Background: Traumatic brain injury (TBI) has been implicated as a potential risk factor for Parkinson's disease (PD). However, studies in underrepresented populations, including Mexicans, remain limited. Objectives: This study examines the association between TBI and PD and whether this association changes depending on sex. Methods: This multicenter, cross-sectional study involved 443 PD patients and 525 controls recruited from two national research cohorts. PD diagnoses adhered to UK Brain Bank criteria, and TBI history was retrospectively assessed through structured interviews. TBI was defined as a head injury with loss of consciousness or amnesia. Statistical analyses included binomial logistic regressions, adjusted odds ratios (aOR), and multivariate logistic regression model adjusted for age and sex. Results: No differences in TBI reported by PD patients (19.86%) compared with controls (16.76%), restricted to pre-diagnosis events (p = 0.87). However, reporting more than one TBI was significantly associated with PD, increasing the association of developing PD (aOR = 2.36; 95% CI: 1.02¿5.77; p = 0.05). Furthermore, men with a history of TBI had a significantly higher association of developing PD compared with women (aOR = 3.42; 95% CI: 1.97¿6.22; p < 0.001). Conclusions: These results indicate a possible link between TBI history and PD, particularly in males and those with repeated TBIs. Although TBI emerges as a potential non-genetic risk factor, further longitudinal research is necessary to determine causality and elucidate the underlying biological mechanisms.
