Higher-dose flu vaccine associated with nearly 55% lower Alzheimer's risk

A flu shot with a higher antigen dose may provide older adults with an added advantage: a notably lower chance of developing Alzheimer's disease.

In a large study led by UTHealth Houston researchers, adults 65 and older who received a high-dose influenza vaccine were less likely to develop Alzheimer's than those who got the standard-dose shot. Published in Neurology, the findings suggest that the strength of a flu vaccine may matter for more than influenza prevention alone.

The project began with an unexpected discussion between a UTHealth Houston physician and local public health officials. What started as a meeting about earlier vaccine research eventually led scientists to examine whether flu vaccine dose could be linked to different levels of Alzheimer's risk.

A Possible Link Between Flu Vaccination and Alzheimer's

Alzheimer's disease is the most common cause of dementia and a growing public health challenge. More than 7 million Americans ages 65 and older were living with the disease in 2025, or about 1 in 9 people in that age group. That number is expected to more than double by 2050.

Researchers have been studying whether common vaccines may affect the likelihood of developing Alzheimer's. In a 2022 study, a team led by Paul Schulz, MD, reported that flu vaccination was associated with a lower risk of Alzheimer's in adults 65 and older.

Schulz is a professor of neurology at McGovern Medical School at UTHealth Houston and director of the Neurocognitive Disorders Center at UTHealth Houston Neurosciences.

Years after that earlier study, Schulz and his colleagues turned to a more specific question: whether receiving a stronger flu vaccine might be linked to an even greater reduction in Alzheimer's risk.

The idea came from public health officials who had learned about the team's earlier work and invited Schulz to discuss it.

“The public health department had seen our vaccine research and asked if I could come down to talk to them about it,” said Schulz, senior author of the study and the Rick McCord Professor in Neurology and Umphrey Family Professor in Neurodegenerative Diseases at McGovern Medical School. “We went through the findings, and they asked if there was a difference with different dosages; I was confused.”

Why Older Adults Are Offered Stronger Flu Shots

As people age, the immune system becomes less efficient at identifying and fighting infections. That decline can make influenza especially dangerous for older adults.

To help address that risk, the Centers for Disease Control and Prevention recommends high-dose influenza vaccines as a preferred option for adults 65 and older. These shots contain four times as much influenza antigen as standard-dose vaccines. Antigens are the parts of a vaccine that prompt the immune system to recognize and respond to a virus.

The higher dose is meant to trigger a stronger immune response in older adults, whose bodies may not react as effectively to conventional vaccines.

Schulz said he had not realized that the stronger version was available.

“I was stunned that, as a physician, I didn't know a higher dose was offered,” Schulz said.

Annual flu vaccination is recommended for everyone, but avoiding influenza is especially important for people with Alzheimer's disease. Flu infections and related complications can be particularly serious for individuals already dealing with cognitive impairment.

Before 2022, the CDC did not prefer one injectable flu vaccine over another for people 65 and older. The guidance focused instead on getting vaccinated each year, regardless of formulation.

Earlier UTHealth Houston research had already linked inactivated influenza vaccines, which use viruses that cannot cause influenza infection, with a 40% lower risk of developing Alzheimer's disease. Still, it was not known whether a higher dose might provide additional benefit.

Another practical factor made the question especially relevant. As the older population grows, demand for high-dose flu vaccines can exceed supply, leaving some seniors to receive standard-dose shots instead.

That difference gave researchers a chance to compare Alzheimer's outcomes among older adults who received different formulations.

“So we started looking, and sure enough, we were able to put together thousands and thousands of people over the age of 65 who got the high- or low-dose vaccine. They're more at risk for Alzheimer's than anybody else, of course, because it's age-related and we could look at high-dose versus low-dose and see if there was a difference,” Schulz said.

Nearly 200,000 Adults Showed a Clear Difference

To explore the possible connection, the research team analyzed data from nearly 200,000 men and women ages 65 and older.

The results showed that people who received high-dose influenza vaccines had a significantly lower risk of developing Alzheimer's disease than those given the standard-dose version.

According to the researchers, standard-dose influenza vaccination was associated with a 40% reduction in Alzheimer's risk, while high-dose vaccination was linked to a reduction of nearly 55%.

The association was especially strong among women, who appeared to gain a larger reduction in Alzheimer's risk from the stronger vaccine.

The findings add to growing evidence that influenza vaccination may be related to brain health. They also raise questions about whether the immune response sparked by vaccination could affect biological processes involved in Alzheimer's disease.

Even so, the study shows an association rather than proving cause and effect. More research is needed to determine whether high-dose flu vaccination directly lowers Alzheimer's risk and to understand the biological mechanisms that may explain the connection.

What the Findings May Mean for Prevention

With Alzheimer's affecting millions of Americans and cases expected to rise sharply in the years ahead, researchers continue to look for practical ways to lower risk.

The idea that an existing vaccine could offer benefits beyond influenza prevention is especially noteworthy. Unlike a new treatment, flu vaccination is already widely used, and high-dose formulations are designed specifically for older adults.

The new findings suggest that vaccine dosage may deserve attention in future research on the relationship between the immune system and Alzheimer's disease.

For now, the study offers another reason to examine the possible benefits of influenza vaccination while underscoring the need for further research before drawing conclusions about Alzheimer's prevention.

Study Team and Contributors

Avram Samuel Bukhbinder, MD, a graduate of McGovern Medical School who is now a clinical fellow in neurology at Massachusetts General Hospital and Harvard University, was a corresponding author of the study.

Schulz is also a faculty member of The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences.

Other contributors from McGovern Medical School included Elizabeth He, visiting scholar in the Department of Neurology; Kristofer Harris, MPH, research coordinator in the Department of Neurology; Mya Rodriguez, graduate research assistant in the Department of Neurology; Kamal Phelps, MD, an alumnus of the Department of Neurology; Jenna Thomas; Gabriela Cruz, MD, resident in the Department of Neurology; and Lauren Jhin.

Researchers from the McWilliams School of Biomedical Informatics at UTHealth Houston also took part. They included Xiaoqian Jiang, PhD, associate vice president for medical AI, chair of the Department of Health Data Science and Artificial Intelligence, and Christopher Sarofim Family Professor in Biomedical Informatics and Bioengineering; Yejin Kim, PhD, assistant professor in the Department of Health Data Science and Artificial Intelligence; Luyao Chen, researcher; and Yaobin Ling, PhD, postdoctoral research fellow.