Heterogeneous treatment effects of BCG vaccine on Alzheimer's disease risk.

Background: This project has investigated the role of the Bacillus Calmette-Guérin (BCG) vaccine as a potential treatment against Alzheimer's disease (AD) and related dementias (ADRD).

Objective: To further establish that BCG treatment results in lower risk of ADRD through novel machine learning methods and to analyze the heterogeneity of treatment effects.

Methods: This retrospective cohort study was conducted from May 28, 1987 to May 6, 2021, in patients who were 50 years or older and were diagnosed with non-muscle-invasive bladder cancer (NMIBC). Follow-up duration was 15-years. Machine learning algorithms using survival analysis and the random forest algorithm were the primary methods of data analysis.

Results: The research has found that on average, NMIBC patients who received BCG treatment had a 6.9% (95% CI: 0.43%, 13.4%) lower risk of developing ADRD compared to those who did not. Heterogeneous treatment effects were also detected for those with a history of mental health disorders and also for those with a history of respiratory diseases. Those with mental health disorders were at a 14.7% (95% CI: 0.6%, 28.9%) reduced risk of ADRD if they received BCG treatment compared to no BCG treatment. Additionally, those taking BCG with respiratory diseases increased risk of ADRD by 13.6% (95% CI: 1.1%, 26.1%) compared to those with no BCG treatment.

Conclusions: BCG is associated with a lower risk of ADRD through novel analysis methods and has detected heterogeneity of treatment effects. This presents BCG as a potential low-cost method, with few side-effects, to prevent ADRD.