Association of BCG Vaccine Treatment With Death and Dementia in Patients With Non–Muscle-Invasive Bladder Cancer

Abstract

ImportanceThe BCG vaccine—used worldwide to prevent tuberculosis—confers multiple nonspecific beneficial effects, and intravesical BCG vaccine is currently the recommended treatment for non–muscle-invasive bladder cancer (NMIBC). Moreover, BCG vaccine has been hypothesized to reduce the risk of Alzheimer disease and related dementias (ADRD), but previous studies have been limited by sample size, study design, or analyses.ObjectiveTo evaluate whether intravesical BCG vaccine exposure is associated with a decreased incidence of ADRD in a cohort of patients with NMIBC while accounting for death as a competing event.Design, Setting, and ParticipantsThis cohort study was performed in patients aged 50 years or older initially diagnosed with NMIBC between May 28, 1987, and May 6, 2021, treated within the Mass General Brigham health care system. The study included a 15-year follow-up of individuals (BCG vaccine treated or controls) whose condition did not clinically progress to muscle-invasive cancer within 8 weeks and did not have an ADRD diagnosis within the first year after the NMIBC diagnosis. Data analysis was conducted from April 18, 2021, to March 28, 2023.Main Outcomes and MeasuresThe main outcome was time to ADRD onset identified using diagnosis codes and medications. Cause-specific hazard ratios (HRs) were estimated using Cox proportional hazards regression after adjusting for confounders (age, sex, and Charlson Comorbidity Index) using inverse probability scores weighting.ResultsIn this cohort study including 6467 individuals initially diagnosed with NMIBC between 1987 and 2021, 3388 patients underwent BCG vaccine treatment (mean [SD] age, 69.89 [9.28] years; 2605 [76.9%] men) and 3079 served as controls (mean [SD] age, 70.73 [10.00] years; 2176 [70.7%] men). Treatment with BCG vaccine was associated with a lower rate of ADRD (HR, 0.80; 95% CI, 0.69-0.99), with an even lower rate of ADRD in patients aged 70 years or older at the time of BCG vaccine treatment (HR, 0.74; 95% CI, 0.60-0.91). In competing risks analysis, BCG vaccine was associated with a lower risk of ADRD (5-year risk difference, −0.011; 95% CI, −0.019 to −0.003) and a decreased risk of death in patients without an earlier diagnosis of ADRD (5-year risk difference, −0.056; 95% CI, −0.075 to −0.037).Conclusions and RelevanceIn this study, BCG vaccine was associated with a significantly lower rate and risk of ADRD in a cohort of patients with bladder cancer when accounting for death as a competing event. However, the risk differences varied with time.

The role of Bacillus Calmette-Guérin administration on the risk of dementia in bladder cancer patients: a systematic review and meta-analysis

“…Due to the long-term non-specific immune effects of BCG exposure, a hypothesis that BCG could decrease the prevalence of AD in the elderly population was proposed (Gofrit et al, 2019a), which was investigated subsequently, and several claims were made previously. First, previous studies supported that BCG treatment is associated with a reduced risk of developing AD or other dementias (Gofrit et al, 2019b;Kim et al, 2021;Klinger et al, 2021;Makrakis et al, 2022;Weinberg et al, 2023). Second, old age was usually known as a risk factor for developing AD (Makrakis et al, 2022).…”

Periodontitis and the risk of all‐cause and cause‐specific mortality among US adults with diabetes: A population‐based cohort study

“…Details of the missing rates for covariates and the method of multiple imputation are shown in Table S1 and Appendix S1. Adjusted absolute risk differences for 5 and 10 years based on the cumulative incidence information were used to summarize the association between PD and all‐cause mortality (Elhence et al, 2023; Wang et al, 2023; Weinberg et al, 2023). Cumulative incidence at 5 and 10 years were calculated based on multivariable adjusted Cox proportional hazards model (Model 3).…”

Can immunization with BCG delay the onset of Alzheimer's disease?

“…1 It is estimated that the number of PwD living alone will reach 1.47 million by 2025 and 1.81 million by 2040. 2 However, to our knowledge, there are no previous studies on the incidence rate (IR) of missing PwD living alone. Thus, the purpose of this study was to clarify the IR of missing PwD living alone.…”

“…Thus far, five retrospective studies examined the effect of intravesical BCG on the odds ratio of dementia in patients with bladder cancer from different ethnologic backgrounds, both in community settings and in tertiary centers (Table 1). [2][3][4][5][6] These studies included 19 983 BCG treated and 27 222 untreated patients. All studies showed significant decrease in the odds ratio of dementia in patients treated with BCG.…”

“…3 Two studies also documented a dose-dependent relation between the number of the BCG instillations and the effect on dementia. 2,5 How can BCG given intravesicaly decrease the occurrence of AD? BCG induces different local and systemic responses.…”