'Link Between Viral Infection and Alzheimer's Emerges in New Data'

 

• People diagnosed with HSV-1 infection had a higher risk of a subsequent Alzheimer's diagnosis.
• Antiherpetic drugs reduced Alzheimer's risk in those diagnosed with HSV-1.
• The findings apply only to people with clinical episodes of cold sores.

People diagnosed with herpes simplex virus type 1 (HSV-1), the virus responsible for cold sores, were more likely to have a subsequent Alzheimer's disease diagnosis, an analysis of U.S. commercial insurance claims suggested.

Across 344,628 Alzheimer's case-control pairs, a history of HSV-1 diagnosis was present in 1,507 people (0.44%) with Alzheimer's disease and 823 matched controls (0.24%), reported Yunhao Liu, PhD, of Gilead Sciences, a pharmaceutical company based in Foster City, California, and colleagues.

This translated to an adjusted odds ratio of 1.80 (95% CI 1.65-1.96), Liu and co-authors wrote in BMJ Openopens in a new tab or window.

Of patients diagnosed with HSV-1, those who used antiherpetic drugs were less likely to develop Alzheimer's compared with those who didn't use antiherpetics (adjusted HR 0.83, 95% CI 0.74-0.92).

"These findings place an even greater emphasis on viewing the prevention of herpesviruses as a public health priority," Liu and colleagues said.

The results confirm previous findings that people with a history of cold sores may have a higher risk of developing Alzheimer's disease, and that this risk may be reduced in people who receive antiviral treatment, noted Alberto Ascherio, MD, DrPH, of the Harvard T.H. Chan School of Public Health in Boston, who wasn't involved with the research.

"This is an observational study based on electronic data of varying quality, so the conclusions cannot be considered definitive," he wrote in a post on the Spanish Science Media Centeropens in a new tab or window website.

"For example, the vast majority of cold sore episodes are not reported in medical records, so the study's conclusions apply to a highly selected subgroup of individuals with clinical episodes of cold sores, perhaps due to clinical severity or the presence of other factors," Ascherio pointed out.

"For this reason, it would be premature for people with cold sores to worry about having an increased risk of Alzheimer's disease," he added. "However, there is growing evidence that viral infections may affect the risk of Alzheimer's disease, and it is important to initiate more definitive research."

At least 22 viruses have been tiedopens in a new tab or window to Alzheimer's, dementia, or other neurodegenerative diseases, and some researchers have proposed that latent viral infectionopens in a new tab or window may provoke Alzheimer's disease. Recent analyses also have linked receiving the herpes zoster (shingles) vaccine with reduced dementia risk in Walesopens in a new tab or window and in Australiaopens in a new tab or window.

Liu and co-authors evaluated diagnostic codes for U.S. patients with records in the IQVIA commercial claims database from 2006 to 2021. They matched patients with an Alzheimer's diagnosis in health records and those without a history of neurologic disease on age, sex, geographical region, database entry year, and number of healthcare visits.

Mean age of the sample was 73 and 65% were women. People with Alzheimer's disease had more comorbidities and a shorter follow-up time compared with controls.

The researchers also identified links between people diagnosed with HSV-2 or varicella zoster virus (chickenpox) and Alzheimer's, but not those diagnosed with cytomegalovirus.

"The molecular mechanisms underlying the role of HSV-1 and other neurotropic viruses in dementia are still not well understood," they observed. Inflammatory alterations in the brain may be important to developing Alzheimer's disease, they noted.

This study captured only a small fraction of the total population with HSV-1 infection, Liu and co-authors pointed out. "Globally, an estimated two-thirds of the population under 50 are infected with HSV-1," they wrote.

The study had other limitations, the researchers acknowledged. People ages 65 and older often are covered by Medicare and are underrepresented in commercial claims data. Due to limited data history, HSV-1 infections prior to the patient's database entry were not included, and some overlap may exist between HSV-1 and HSV-2 diagnoses.

Disclosures

This work was funded by Gilead Sciences.

Liu and most co-authors were employed by and held shares in Gilead. One co-author reported relationships with other pharmaceutical companies.

Primary Source

BMJ Open

Source Reference: opens in a new tab or windowLiu Y, et al "Association between herpes simplex virus type 1 and the risk of Alzheimer's disease: a retrospective case–control study" BMJ Open 2025; DOI: 10.1136/bmjopen-2024-093946.

https://www.medpagetoday.com/neurology/alzheimersdisease/115710