 4.1 years for alcohol intake (p < 0.01), 5.4 years for TNFα (p < 0.01), 5.6 years for verbal fluency (p < 0.001), and 5.4 years for depression (p < 0.01; Figure 9A), with all results being independent of diabetes duration, gender, and age (41).