Summary: A new study indicates that the Bacillus Calmette-Guérin (BCG) vaccine—commonly used against tuberculosis and routinely administered as an intravesical therapy for non–muscle-invasive bladder cancer—may be linked to a lower risk of Alzheimer’s disease and related dementias (ADRD). Researchers also observed a reduction in overall mortality among patients who received BCG treatment.
Investigators tracked 6,467 patients for up to 15 years after diagnosis with non–muscle-invasive bladder cancer. Among those, 3,388 patients received intravesical BCG treatment while 3,079 matched controls did not. The study found a 20% lower risk of ADRD and a 25% lower risk of death in the BCG-treated group, with the protective association appearing strongest in patients aged 70 and older.
The research team plans to pursue clinical trials to evaluate whether BCG vaccination can directly prevent or delay Alzheimer’s disease in older adults.
Key Facts:
- The BCG vaccine was associated with a 20% reduced risk of Alzheimer’s disease and related dementias in this cohort.
- The study followed 6,467 adults diagnosed with non–muscle-invasive bladder cancer over as many as 15 years.
- BCG treatment was also associated with a 25% lower risk of death, and the protective effect against ADRD was more pronounced in patients aged 70 years or older.
Source: Mass General
Background: The BCG vaccine, widely used worldwide for tuberculosis prevention, has known nonspecific immune-modulating effects. Intravesical BCG is the recommended therapy for non–muscle-invasive bladder cancer (NMIBC). Prior studies have hinted at an association between BCG exposure and reduced dementia risk, but limitations in study size and design have left uncertainty about the strength and reproducibility of this link.
To address these gaps, researchers at Massachusetts General Hospital (MGH) and Brigham and Women’s Hospital (BWH) performed a larger, longer-term cohort study. The results were published in JAMA Network Open.
The cohort included patients aged 50 years or older who were diagnosed with NMIBC between 1987 and 2021 and treated within the Mass General Brigham health care system. Individuals were eligible if their cancer did not progress to muscle-invasive disease within eight weeks and if they had no diagnosis of ADRD within the first year after the NMIBC diagnosis. Follow-up extended up to 15 years, and researchers used diagnosis codes and medication records to identify incident ADRD.
During follow-up, 202 patients in the BCG group and 262 in the control group developed ADRD. These counts corresponded to incidence rates of 8.8 and 12.1 per 1,000 person-years, respectively. After adjustment for age, sex, and medical comorbidities using inverse probability score weighting, treatment with BCG was associated with a 20% lower hazard of ADRD (hazard ratio, 0.80). The effect was stronger among patients aged 70 years or older at the time of treatment (hazard ratio, 0.74).
Mortality analyses showed 751 deaths in the BCG group versus 973 deaths among controls during follow-up. Accounting for death as a competing event, BCG was associated with a 5-year absolute risk reduction in ADRD and a meaningful decrease in mortality risk among patients without an earlier ADRD diagnosis.
Lead author Marc Weinberg, MD, PhD, emphasized the public health implications: “A vaccine like BCG, if proven effective, could represent a cost-effective, population-level strategy to address a devastating condition such as Alzheimer’s disease.” The team is now shifting toward clinical trials focused on vaccinating older adults to test potential cognitive and disease-modifying effects directly.
If a causal relationship is confirmed, researchers will need to determine the mechanisms behind the association. The investigators note that BCG’s broad effects on the immune system may contribute to neuroprotective outcomes, but further mechanistic work is required.
Additional authors on the study include Sun Young Chung, Wesley H. Chou, Madhur Nayan, Mayuresh Deodhar, Daniel M. Frendl, Adam S. Feldman, Denise L. Faustman, Steven E. Arnold, Bella Vakulenko-Lagun, and others. The research received funding from the National Institutes of Health and the Alzheimer’s Association.
About this Alzheimer’s disease research news
Author: Brandon Chase
Source: Mass General
Contact: Brandon Chase – Mass General
Image: The image is credited to Neuroscience News
Original Research: Open access. “Association of BCG Vaccine Treatment With Death and Dementia in Patients With Non–Muscle-Invasive Bladder Cancer” by Marc Weinberg et al., JAMA Network Open.
Abstract
Association of BCG Vaccine Treatment With Death and Dementia in Patients With Non–Muscle-Invasive Bladder Cancer
Importance: Intravesical BCG is standard therapy for NMIBC and has been hypothesized to lower the risk of Alzheimer’s disease and related dementias due to its broad immunomodulatory effects. Prior studies were limited by design or sample size.
Objective: To determine whether exposure to intravesical BCG is associated with reduced incidence of ADRD in a cohort of patients with NMIBC, accounting for death as a competing event.
Design, Setting, and Participants: This cohort study included patients aged 50 years or older initially diagnosed with NMIBC between May 28, 1987, and May 6, 2021, within the Mass General Brigham system. The analysis excluded patients whose disease progressed to muscle-invasive cancer within eight weeks or who received an ADRD diagnosis within one year of NMIBC diagnosis. Data analysis occurred from April 18, 2021, to March 28, 2023.
Main Outcomes and Measures: Time to ADRD onset as identified by clinical diagnoses and medications. Cause-specific hazard ratios were estimated using Cox proportional hazards models adjusted for age, sex, and Charlson Comorbidity Index via inverse probability score weighting.
Results: Among 6,467 eligible patients, 3,388 received BCG (mean age 69.9 years; 76.9% men) and 3,079 served as controls (mean age 70.7 years; 70.7% men). BCG treatment was associated with a lower rate of ADRD (HR, 0.80; 95% CI, 0.69–0.99) and a stronger association in patients aged 70+ (HR, 0.74; 95% CI, 0.60–0.91). Competing risks analysis showed a 5-year risk difference for ADRD of −0.011 (95% CI, −0.019 to −0.003) and a decreased 5-year risk of death in patients without prior ADRD (risk difference, −0.056; 95% CI, −0.075 to −0.037).
Conclusions and Relevance: In this long-term cohort of patients with NMIBC, intravesical BCG treatment was associated with a significantly lower rate and risk of ADRD when accounting for competing mortality. These results support further investigation, including prospective clinical trials, to test causality and uncover underlying biological mechanisms.