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Is There a Link Between Alzheimer’s Disease and the Flu Shot?

Is There a Link Between Alzheimer’s Disease and the Flu Shot?

Flu season has arrived. During the 2017-2018 season, over 79,000 people in the United States died from the flu [1]. People over age 65 are at the greatest risk for flu-related complications, accounting for 70% of hospitalizations and 90% of flu-related mortality last year. The Centers for Disease Control and Prevention (CDC) recommends that everyone 6 months of age and older get a flu vaccine every season. But, for one reason or another, many people choose not to get vaccinated. To help you make an informed decision this season, let's review the myths surrounding flu vaccines and the scientific evidence behind how flu vaccines may be associated with better brain health.

MYTH: Getting the flu vaccine increases the risk for Alzheimer's disease.

WHAT THE EVIDENCE SAYS: There is no peer-reviewed scientific evidence supporting this claim, instead, there is evidence to support an association between getting the flu shot and a decreased risk for dementia.

A study of approximately 4,000 people over age 65 found that people with previous exposure to vaccines for diphtheria, tetanus, polio, and the flu had a decreased risk for Alzheimer's disease [2]. Another study of nearly 12,000 people with chronic kidney disease found that flu vaccinated people had a 30-40% lower risk of dementia than their unvaccinated counterparts [3]. Furthermore, the study showed that people who got their flu shots more regularly had greater benefit in lowering their risk for dementia. There is also no evidence that getting the flu shot worsens cognitive decline in people with Alzheimer's disease. Meanwhile, individuals with dementia who get the flu are at 1.5 times increased risk for flu-related mortality [4]. Although these observational studies cannot distinguish cause from effect, they suggest that getting the annual flu shot may be one factor in maintaining a healthy lifestyle associated with promoting lifelong brain health.

MYTH: The flu vaccine contains potential toxins.

WHAT THE EVIDENCE SAYS: Currently available flu vaccines are aluminum-free and over 80% of flu vaccines today contain no mercury at all. Some flu vaccines contain a tiny amount of formaldehyde that is less than 1% of the amount naturally found in people and is safely cleared from the body.

Mercury: The type of mercury used in vaccines is rapidly removed from the body and is not the kind associated with toxicity.

There are two major types of mercury in the environment: methyl mercury and ethyl mercury. Methyl mercury accumulates in the body and is very toxic at high levels, whereas ethyl mercury is safely removed from the body, which prevents it from causing toxicity. The EPA guidelines to limit consumption of some large fish, such as tuna, swordfish and shark, are based on the accumulation of methyl mercury in the tissues of these fish [5]. Some vaccines contain an extremely small amount of ethyl mercury in the form of a preservative called thimerosal [6], which helps to prevent the growth of bacteria and fungi in the vaccine when it is stored in multi-use vials [7]. Single-dose flu vaccines do not contain thimerosal, and more than 80% of the projected vaccine supply for the 2018-2019 season is thimerosal-free [8]. Additional information about the thimerosal content of available seasonal vaccines can be found on the FDA and CDC websites.

Aluminum: Some vaccines use a safe amount of aluminum (i.e. less than the level of aluminum exposure found in two glasses of juice [9]) as an additive to boost the ability of the immune system to effectively respond to the vaccine. However, none of the flu vaccines available for the 2018-2019 flu season contain aluminum [10].  

Formaldehyde: The tiny amount of formaldehyde contained in some flu vaccines is rapidly and safely cleared from the body. Several types of flu vaccines, including the nasal spray formulation and the new cell culture-based flu vaccines, do not contain any formaldehyde.

Our bodies naturally produce small quantities of formaldehyde that can be easily cleared without causing toxicity [11], thus exposure to levels below the naturally produced amount is considered safe. Formaldehyde is used during the vaccine making process to kill the virus for vaccines that contain inactivated virus, and the vast majority of it is removed before the vaccine is packaged for distribution [12]. The level of remaining formaldehyde in vaccines ranges from less than 0.005 to 0.1 mg. These levels are less than 1% of the amount normally circulating in our body (e.g., 11 mg for the average adult female [13]) as a byproduct of metabolism, and thus can be safely cleared from our body [11]

MYTH: Everyone gets the same flu vaccine.

WHAT THE EVIDENCE SAYS: There are many options for getting a flu vaccine, and some types may be better suited for certain people than for others.

Nasal spray vs. flu shot: The nasal spray contains live weakened virus, while the flu shot contains inactivated virus. The nasal spray is approved for use in people from ages 2-49 [14], but should not be used by pregnant women, children taking aspirin therapy, or children with asthma. In previous years, the nasal spray was less effective than the flu shot, but there is a new formulation available for the 2018-2019 season [14], which is expected to make the spray a good alternative for those unable to tolerate the shot.

Trivalent vs. Quadrivalent: Trivalent vaccines protect against two influenza A viruses and one influenza B virus, while the quadrivalent vaccines protect against two influenza A and two influenza B viruses [15]. Approximately three-quarters of the available vaccine for the 2018-2019 season is in the quadrivalent form.

Single-dose vs. Multi-dose vials: Single-dose vaccines are generally one-time use syringes pre-filled with the vaccine, while multi-dose vials contain larger quantities of vaccine and can be used to vaccinate multiple people [8]. To ensure their sterility, small amounts of the preservative thimerosal are used in multi-dose vaccine vials.

Egg-based vs. Cell culture-based: Traditionally flu vaccines have been produced in chicken eggs and could not be used by people with egg allergies. The egg-grown viruses sometimes develop egg-adapted changes, which could affect their ability to make the proper immune response in people [16]. Cell culture-based vaccines are grown in cells, and can be used by people with egg allergies. Flucelax, which is the currently available FDA-approved cell-culture based flu vaccine, is preservative-free in the single-dose form.

Options for people over 65: Most people can develop a strong immune response to the flu virus in the traditional vaccine. However, individuals over the age of 65 generally have weaker immune systems and require special formulations of the vaccine to develop protective immunity. Two formulations are available, and can also be beneficial for people younger than 65 with compromised immune systems.

Fluad uses an additive called MF59 to boost the immune response to the flu virus [17]. MF59 is made from squalene oil, which is a natural substance found in plants and animals, and has a good safety record.

The Fluzone High-Dose vaccine contains four times as much flu virus antigen as the standard dose vaccine [18]. This higher level should make it easier for the immune system to develop a sufficient response to the flu virus. In a randomized clinical trial, the high-dose vaccine was found to be 24.2% more effective for flu prevention than the standard dose in people over age 65 [19].


There are many different types of flu vaccines. The flu vaccine is safe for most people, however, anyone who has had Guillain-Barre syndrome (a rare neurological disorder) or a severe allergic reaction in response to a prior flu shot should avoid getting the flu vaccine. Consult your doctor to help determine the best type of flu shot for you. A list of which types and formulations of vaccines are available in your area can be found on the HealthMap Vaccine Finder website.


  1. Centers for Disease Control and Prevention (2018) Estimated Influenza Illnesses, Medical visits, Hospitalizations, and Deaths in the United States — 2017–2018 influenza season.
  2. Verreault R, Laurin D, Lindsay J et al. (2001) Past exposure to vaccines and subsequent risk of Alzheimer's disease. CMAJ : Canadian Medical Association journal = journal de l'Association medical canadienne 165, 1495-1498.
  3. Liu J-C, Hsu Y-P, Kao P-F et al. (2016) Influenza Vaccination Reduces Dementia Risk in Chronic Kidney Disease Patients: A Population-Based Cohort Study. Medicine 95, e2868-e2868.
  4. Naumova EN, Parisi SM, Castronovo D et al. (2009) Pneumonia and Influenza Hospitalizations in Elderly People with Dementia. Journal of the American Geriatrics Society 57, 2192-2199.
  5. Environmental Protection Agency (2018) Guidelines for Eating Fish that Contain Mercury.
  6. Dórea JG, Farina M, Rocha JBT (2013) Toxicity of ethylmercury (and Thimerosal): a comparison with methyl mercury. Journal of Applied Toxicology 33, 700-711.
  7. Centers for Disease Control and Prevention (2015) Thimerosal in Vaccines.
  8. Centers for Disease Control and Prevention (2018) Seasonal Influenza Vaccine Supply for the U.S. 2018-2019 Influenza Season.
  9. Stahl T, Taschan H, Brunn H (2011) Aluminium content of selected foods and food products. Environmental Sciences Europe 23, 37.
  10. Centers for Disease Control and Prevention (2018) Adjuvants help vaccines work better.
  11. Burgos-Barragan G, Wit N, Meiser J et al. (2017) Mammals divert endogenous genotoxic formaldehyde into one-carbon metabolism. Nature 548, 549.
  12. Centers for Disease Control and Prevention (2018) Ingredients of Vaccines - Fact Sheet.
  13. Children's Hosptial of Philadelphia (2018) Vaccine Ingredients – Formaldehyde.
  14. Centers for Disease Control and Prevention (2018) Live Attenuated Influenza Vaccine [LAIV] (The Nasal Spray Flu Vaccine).
  15. Centers for Disease Control and Prevention (2018) Quadrivalent Influenza Vaccine.
  16. Centers for Disease Control and Prevention (2018) Cell-based Flu vaccines.
  17. Centers for Disease Control and Prevention (2018) Flu Vaccine With Adjuvant.
  18. Centers for Disease Control and Prevention (2018) Fluzone High-Dose Seasonal Influenza Vaccine.
  19. DiazGranados CA, Dunning AJ, Kimmel M et al. (2014) Efficacy of High-Dose versus Standard-Dose Influenza Vaccine in Older Adults. New England Journal of Medicine 371, 635-645.

Betsy Mills, PhD, is Senior Program Manager of Aging and Alzheimer’s Prevention at the Alzheimer’s Drug Discovery Foundation. She earned her doctorate in neuroscience at Johns Hopkins University School of Medicine, where she studied the role of glial cells in the optic nerve and their contribution to neurodegeneration in glaucoma; and completed a Postdoctoral fellowship at the University of Michigan, where she worked to uncover genes that could promote retina regeneration. Dr. Mills has a strong passion for community outreach, and served as program presenter with the Michigan Great Lakes Chapter of the Alzheimer's Association to promote dementia awareness.

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