During a viral pandemic, everything to do with vaccination is au courant. At this week’s virtual Alzheimer’s Association International Conference, two reports drew attention by turning on its head the field’s emerging research trend suggesting that systemic infections could help trigger Alzheimer’s pathology in the brain. If that is true, the new studies asked, does warding off infection lower a person’s Alzheimer’s risk? Some initial data presented at AAIC hint that it might. Analyzing large population datasets, researchers found that vaccination against both influenza and pneumococci was associated with a lower risk of subsequent Alzheimer’s disease. Alas, the data are correlational, hence it is unclear if the shots themselves are protective, or if people who choose vaccination engage in other healthy behaviors that make them less likely to get Alzheimer’s.

  • People who get flu shots appear to be at lower risk of Alzheimer’s.
  • The same goes for pneumonia vaccination.
  • It is unclear if the shots are themselves protective, or correlate with other health behaviors.

“This research, while early, calls for further studies in large, diverse clinical trials to inform whether vaccinations as a public health strategy decrease our risk for developing dementia as we age,” Maria Carrillo of the Alzheimer’s Association said in a press release.

Even if the effect on AD risk is indirect, vaccinations may improve the overall health of Alzheimer’s patients. Another study found that people with AD are twice as likely to die after a serious infection as are cognitively healthy people, suggesting they have a heightened vulnerability and might benefit more from vaccination than same-age controls.

One of the most common vaccinations is the annual flu shot. About 45 percent of American adults got the vaccine in the 2018–19 flu season, according to the Centers for Disease Control and Prevention. Some previous studies have associated past flu vaccinations with a lower risk of dementia (Verreault et al., 2001; Liu et al., 2016). 

To investigate further, Albert Amran, working in the lab of Paul Schulz at the University of Texas Health Science Center, Houston, assembled an ad hoc cohort from a medical records database. For the analysis presented at AAIC, they selected 9,066 participants over age 60, and matched Alzheimer’s patients with controls who had similar demographics. They also matched participants by medical history and access to care, to try to control for confounding effect due to better health habits. In this dataset, people who had received even one flu shot in years prior were 17 percent less likely to have AD than the unvaccinated group. Among the vaccinated subset, receiving yearly flu shots in the past dropped the odds of AD by another 13 percent. In addition, age at first vaccination mattered, with a one-year delay boosting the risk of later developing AD by 9 percent. Altogether, vaccinated people between the ages of 75 and 84 ran a 6 percent lower risk of developing Alzheimer’s over the next 16 years than their unvaccinated peers, the authors calculated.

“We hypothesize that vaccination may modulate neuroinflammation, resulting in a reduction of AD pathogenesis,” the authors wrote to Alzforum, noting that their final paper will include data on nearly 40,000 people.

In another study, flu vaccines by themselves were not protective, but pneumonia vaccines, or a combination of both, were. Svetlana Ukraintseva and colleagues at Duke University analyzed data from 5,146 participants in the NIH’s Cardiovascular Health Study. Half the cohort received one or more flu shots between the ages of 65 and 75, while 37 percent got vaccinated against pneumonia in the same time period. After the age of 75, 297 people, or about 6 percent of the cohort, developed AD.

People who got the pneumonia vaccine were 30 percent less likely to develop AD, after adjusting for sex, race, birth cohort, education, and smoking. Receiving more vaccinations seemed to bump up the protection, with a higher total number of flu and pneumonia vaccinations correlating with a 12 percent lower risk.

Intriguingly, the protection appeared stronger in people who did not carry the TOMM40 AD risk allele. This allele has been linked by some researchers to an earlier age of onset, although subsequent studies did not support the finding (Nov 2009 conference newsJul 2010 conference news; Aug 2011 news). Among noncarriers of the proposed risk allele, receiving any pneumococcal vaccination was associated with 38 percent less risk of AD, while having a higher number of flu and pneumonia vaccinations dropped risk 15 percent in noncarriers.

Other researchers were divided over what the findings might mean. Rudolph Tanzi at Massachusetts General Hospital, Boston, speculated that systemic infections that spill into the brain could trigger β-amyloidosis, as has been demonstrated in model systems (May 2016 news; Jun 2018 news). Todd Golde at the University of Florida, Gainesville, said this mechanism could make sense given what is known about the immune system and AD, but cautioned that the current evidence is too weak to draw any conclusions about causation. “Inferring causation from [epidemiological] studies has often led the AD field down rabbit holes,” Golde wrote to Alzforum. Nonetheless, he noted that nearly everyone should receive influenza and pneumonia vaccinations anyway, due to their other beneficial health effects.

Another study indicated a need for this type of protection in elderly people with dementia. Janet Janbek at the Danish Dementia Research Centre in Rigshospitalet analyzed national health registry data on 1,496,436 people older than 65. She found that being admitted to a hospital with an infection tripled their death rate in general, but if the infected person also had dementia, their risk of dying was 6.5 times higher than that of non-demented controls.

However, other data cast doubt on the efficacy of vaccination in older populations. Lindsey Nakakogue at Pontifical Catholic University of Paraná in Londrina, Brazil, reported at AAIC that pneumococcal vaccination did not improve the odds of surviving pneumonia in a group of 510 people with dementia in their 80s. Slightly less than half received the vaccination, and both groups were equally likely to get pneumonia and to die from it.—Madolyn Bowman Rogers

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References

News Citations

  1. Las Vegas: AD, Risk, ApoE—Tomm40 No Tomfoolery
  2. Honolulu: Tomm40 Reported to Track With Brain Atrophy, Cognition
  3. Large Study Questions Tomm40’s Effect on AD Age of Onset
  4. Like a Tiny Spider-Man, Aβ May Fight Infection by Cocooning Microbes
  5. Herpes Triggers Amyloid—Could This Virus Fuel Alzheimer’s?

Paper Citations

  1. . Past exposure to vaccines and subsequent risk of Alzheimer's disease. CMAJ. 2001 Nov 27;165(11):1495-8. PubMed.
  2. . Influenza Vaccination Reduces Dementia Risk in Chronic Kidney Disease Patients: A Population-Based Cohort Study. Medicine (Baltimore). 2016 Mar;95(9):e2868. PubMed.

External Citations

  1. Centers for Disease Control and Prevention
  2. Cardiovascular Health Study

Further Reading