Extended Data Fig. 3: Annual changes in brain volumes associated with candidate proteins as a function of infection.

Line graphs display annual changes in temporal gray matter volumes associated with PRDX5 levels as a function of a influenza and b skin/subcutaneous infections in the Baltimore Longitudinal Study of Aging. To improve interpretation, the effects of PRDX5 are displayed based on lower/upper PRDX5 quartiles (continuous PRDX5 levels were used in analyses). Adjusted differences in annual changes of standardized brain volumes associated with history of a given infection were derived from linear mixed-effects models (n = 1,184) adjusted for intracranial volume, baseline age, sex, race, education, APOEε4, a comorbidity index (that is, obesity, hypertension, diabetes, cancer, ischemic heart disease, chronic heart failure, chronic kidney disease, and chronic obstructive pulmonary disease), and two-way interactions of covariates with time, as well as two-way and three-way interaction terms (infection*protein, infection*protein*time) to examine whether an infection diagnosis modified the association of protein level with longitudinal brain volume change. The displayed associations reflect statistically significant relationships. Statistical significance was defined at two-sided p < 0.05 without adjustment for multiple comparisons. The exact p-values are presented in the source data files, Supplementary Table 17.