Virus That Causes Cold Sores Linked to Increased Risk of Alzheimer’s Disease

A new study has found that herpes simplex 1 (HSV-1)—the common virus behind cold sores—may be linked to the development of Alzheimer’s disease. The report, published in BMJ Open on May 20, found that people who take antiviral medications also have a lower risk of developing dementia later in life.

Scientists are eager to understand what causes neurodegenerative diseases, which are becoming more prevalent around the world. The World Health Organization estimates that about 57 million people had dementia worldwide in 2021 and that about 10 million new cases are diagnosed each year. While there are treatments that can help manage the symptoms and slow disease progression, there is no cure for Alzheimer’s disease.

Prior research suggests herpes viruses may play a role in the development of Alzheimer’s disease; however, the data have been mixed. The new findings, which were sponsored by biopharmaceutical company Gilead Sciences, Inc., “add to a growing body of evidence dating back to the 70s that viruses like HSV-1, and our body’s responses to them, could contribute to developing Alzheimer’s,” said Kimberly Idoko, MD, a neurologist and children’s rights attorney.

To understand how HSV-1 may be related to Alzheimer’s disease, the researchers looked at a large pool of data from U.S. administrative claims filed between 2006 and 2021. They then matched individuals diagnosed with Alzheimer’s disease to a group without any history of neurological conditions, taking into account factors like age, sex, and geographic location. A total of 344,628 pairs emerged.

The research team found that:

• 1,507 of those with Alzheimer’s disease (0.5%) had been diagnosed with HSV-1 compared to just 828 (0.25%) of those in the comparison group who had no history of neurological disease.
• The likelihood of having been diagnosed with HSV-1 was 80% greater in the group that had Alzheimer’s, even when adjusting for various risk factors.
• That risk increased with older patients, with those over 75 facing the highest risk of having Alzheimer’s disease and a previous HSV-1 diagnosis.

“The findings from the current study, utilizing real-world data, are consistent with previous studies suggesting that the potential neurodegenerative impact of HSV-1 becomes more apparent with age,” Gilead Sciences told Health in a statement.

On top of that, being treated with antiviral medications appeared to cut the risk of Alzheimer’s disease. Of the 2,330 people who’d been diagnosed with HSV-1, 931 (40%) had taken antiherpetic medication like acyclovir, valacyclovir, or famciclovir. They had a 17% lower risk of Alzheimer’s disease compared to those who didn’t take antivirals.

The study “provides indirect but compelling evidence that reducing the amount of free herpesvirus in the body may reduce the risk of Alzheimer’s disease diagnosis,” said David Martinez, PhD, an assistant professor of immunobiology and microbial pathogenesis at Yale School of Medicine.

It’s important to note that the study does not claim that HSV-1 causes Alzheimer’s. Instead, it found a link between the two. “We still don’t fully understand how these herpesvirus infections that lie dormant and periodically reactivate trigger Alzheimer’s disease,” Martinez told Health.

But scientists have a few theories. They believe that HSV-1 infections can lead to specific dementia contributors, including:

• Inflammation in the brain (neuroinflammation). This inflammation may set the stage for Alzheimer’s disease, research shows. But that inflammation doesn’t end when the acute infection clears. “Herpes viruses hide out in your nerves and they sometimes ‘come out’ from stressors such as immunodeficiency, or lack of sleep, or other infections, or a blow to the head,” Martinez said. As such, these dormant viruses can repeatedly activate throughout your life, creating new waves of inflammation years after the original infection. “When HSV-11 reactivates, it can trigger the brain’s immune cells to become overly active, creating inflammation in the brain,” Idoko told Health.
• An accumulation of toxic proteins. The body produces proteins like amyloid-beta as a defense. They “then directly damage brain cells,” Idoko said.
• Synaptic dysfunction. This refers to a disruption in the ability of nerve cells to communicate with one another.

HSV-1 is common, with over two-thirds of the global population getting an infection at some point. It is transmitted through contact with an infected person’s saliva or skin lesions—but, of course, not everyone who’s exposed gets dementia.

As for why only some people who get HSV-1 develop Alzheimer’s disease, Idoko suspects genetics play a role. As the study authors noted, people who are carriers of the genetic variant ApoE ε4 allele, which is a known risk factor for Alzheimer’s disease, are more susceptible to HSV-1. Other factors, including the frequency and severity of reactivations, could increase some people’s risk, Idoko said. And lifestyle habits—such as chronic stress, poor sleep hygiene, or poor diet—could further drive up that risk, she added.

One of the best ways to protect yourself against Alzheimer’s is to get the shingles vaccine, which has been shown to reduce the risk of developing dementia later in life.

Martinez said it’s also crucial to lead a healthy lifestyle. Eat a balanced, healthy diet, such as the MIND and Mediterranean eating patterns, get plenty of exercise—even as little as 35 minutes a week—and stay up-to-date with your regular health check-ups.

If you test positive for HSV-1, don’t panic. Studies like this reveal an association. They aren’t claiming the virus directly causes Alzheimer’s. You can do a lot to mitigate the impact HSV-1 infections have on your brain health. “It simply highlights an opportunity to reduce the risk of Alzheimer’s through treating HSV-1 outbreaks proactively,” Idoko said.