A vial of the BCG vaccine sits on top of a pack of the remaining vialsShare on Pinterest
Vials of the BCG vaccine are seen in the trial clinic at Sir Charles Gairdner Hospital on April 20, 2020, in Perth, Australia. Paul Kane/Getty Images
  • The Bacillus Calmette-Guerin (BCG) vaccine has been in use for more than 80 years to combat tuberculosis.
  • In the 1970s, it was found to be an effective immunotherapy treatment for early-stage bladder cancers.
  • Since then, it has become one of the standard treatments for this cancer, administered directly into the bladder.
  • A study has now found that it may have a beneficial side effect — people receiving this therapy seem to have a reduced risk of developing dementia.

According to the Centers for Disease Control and Prevention (CDC), each year around 57,000 men and 18,000 women are diagnosed with bladder cancer in the United States. And each year, about 12,000 men and 4,700 women die from the disease in the U.S.

The risk of bladder cancer increases with age. Around 90% of diagnoses are in people aged over 55, and the average age of diagnosis is 73. Smoking tobacco greatly increases the risk, with smokers at least three times more likely than nonsmokers to develop bladder cancer.

At the time of diagnosis, half of all bladder cancers are noninvasive, with cancer cells only in the inner layer of the bladder wall. A common therapy for this early-stage cancer is intravesical immunotherapy with Bacillus Calmette-Guerin (BCG).

BCG is a non-pathogenic bacterium similar to that which causes tuberculosis (TB). It was developed in 1921 and has been used as a vaccination against TB for more than 80 years. Although less frequently used now than in the past to protect against TB in developed countries, it is still widely used in countries where TB is endemic.

However, since the 1970s, it has been used successfully to treat early-stage bladder cancer. When a catheter introduces BCG via the bladder, it induces immune cells to attack the cancer cells.

Now, a new study has found that this treatment is associated with a beneficial side effect. Patients receiving the treatment had a reduced risk of dementia and death compared with patients receiving alternative treatments.

The study is published in JAMA Network Open.

“This is a really interesting study and encouraging approach to an additional potential treatment mechanism for dementia.”­
— Dr. Emer MacSweeney, CEO and consultant neuroradiologist at Re:Cognition Health, speaking to Medical News Today

Dr. Heather Snyder, Ph.D., vice president of medical and scientific relations at the Alzheimer’s Association (which funded the study), commented:

“The researchers found that, in a large population of older adults with bladder cancer, BCG vaccination was associated with a lower rate and risk of dementia. This is in line with what we’ve seen in previous research connecting BCG vaccination and cognition.”

“The rationale is this vaccine, which induces innate immune training, may help reduce brain inflammation — a driving contributor to Alzheimer’s,” she said.

At the start, all those in the study were ages 50 or over, with a mean age of 70.3 years, and were diagnosed with non-muscle-invasive bladder cancer (NMIBC). All participants had undergone initial transurethral resection of bladder tumor (TURBT) following diagnosis.

A total of 6,467 people with NMIBC were included in this 15-year follow-up study. Of these, 3,388 people had received BCG vaccine treatment, and 3,079 had not. The BCG and control groups were similar in sex, age, race, ethnicity, and comorbidities.

During the follow-up, the researchers recorded dementia where participants had an ICD-9 or ICD-10 dementia diagnosis or were prescribed drugs used exclusively for dementia treatment.

In the BCG group, 202 individuals developed dementia, and in the control group, 262 developed the condition. Overall, those treated with BCG had a 20% lower risk of Alzheimer’s disease and related dementias.

The effect was most pronounced in participants ages 70 and over, where there was an even greater difference in the risk of dementia between the BCG and non-BCG groups. There was no association in the younger subcohort.

The researchers also found that those in the BCG group had a 25% lower risk of death from all causes during follow-up than those in the control group.

“A 20% reduced risk of Alzheimer’s sounds modest at first, but for those families spared the disaster that is living through Alzheimer’s, the value is priceless.”
— Dr. David MerrillPh.D., geriatric psychiatrist and director of the Pacific Neuroscience Institute’s Pacific Brain Health Center in Santa Monica, California, speaking to MNT

Dr. Merrill told MNT that the study does not prove a causal link between the BCG vaccine and a reduced risk of Alzheimer’s.

“If we can better understand which patients will have their brains protected from Alzheimer’s through BCG vaccination, then we can target delivering the vaccine to those susceptible individuals,” he said.

“Perhaps we can identify one or more immune markers that predict a protective effect of the vaccination. For those individuals who aren’t afforded protection by the BCG vaccine, we will need to figure out what factors are causing their development of Alzheimer’s,” he added.

The authors note several limitations of this observational study, including that using the diagnostic codes and medications may underestimate the incidence of dementia.

They also note that frailer patients are less likely to receive BCG treatment and are more likely to develop dementia, possibly increasing the likelihood of those in the control group receiving a dementia diagnosis.

“Limitations include the study’s design, which can only demonstrate an association, not causation. Additionally, this study was done in a largely white, male population. Research in more diverse populations is needed to determine if those same associations exist for all individuals.”
— Dr. Heather Snyder

Studies have shown that many routine adult vaccinations are associated with a decreased risk of dementia. Although this could be due to socio-economic factors — people who follow a lifestyle that is linked to lower dementia risk are more likely to keep their vaccinations up to date — there are possible physiological reasons for the link.

One study suggests that vaccinations might train the immune system to respond to threats in a more regulated manner, thereby reducing the inflammation and oxidative stress that contribute to the development of dementia.

Dr. MacSweeney outlined how the BCG vaccine might reduce dementia risk:

“As BCG treatment stimulates the immune system, a broader effect on overall health might also be expected. We know a healthy immune system is important for good brain function, and there is evidence to suggest that chronic inflammation and immune dysregulation may contribute to the development of Alzheimer’s disease.”

However, the authors of this study do point out that there is not yet enough evidence to prove a causative link, and call for ‘well-designed interventional trials” to try and clarify the link.

“Building on this work with the help of funding from the Alzheimer’s Association Part the Cloud program, this research group is also actively conducting an early phase clinical trial to evaluate the impact of the BCG vaccine on inflammatory markers in individuals with mild cognitive impairment or early-stage Alzheimer’s. This trial is an important next step to determine whether BCG vaccination has direct impacts on brain inflammation in Alzheimer’s.”
— Dr. Heather Snyder

This finding is certainly a positive step towards effective dementia prevention and treatment. Still, there remains work to be done in understanding how it works and who it would benefit most.