A new study published in the journal Nature Aging adds to growing evidence that serious infections, including influenza, herpes and respiratory infections, are linked to rapid brain shrinkage and an increased risk of dementia years later.

This research also suggests biological factors that may contribute to neurodegenerative diseases.

How does dementia relate to infection?

The Washington Post said the current study is “a leap forward from previous studies that have linked infection to the likelihood of Alzheimer’s disease” and provides a “useful data set,” according to Rudy Tanzi, a professor of neurology at Harvard Medical School and director of the McCance Center for Brain Health at Massachusetts General Hospital.

Recent studies have also shown that flu shots and shingles vaccines reduce the risk of dementia later in life in those who receive them. Serious infections have also been linked to subsequent strokes and heart attacks.

“A vaccine would be the best protection against both acute infection and these post-infection effects,” said Kristen Funk, an assistant professor of biological sciences at the University of North Carolina at Charlotte who studies neuroinflammation in neuroinfectious and neurodegenerative diseases.

“The idea that infections can affect brain health for some people is understandable, especially those who have experienced infections,” said Keenan Walker, a researcher and director of the Multimodality Imaging Unit for Neurodegenerative Diseases at the National Institute on Aging.

Even minor infections can change the way we think and behave. More severe infections can cause delirium in the short term, which is linked to long-term cognitive problems, Walker says. “Big infections, big immune responses are not good for the brain,” he says.

The hypothesis that infections might play a role in neurodegenerative diseases has existed, albeit largely on the sidelines, Walker said. That changed with the COVID-19 pandemic and evidence of the long-term cognitive effects of infection, which has increased interest in the field.

Growing evidence suggests the link “doesn’t appear to be specific to any particular type of infection, whether bacterial or viral,” said Walker, a co-author of the study.

The biological link between the brain and infection

Walker and colleagues relied on data from the Baltimore Longitudinal Study of Aging, one of the oldest studies of aging in the United States.

They also tracked brain volume changes in 982 cognitively normal adults, with or without a history of infection, using repeated brain imaging, starting in 2009. About 43% of participants had no history of infection.

Of the 15 infections studied, six – influenza, herpes, respiratory infections and skin infections – were associated with faster brain volume loss. The brain shrinkage was particularly pronounced in the temporal lobe, an area that includes the hippocampus, which is important for memory and has been linked to Alzheimer's disease.

“They actually found that there was a spectrum of infections associated with this brain atrophy, associated with this cognitive decline,” said Funk, who was not involved in the study.

Most infections associated with brain atrophy appear to be risk factors for dementia, according to researchers' analysis of UK Biobank data of 495,896 subjects and a Finnish dataset of 273,132 subjects.

They found that a history of infection was associated with a higher risk of developing Alzheimer's disease years later. The risk increased even more for vascular dementia, the second most common dementia diagnosis after Alzheimer's disease and caused by restricted blood flow to the brain.

In general, infections are associated with an increase in disease-causing proteins and a decrease in protective proteins. This study “sheds light on potential biological pathways that lead to increased risk of dementia following severe infections,” said Charlotte Warren-Gash, professor of epidemiology at the London School of Hygiene and Tropical Medicine, who was not involved in the study.

A better understanding of the proteins involved may one day lead to better targeting of the immune system.

Reducing the risk of serious infection remains important for both short-term and long-term health, experts say. Vaccination is the best way to prevent serious infection.

Additionally, the CDC recommends two doses of the shingles vaccine for everyone age 50 and older. Other health measures such as wearing a mask and washing your hands properly also help reduce the risk of infection.