Link Between Viral Infection(HSV-1/cold sores) and Alzheimer’s Emerges in New Data

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.