Long-Term Impact of Historical BCG Vaccination Policies on Parkinson's Disease Risk: A Hypothesis-Generating...

Objectives: Adults exposed to the Bacillus Calmette-Guérin (BCG) vaccine demonstrate a reduced incidence of Parkinson's disease (PD). This retrospective study evaluated whether early-life BCG vaccination predicts a long-term reduction in PD incidence during aging. Methods: Published age-adjusted incidence rates (AAIRs) of PD (2002-2021) were structured into single-age birth cohorts. Missing values were calculated via interpolation and shuffling simulations. Cohorts were categorized into three historical BCG policy periods: unvaccinated controls (born 1945-1949), vaccinated at age 12 (born 1950-1954), and vaccinated as newborns (born 1955-1959). AAIRs were compared at identical cross-sectional ages (57 and 62 years), applying an environmental drift penalty to control for temporal improvements. Results: In men, the age 12 policy showed a 21.8% AAIR reduction at age 57, which attenuated to 4.4% by age 62; the newborn policy showed a sustained reduction (25.8% at age 57; 20.4% at age 62). In women, the age 12 policy yielded a 67.5% reduction at age 57 (33.1% at age 62), while the newborn policy showed a 56.8% reduction at age 57 (44.0% at age 62). Conclusions: Early-life BCG vaccination is associated with reduced later-life PD incidence, displaying a profound sex-dependent effect favoring females. Newborn vaccination provides long-term resistance as well.