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.