Bladder cancer therapy with BCG vaccine may reduce risk for Alzheimer’s, related dementias
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Key takeaways:
- Researchers observed the potential protective effect when accounting for death as a competing event.
- Patients aged older than 70 years at the time of vaccine treatment had lower risk than younger patients.
The BCG vaccine appeared associated with a significantly lower rate of and risk for Alzheimer’s disease and related dementias among patients with nonmuscle-invasive bladder cancer, according to data published in JAMA Network Open.
Researchers observed the potential protective effect when accounting for death as a competing event. They noted that risk differences varied over time.
“The team, consisting of several uro-oncologists, as well as Alzheimer’s disease researchers, [also] was surprised and excited to see the striking association of BCG treatment with lower mortality,” Marc S. Weinberg, MD, PhD, principal investigator and physician in the Alzheimer’s clinical and translational research unit at Massachusetts General Hospital, told Healio. “This was not our primary goal of the study but may suggest that BCG should be studied for potential benefits to mortality outside of the context of neurologic disease.”
Background and methodology
The BCG vaccine is used worldwide to prevent tuberculosis, but the intravesical BCG vaccine is currently the recommended treatment for nonmuscle-invasive bladder cancer.
The vaccine has been hypothesized to reduce risk for Alzheimer’s disease and related dementias, but prior studies investigating such associations have had several limitations.
Weinberg and colleagues conducted a cohort study of 6,467 patients aged older than 50 years initially diagnosed with nonmuscle-invasive bladder cancer between 1987 and 2021 and treated within the Massachusetts General Brigham health care system. Among them, 3,388 (mean age, 69.89 years; 76.9% men) underwent BCG vaccine treatment. The other 3,079 participants (mean age, 70.73 years; 70.7% men) served as controls.
Researchers evaluated 15-year follow-up data of participants whose disease did not clinically progress to muscle-invasive cancer within 8 weeks and who did not have a diagnosis of Alzheimer’s disease and related dementias within a year after their cancer diagnosis.
Time to Alzheimer’s disease and related dementias onset identified through diagnosis codes and medications served as the main outcome.
Results
Treatment with BCG vaccine appeared associated with a lower rate of Alzheimer’s disease and related dementias (HR = 0.8; 95% CI, 0.69-0.99), with an even lower rate among patients aged 70 years or older at the time of treatment (HR = 0.74; 95% CI, 0.6-0.91).
Results of a competing risk analysis showed an association of BCG vaccine treatment with a lower risk for Alzheimer’s disease and related dementias (5-year risk difference, 0.011; 95% CI, 0.019 to 0.003) and a decreased risk for death among patients who did not have an earlier diagnosis (5-year risk difference, 0.056; 95% CI, 0.075 to 0.037).
Next steps
Additional trials will assist in further analyzing the relationships identified in this study, researchers wrote.
“Although our full study took several years to complete, preliminary findings and the generosity of the Alzheimer’s Association and its supporters allowed us to initiate a series of small clinical trials of BCG vaccination in 2020,” Weinberg told Healio. “The results of that study are intended to provide proof of principle that the BCG vaccine is safe and can impact the older adult’s immune system as hypothesized.
“We are studying BCG effects on cognition, and on blood and cerebrospinal fluid markers of immune function and Alzheimer’s disease,” he added. “Right now we are analyzing that data, but already are thinking about the best design for a larger study.”
For more information:
Marc S. Weinberg, MD, PhD, can be reached at Department of Psychiatry, Massachusetts General Hospital, 149 13th St., 10-136, Charlestown, MA 02129; email: marc.weinberg@mgh.harvard.edu.
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