APOE ε4 carrier status increases the long-term cognitive decline risk associated with herpes zoster

A recent study published in Research and therapy for Alzheimer’s examined the subjective risk of long-term cognitive decline associated with herpes zoster infections. It was examined whether the association varied based on apolipoprotein E e4 (APOE ε4) gene carrier status, immunocompromised conditions and vaccination against herpes zoster.

Study: Herpes zoster and long-term risk of subjective cognitive decline. Image credits: chemical industry/Shutterstock.com

Background

Age-related cognitive decline is becoming a substantial global health burden in this rapidly aging global population, and the efficient management of cognitive decline requires a thorough understanding of its risk factors. Studies show that herpes virus infections can affect the risk of cognitive decline and contribute to dementia.

Herpes zoster, commonly called shingles, occurs when the neurotrophic varicella-zoster virus, which causes chickenpox, is reactivated.

Varicella-zoster virus contains double stranded deoxyribonucleic acid (DNA) as genetic material and remains in a latent stage in the ganglion neurons after initial infection in more than 95% of infected individuals. The reactivation of the virus in the ganglia and its spread to dermatomes causes herpes zoster.

The neuroinflammation, neuronal damage, and cerebral vasculopathy that occur with herpes zoster are thought to increase the risk of dementia. Some studies have also linked herpes zoster to an increased risk of Alzheimer’s disease.

At the same time, infections with the herpes simplex virus have also been linked to decline in episodic memory and a higher risk of Alzheimer’s disease.

About the study

In the current study, the researchers examined the longitudinal association between herpes zoster and the risk of subjective cognitive decline using three well-characterized, large cohorts of male and female participants.

They also examined whether this association was modified by APOE ε4 status, immunocompromised conditions, or herpes zoster vaccination status.

The three cohorts were from the Nurses’ Health Studies I and II, and the Health Professionals Follow-Up Study. The determination of herpes zoster infections was based on data collected over several years between 2000 and 2017. Self-reported herpes zoster infections were validated using medical records.

For each of the three cohorts, subjective cognitive decline assessments were conducted over several years using six questions with a yes or no answer. These questions determined whether the participants had difficulty remembering lists, directions, storylines of television series, recent events, etc. The assessment also looked at any recent changes in memory capacity.

Data on several covariates were collected at baseline and during follow-ups. These include demographic factors such as age, gender and race and lifestyle factors such as alcohol consumption, smoking, physical activity levels and diet quality.

Other covariates include information on family history of dementia, body mass index, hypertension, diabetes, coronary heart disease, cholesterol levels, depression and a wide range of diseases such as cancer, Crohn’s disease, rheumatoid arthritis, systemic lupus erythematosus, chronic obstructive diseases. lung disease, asthma and ulcerative colitis requiring the use of immunosuppressants or steroids.

Some covariate data were specific to each gender. Menopausal status and menopausal hormone therapy are taken into account for women only, along with the husband’s education level and annual income. For male participants, the analysis was further adjusted for occupations related to the medical field.

Results

The findings confirmed that herpes zoster infection was associated with an increase in the long-term risk of subjective cognitive decline.

Furthermore, this association differed depending on whether the individual was the carrier APOE ε4 risk factor for Alzheimer’s disease.

Herpes zoster was associated with a 20% increase in the long-term risk of subjective cognitive decline. Among men, APOE ε4 carriers had a significantly higher risk of cognitive decline than men who were not carriers of the Alzheimer’s disease risk factor, but the same pattern was not observed in women.

Immunocompromised status did not appear to influence the association between herpes zoster and cognitive decline, but it was hypothesized that lack of vaccination against herpes zoster would significantly increase the risk of cognitive decline.

Some of the possible mechanisms by which herpes zoster contributes to cognitive decline were discussed in the study.

Neuroinflammation due to the virus is believed to cause neuronal damage, resulting in cognitive decline. Other possible mechanisms include cerebrovascular pathologies such as vasculopathy and the activation of herpes simplex virus-1.

Vasculopathy can result in remodeling of the vasculature, increasing the risk of ischemia and vascular occlusion. Varicella-zoster virus is also thought to increase amyloid burden and accelerate the progression of Alzheimer’s disease.

Conclusions

The results showed that herpes zoster increased the risk of subjective cognitive decline. The association between herpes zoster and cognitive decline was adjusted based on APOE ε4 carrier status, but not based on immunocompromised status. Vaccination against herpes zoster has been shown to reduce the risk of cognitive decline.