Prior vaccinations may have AD risk-lowering benefit

Getting vaccinated against tetanus, diphtheria, shingles, and pneumonia appears to help lower the risk of Alzheimer's disease (AD) in older people, according to a claims-based cohort study involving more than 1.5 million individuals.

Propensity-score matching analysis showed that people who received the tetanus and diphtheria (with or without pertussis [Tdap/Td]) vaccine were 30 percent less likely than their unvaccinated counterparts to have AD over an 8-year follow-up period (7.2 percent vs 10.2 percent; relative risk [RR], 0.70, 95 percent confidence interval [CI], 0.68–0.72; absolute risk reduction [ARR], 0.03, 95 percent CI, 0.02–0.03). [J Alzheimers Dis 2023;doi:10.3233/JAD-221231]

The same was true for individuals who were vaccinated against herpes zoster (HZ), with the risk of developing AD being 25 percent lower than in their unvaccinated peers (8.1 percent vs 10.7 percent; RR, 0.75, 95 percent CI, 0.73–0.76; ARR, 0.02, 95 percent CI, 0.02–0.02).

Finally, those who received the pneumococcal vaccine had a 27-percent reduced risk of AD compared with those who were unvaccinated (7.92 percent vs 10.9 percent; RR, 0.73, 95 percent CI, 0.71–0.74; ARR, 0.02, 95 percent CI, 0.02–0.03).

These findings are in line with a those of a previous study by the same research team, who found that receiving at least one shot of influenza vaccine was associated with a 40-percent reduction in the risk of AD. [J Alzheimers Dis 2022;88:1061-1074]

“We were wondering whether the influenza finding was specific to the flu vaccine, [and the present data] revealed that several additional adult vaccines were also associated with a reduction in the risk of Alzheimer’s,” according to senior study author Prof Paul Schulz from McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, US.

“We and others hypothesize that the immune system is responsible for causing brain cell dysfunction in Alzheimer’s. The findings suggest to us that vaccination is having a more general effect on the immune system that is reducing the risk for developing Alzheimer’s,” Schulz added.

A combination of mechanisms

How the risk of AD drops following vaccination against certain diseases may be explained by a combination of mechanisms, said study co-author Dr Avram Bukhbinder of the University of Texas Health Science Center at Houston, Houston, Texas, US.

“Vaccines may change how the immune system responds to the buildup of toxic proteins that contribute to AD, such as by enhancing the efficiency of immune cells at clearing the toxic proteins or by ‘honing’ the immune response to these proteins so that ‘collateral damage’ to nearby healthy brain cells is decreased. Of course, these vaccines protect against infections like shingles, which can contribute to neuroinflammation,” Bukhbinder pointed out.

That being said, Bukhbinder, along with Schulz and the others in the team, stressed the importance of having ready access to routine adult vaccinations and being aware of all their benefits for patients.

“The value of vaccination, as we have demonstrated, goes beyond preventing infection or severe disease from that infection. In fact, there are multiple nonspecific potential benefits of vaccination such as improving asthma severity, AD prevention, and use as an adjuvant cancer therapy [even though it is administered through a nontraditional route], among others,” they said. [Int J Epidemiol 2010;39:469-486; J Alzheimers Dis 2022;88:1061-1074; Front Immunol 2022;13:872542; Appl Microbiol Biotechnol 2019;103:7903-7916; Urol Oncol 2021;39:121-129]

The researchers believe that discussing the added nonspecific advantages of vaccination with patients may help overcome vaccine hesitancy.

“Clinicians may be able to convince hesitant patients that the benefits of vaccination with one of the routine adult vaccinations outweigh the risks,” they said.

The study involved 1,651,991 participants, of whom 122,777 received Tdap/Td vaccinations, 212,417 received herpes zoster vaccinations, and 286,504 received pneumococcus vaccinations.