Shingles Tied to Long-Term Cognitive Changes

Herpes zoster (shingles) was tied to an elevated risk of subjective cognitive decline, an analysis of 150,000 U.S. healthcare professionals showed.

“In three large independent cohorts, herpes zoster was associated with an approximately 20% higher long-term risk of subjective cognitive decline,” Tian-Shin Yeh, MD, MMSc, PhD, of Taipei Medical University in Taiwan and the Harvard T.H. Chan School of Public Health in Boston, and co-authors wrote in Alzheimer’s Research and Therapy.

The risk of subjective cognitive decline was higher for APOE4 carriers versus non-carriers among men (P for interaction=0.02) but not women, the researchers reported. The association between herpes zoster and risk of subjective cognitive decline did not differ among people with or without potentially immunocompromising conditions.

“Our findings show long-term implications of shingles and highlight the importance of public health efforts to prevent and promote uptake of the shingles vaccine,” co-author Sharon Curhan, MD, of Brigham and Women’s Hospital in Boston, said in a statement.

Recent studies have suggested that dementia risk is lower in people who had a shingles vaccine. Among U.S. older adults, the recombinant shingles vaccine (Shingrix) was associated with a larger reduction in dementia risk than the live shingles vaccine (Zostavax).

Earlier studies also have linked viral illnesses with subsequent dementia. Human herpesvirus 6A and human herpesvirus 7 have been found in postmortem tissue of people with Alzheimer’s disease at levels up to twice as high as non-Alzheimer’s disease samples, for example.

Researchers have suggested that herpes simplex virus 1 (HSV-1), coupled with an APOE4 gene, may raise Alzheimer’s risk. Based on early HSV-1 research, a phase II trial of the antiviral drug valacyclovir (Valtrex) in Alzheimer’s disease is underway.

Yeh and co-authors examined data from three long-running studies of 149,327 healthcare professionals: the Nurses’ Health Study (NHS), the Nurses’ Health Study II (NHS II), and the Health Professionals Follow-Up Study (HPFS).

Mean baseline age in the NHS cohort was 64.6 years; in NHS II, it was 47.2, and in HPFS, it was 68.5. All NHS and NHS II participants were women, and all HPFS participants were men.

Participants completed health surveys every 2 years, including questions about shingles episodes and cognitive decline. Subjective cognitive decline scores were based on answers to six yes/no questions in the HPFS and seven yes/no questions in the NHS and NHS II.

The researchers calculated relative risks (RRs) for a 3-unit increment in subjective cognitive decline scores, adjusting findings for multiple variables, including age, race, health, and lifestyle.

Overall, people with a history of herpes zoster had a higher adjusted risk of subjective cognitive decline, but the duration of time since infection, when the elevated risk of subjective cognitive decline was statistically significant, differed among cohorts:

• In the NHS, the adjusted RR of a 3-unit increment in subjective cognitive decline score among people with herpes zoster was 1.14 (95% CI 1.01-1.32) for 13 or more years since infection.
• In the NHS II, herpes zoster was associated with higher risk of subjective cognitive decline in both the short term (RR 1.34, 95% CI 1.18-1.53 for 1 to 4 years) and long term (RR 1.20, 95% CI 1.08-1.34 for 13 years or more).
• In the HPFS, an elevated risk of subjective cognitive decline emerged at 5 to 8 years (RR 1.38, 95% CI 1.04-1.84) and 9 to 12 years (RR 1.42, 95% CI 1.04-1.92) after infection.

Only one cohort, the NHS II, examined subjective cognitive decline among people who were not vaccinated against herpes zoster. These results were not significant (P for interaction=0.09).

Potential limitations of the analysis included self-reporting of herpes zoster and cognitive function. Unmeasured variables also may have influenced results.

“Our study was limited to predominantly white healthcare professionals with generally high socioeconomic status and education, which could limit generalizability,” Yeh and colleagues acknowledged. “Although this uniformity may also reduce variability and enhance internal validity of health-related information, further studies among other populations are warranted.”

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