Reduced Cerebral Blood Flow in the Early Chronic Phase of Recurrent Concussion Among Female Collegiate-Aged Athletes

The susceptibility of athletes to long-term adverse outcomes following recurrent concussion remains controversial. Acute concussion precipitates a transient reduction in cerebral blood flow (CBF) that typically returns to pre-injury levels. Recent work suggests that long-term CBF alterations may be sex-specific. We assessed whether concussion history was associated with chronic CBF alterations and whether sex moderated this relationship in otherwise healthy, active collegiate-aged athletes. Collegiate-aged athletes from the community (N = 204, 37.8% female, M_age = 21.0 ± 1.7) underwent magnetic resonance imaging with pseudo-continuous arterial spin labeling to quantify global and regional CBF and spatial coefficient of variation. Participants also completed measures of depression, anxiety, and cognition. Multiple linear regressions incorporating prior concussion-by-sex interaction terms adjusted for relevant covariates were fit to estimate the extent to which sex moderated the concussion history-CBF relationship. Exploratory analyses further assessed whether oral contraceptive use or pill formulation moderated this association in females. The number of prior concussions was negatively associated with global and regional gray-matter CBF in female but not male athletes, with the strongest associations localizing to frontotemporal regions. CBF metrics were not related to cognitive performance or affective symptom burden. Contraceptive use did not appear to substantially moderate the concussion history-CBF association in female athletes. Female-specific associations between concussion history and cerebral hypoperfusion in early adulthood suggest potential sex differences in pathways and trajectories of adverse long-term outcomes. Early chronic CBF alterations may represent one vulnerability to future risk in a sex-specific manner.