Figure 1. Study design and eligible study participants. (A) Epigenetic aging data were measured among a randomly selected subset of CARDIA participants at year (Y) Y15 and Y20. Brain aging data were measured at a subset of participants at Y25 and Y30. Cognitive function tests were performed at Y25 and Y30 across almost all CARDIA participants. The DNA methylation was measured at earlier visits before brain MRI because molecular changes could occur years before the brain structural changes. Besides, as a blood-based marker, epigenetic age can be cost-effectively measured at an earlier age. (B) Among the 1,042 Y15 and 957 Y20 participants who had methylation data, 881 had methylation data at both visits. Among the 719 Y25 and 662 Y30 participants who had brain MRI data, 488 had MRI data at both visits. About 95% of the CARDIA participants at Y25 and Y30 had cognitive function data. To maximize statistical power, those who had available DNA methylation and cognitive function data were eligible for epigenetic age analysis (a union set of 1,115 participants involved); those who had available brain MRI and cognitive function data were eligible for brain age analysis (a union set of 887 participants involved). There were 326 overlapping participants who had both DNA methylation and brain MRI data.