Head Impact Exposure, Gray Matter Volume, and Moderating Effects of Estimated Intelligence Quotient and Educational Attainment in Former Athletes at Midlife.

Repetitive head impact (RHI) exposure has been associated with differences in brain structure among younger active athletes, most often within the hippocampus. Studies of former athletes at early-midlife are limited. We investigated the association between RHI exposure and gray matter (GM) structure, as well as moderating factors, among former athletes in early-midlife. Former collegiate football players (n = 55; age = 37.9 + 1.5 years) completed magnetic resonance imaging to quantify GM morphometry and extensive structured interviews of RHI history (Head Impact Exposure Estimate). Linear regression models tested the association between RHI exposure and GM structures of interest. Interactions were tested for moderators: two estimates of intelligence quotient (IQ) (single word reading and picture vocabulary) and education history. Greater RHI exposure was associated with smaller hippocampal volume, β = -0.36, p = 0.004. Conversely, RHI exposure was not significantly associated with other GM outcomes ps > 0.05. Education history significantly moderated the association between RHI exposure and hippocampal volume, β = 0.31, p = 0.047. Among those with a bachelor's degree, greater RHI exposure was significantly associated with smaller hippocampal volumes, β = -0.58, p < 0.001. For those with graduate/professional degrees, the association between RHI and hippocampal volume was not significant, β = -0.33, p = 0.134. Consistent with studies involving younger, active athletes, smaller hippocampal volumes were selectively associated with greater RHI exposure among former collegiate football players at midlife. This relationship was moderated by higher levels of education. Future longitudinal studies are needed to investigate the course of possible changes that can occur between early-midlife and older ages, as well as the continued protective effect of education and other potential influential factors.