Show 1394: Viruses, Vaccines and Alzheimer Disease

 This week, we explore the role viruses may play in the development of dementia. That certainly sounds like a downer, but here is the brighter side: vaccines can significantly lower the risk! Joe and Terry talk to two leading researchers about their findings and the implications of antivirals or vaccines and Alzheimer Disease.

Does the Herpes Virus Contribute to Dementia?

More than 40 years ago, a pathologist named Melvyn Ball published a hypothesis that herpes simplex 1, the virus that causes cold sores, might be contributing to dementia. His suggestion was disregarded for years. Recently, though, Dr. Bodil Weidung and her colleagues have analyzed epidemiological data from Sweden (Journal of Alzheimer’s Disease, Feb. 13, 2024). The study lasted 15 years and included a thousand Swedish people who were 70 years old between 2001 and 2005, when they were recruited. At that time, they gave blood.

When the scientists analyzed the blood samples for evidence of herpes infection, they discovered that herpes antibodies doubled the risk of developing dementia. Just as in the US, about 80% of older Swedes have had a cold sore. Relatively few, about 6%, had been treated with antiviral medication. The association was surprisingly strong: people who’d had herpes were twice as likely to come down with dementia. The sample was too small to detect the risk for Alzheimer disease.

Could Antiviral Treatments Help?

Dr. Weidung is eager to test the efficacy of antiviral medications such as valacyclovir. She conducted a pilot study showing that this treatment was safe and feasible for people with mild Alzheimer disease (Alzheimer’s & Dementia: Translational Research & Clinical Intervention, March 14, 2022).  We don’t know of any large randomized controlled trials that have been conducted to test the efficacy of this treatment. Hopefully, a few are already underway.

Vaccines and Alzheimer Disease:

What would you say to the idea that you could get vaccinated against dementia? So far as we know, scientists have not conducted randomized, double-blind trials on this topic. However, health authorities in Wales created conditions that closely resembled a randomized trial. When the vaccine against shingles was first introduced there, people born on or after Sept. 2, 1933, were eligible and those older than that were excluded. This established a quasi-randomized situation, because no other factors determined who could and who could not be vaccinated (Alzheimer’s & Dementia, Dec. 2023).

The consequence of this unusual scenario is that researchers could say not just that shingles vaccinations was associated with a lower risk of dementia. They were able to claim that this connection was causative: “receiving the herpes zoster vaccine reduced the probability of a new dementia diagnosis over a follow-up period of seven years by 3.5 percentage points (95% CI: 0.6 - 7.1, p=0.019), corresponding to a 19.9% relative reduction in the occurrence of dementia” (medRxiv, May 25, 2023).  That is quite substantial protection from dementia, along with the protection the vaccine offers against shingles.

Shingrix Might Be Better Than Zostavax:

New research demonstrates that the Shingrix shot also reduces the risk for dementia (Nature Medicine, July 25, 2024). These scientists utilized the rapid switch from Zostavax to Shingrix in the US. Their analysis showed that the Shingrix shot increases time to a dementia diagnosis by 17 percent. That's the equivalent of an extra 164 days without a dementia diagnosis.

Do Viruses Cause Alzheimer Disease?

The link between infection and dementia might indicate that viruses like herpes and varicella zoster cause dementia. Or perhaps the link is through the immune response to infection. Other research has shown that amyloid-beta plaque is part of the brain’s immune response to infection. We don’t know if it might react differently to these viruses than to other pathogens.

Do We Need a Paradigm Shift to Viruses, Vaccines and Alzheimer Disease?

The idea that pathogens might contribute in some way to the development of amyloid-beta plaque and consequently to Alzheimer disease has been around for decades. Nonetheless, few scientists have spent time studying this possibility. Most of the funding and research effort has gone into ways of removing the plaque. The FDA has approved three drugs that do so–aducanumab (Aduhelm, now off the market), lecanemab (Leqembi) and donanemab (Kisunla). Unfortunately, these drugs aren’t very effective at helping people regain cognitive function or maintain independent lives. What if, instead, scientists focused their attention upstream and studied antiviral medications for people with herpes or shingles vaccine to reduce the risk from varicella zoster?

This Week's Guests:

Dr. Bodil Weidung is an associated researcher in the Department of Public Health and caring Sciences and Clinical Geriatrics at Uppsala University in Sweden.

Pascal Geldsetzer, MD, is an assistant Professor of Medicine in the Division of Primary Care and Population Health at Stanford University School of Medicine in Palo Alto, California. He is also affiliated with the Department of Epidemiology and Population Health as well as the Department of Health Policy, King Center for Global Development and the Stanford Centers for Population Health Sciences, Innovation in Global Health and Artificial Intelligence in Medicine and Imaging.

[caption id="attachment_131695" align="alignnone" width="768"] Pascal Geldsetzer, MD
Courtesy Stanford Medicine[/caption]