Bladder instillations of bacillus Calmette-Guérin (BCG) in patients with nonmuscle-invasive bladder cancer (NMIBC) are associated with a decreased risk for Alzheimer disease and other dementias, according to studies presented during the AUA2021 Virtual Experience.

In a study of 26,584 patients with high-risk NMIBC, Dimitrios Makrakis, MD, of the University of Washington in Seattle, and colleagues found that patients with any exposure to BCG had a significant 27% lower risk for Alzheimer disease compared with no exposure after adjusting for age, sex, race, T-stage, and Charlson Comorbidity Index. The risk decreased with increased dosing of BCG. Patients who received 6 or fewer, 7 to 12, and more than 12 doses of BCG had a significant 15%, 27%, and 46% lower risk for Alzheimer disease, respectively, compared with those who received no BCG, the investigators reported in an oral presentation.

The investigators identified study patients using Surveillance, Epidemiology and End Results (SEER)-Medicare linked data. Of the 26,584 patients, 13,477 received BCG. During a median follow-up of 39 months, 2192 patients (8.2%) were diagnosed with Alzheimer disease.

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Sustained neuroinflammation is a key feature of Alzheimer disease. In a mouse model of Alzheimer disease, BCG immunization, which stimulates systemic immune modulation, resulted in improved cognition and reduce inflammation, Dr Makrakis and colleagues noted. Further, previous studies have revealed a lower incidence of Alzheimer disease among patients with bladder cancer treated with BCG.

In a separate study of a racially diverse cohort of 1290 patients with NMIBC receiving treatment at the Montefiore Health System from 1984 to 2020, those who received bladder instillations of BCG had a significant 59% decreased risk for Alzheimer disease and other dementias compared with those who did not, after adjusting for age, race and ethnicity, and comorbidities, Joseph I. Kim, MD, of Albert Einstein College of Medicine in Bronx, New York, and colleagues reported in a poster presentation.

The association was strongest among patients who received both induction and additional maintenance rounds of BCG instillation. These patients had a significant 77% decreased risk for Alzheimer disease and other dementias compared with patients who did not receive BCG. Patients who received BCG induction alone had a nonsignificant 49% decreased risk, Dr Kim and colleagues reported.

The new findings add to those of previous studies demonstrating a link between BCG therapy and a reduced risk for Alzheimer disease in patients with bladder cancer.

For example, in a study of 1371 patients with bladder cancer (1134 men and 237 women) Ofer N. Gofrit, MD, of Hadassah-Hebrew University Medical Center in Jerusalem, Israel, and colleagues found that Alzheimer disease developed in 2.4% of patients treated with BCG and 8.9% of those not treated with BCG during a postoperative follow-up period of 8 years. Compared with BCG-treated patients, those not treated with BCG had a significant 4.8-fold increased risk for Alzheimer disease, Dr Gofrit and colleagues reported in PLoSOne.


Makrakis D, Holt K, Gore JL Grivas P et al. Could BCG treatment in patients (pts) with bladder cancer reduce the incidence of Alzheimer’s disease (AD)? Presented at: AUA2021 Virtual Experience held September 10-13, 2021. Abstract PD47-10

Kim J, hu D, Barry E, et al. Intravesical BCG treatment is inversely associated with the risk of developing Alzheimer’s disease or other dementia among non-muscle-invasive bladder cancer patients. Presented at: AUA2021 Virtual Experience held September 10-13, 2021. Abstract MP16-20.

Gofrit ON, Klein BY, Cohen IR et al. Bacillus Calmette-Guerin (BCG) therapy lowers the incidence of Alzheimer’s disease in bladder cancer patients. PLoS One. 2019;1(11):e0224433 doi:10/1371/journal.pone.0224433