Repeated measures analysis of variance were conducted to assess changes in circulating factors over time. Significant changes over time are indicated by P values. Complete data for all parameters on both time points were available for 110 participants, except for interleukin-1β (IL-1β), for which data from 111 participants were available. For illustrative purposes 3 extreme high IL-1β values (7.59 pg/mL, 12.75 pg/mL, and 3.94 pg/mL) at baseline are not shown. At the 2 year time point, 2 extreme high IL-1β values (5.12 and 3.26 pg/mL) was not included for illustrative purposes. Individual values for every plasma marker are presented in eTable 4 in Supplement 1. BDNF indicates brain derived neurotrophic factor; NFL = neurofilament light chain; PAI-1 plasminogen activator inhibitor-1. Dots indicate individual data points; bars, medians; bars, IQRs; and whiskers, ranges.