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Should I take the BCG vaccine to reduce my risk of Alzheimer's disease?

Oliver Zolman MD

· Longevity

The following is not medical advice - see my medical disclaimer at www.oliverzolman.com.

In November 2019 an observational study in bladder cancer patients followed for 8 years after receiving bladder injection of BCG vaccine against TB have up to 8 times less risk of developing alzheimers within this followup period

What was the dose and route used?

Intra-vesical immunotherapy with OncoTICE BCG 12.5mg per vial containing 2–8 x 10^8 CFU Tice BCG used

'For study purposes, any dose of BCG qualified the patient in the “BCG group”.'

But its not a randomised controlled trial, just an association, how do we know the BCG vaccine might actually work?
What I find interesting about this non-randomised study is the large effect size and extremely low P value

HR 4.778, 95%CI: 2.837–8.046, p = 4.08x10^-9).

This means there is a 95% chance, if this was a non-majorly flawed randomised controlled trial (but its not), that BCG vaccine would reduce your risk of alzheimer's by 2.837 times compared to those not taking the BCG vaccine.


We can assume the lower bound of the interval of 2.8 as a conservative estimate of the effect size

They were not able to adjust for many confounders such as APOE, APP, CVD, diabetes, head trauma, exercise, sleep problems, nasal trauma, neurological conditions, MS, inflammatory conditions etc...

Also healthy patient physician selection for vaccination bias, lack of dose response due to too low a number of AD cases in bcg group..., and lack of clarity in the ICD10 AD diagnostic coding accuracy - increased by the retrospective nature of the study - AD can be hard to diagnose accurately

Which is why the study is majorly flawed...

But

Because the effect size is so large even at the bottom of the confidence interval (2.8 times risk reduction), after adjusting for all these confounders it feels plausible the lower bound would still be above 1 (no effect).

The study also didn't look at prior BCG vaccination status. So it's a new dose at that age regardless of prior status. That's another confounder follow up trials would have to account for.

But what about the risks of BCG vaccine versus the risks of alzheimer's disease?

Given the low risk of BCG vaccine and the terminal nature of alzheimers, it justifies the use of non randomized studies in populations that have high risk of AD before RCTs.

How is it theoretically predicted to work to prevent alzheimer's?

The mechanism of benefit: a tenfold rise in the serum levels of IL-2 and a fivefold increase in IFNγ were documented at 5–6 weeks after intravesical BCG instillation. This was accompanied by a threefold increase in BCG induced killer-cell activity manifested by peripheral blood mononuclear cells. BCG increases anti-inflammatory cytokines in the brain and therefore reduces neuro-inflammation which is one of the three major pathological features of AD

But would I have to have a catheter inserted into my bladder and have the vaccine injected into my bladder for it to work?

The question remains, does it need to be administered via catheter into the bladder, especially given that this effect size is larger than other, also majorly flawed observational studies.

Maybe the best way of knowing that for sure would be to measure serum cytokines to see if it creates the same level and increase the dose if not getting to those levels.

So

1) Measure as many of the following 3 tests as you can afford and find labs for: IFNy (inteferon gamma), IL-2 (interleukin-2) and natural killer (NK) cell activity)

2) take vaccine orally or intradermally at similar dose to the one used eg 500 million CFUs (this is half way between the 200 - 800 CFU dose they used)

3) Measure at 6 weeks after the dose serum

IL-2 aim for 10x increase

IFNy aim for 5x increase

NKcell activity aim for 3x increase

4) repeat dose of 500 CFU BCG vaccine or higher dose e.g. 800 million CFU if ...

your IL-2 doesn't increase more than 7x from baseline

your IFNgamma doesn't increase more than 3x from baseline

Your NK cell activity doesn't increase more than 2x from baseline

- remeasure again 6 weeks after the booster dose until these levels are achieved

- compare these third set of measurements to the original baseline measurements!

- discuss with your doctor why it might not be working if you are not boosting levels enough

Who should consider this therapy?

The population this would be indicated in would be as that used in this observational study - men or women age 55+ (this is 1 standard deviation below the mean age of the study populations)

But remember: some people may have contraindications to the BCG vaccine, discuss with your doctor.

Also many people may prefer to wait for the BCG vaccine to be tested as a preventive for alzheimer's disease, BUT this may take 5-10 years or may never happen, by which time you may have already developed pre-alzheimer's or alzheimer's.

People at higher risk of alzheimer's might be more inclined to consider this therapy, e.g. those with any family history of dementia or alzheimer's, repeat head trauma, diabetes, heart disease, having 1 or 2 APOE4 gene mutations, other high risk alzheimer's gene mutations.

Or those with head MRI scan, head PET scan, lumbar puncture results or optical coherence tomography (OCT) or blood beta amyloid levels showing signs of pre-alzheimer's or beta amyloid deposits.

Or anyone over age 80, as age alone is a huge risk factor for alzheimer's.

Should I take this study and this blog article to my doctor to request BCG vaccine?

You are welcome to discuss this study and blog article with your doctor or message me to discuss further.

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