Herpes zoster and long-term risk of subjective cognitive decline

Abstract

Background: Herpes zoster (HZ), commonly known as "shingles," may contribute to cognitive decline through mechanisms such as neuroinflammation or direct neuronal injury. However, evidence on the longitudinal association between HZ and cognitive decline is conflicting and whether the risk differs by APOE ε4-carrier status has not been studied; prospective cohort studies on the association between HZ vaccination and cognitive decline are also lacking.

Methods: We included 149,327 participants from three large cohorts-the Nurses' Health Study (NHS), NHSII, and Health Professionals Follow-Up Study (HPFS)-to prospectively examine the association between HZ and subsequent subjective cognitive decline (SCD). Poisson regression was used to estimate the multivariable-adjusted relative risk (MVRR) of a 3-unit increment in SCD score according to years since HZ compared with participants with no history of HZ.

Results: Compared with individuals with no history of HZ, the MVRR (95% CI) of a 3-unit increment in SCD score was significantly and independently higher among individuals with a history of HZ, but the duration of time since HZ when the elevated risk of SCD was statistically significant differed among the cohorts. In NHS, HZ was associated with higher long-term risk of SCD; compared with individuals with no history of HZ, the MVRR (95% CI) of a 3-unit increment in SCD score was 1.14 (1.01, 1.32) for ≥ 13 years since HZ. In NHS II, HZ was associated with higher risk of SCD in both the short-term [MVRR 1.34 (1.18, 1.53) for 1-4 years] and long-term [MVRR 1.20 (1.08, 1.34) for ≥ 13 years since HZ]. In HPFS, an elevated risk of SCD was suggested across all time points. Among the subset of participants with information on APOE ε4, there was a suggestion that the association differed by APOE ε4 carrier status, but the results were not consistent between women and men. Among the subset of women with information on HZ vaccination, there was a suggestion that the long-term risk of SCD may be greater among women who were not vaccinated against HZ.

Conclusions: Data from three large independent cohorts of women and men showed that HZ was associated with higher long-term risk of SCD, and the risk may differ by APOE ε4-carrier status.

Keywords: APOE ε4; Herpes zoster; Immunocompromise; Prospective cohort study; Shingles; Subjective cognitive decline; Vaccination.

Fig. 1

Herpes Zoster and Multivariable-Adjusted Relative Risk of 3 Unit Increment in Subjective Cognitive Decline in the Nurses’ Health Study (NHS), the Nurses’ Health Study II (NHS II), and the Health Professionals Follow-Up Study (HPFS). NHS, NHS II: Multivariable models adjusted for adjusted for age, race, family history of dementia, census tract income, husband’s education, smoking history, alcohol consumption, body mass index, physical activity, diabetes mellitus, hypertension, elevated cholesterol, diet quality (AHEI-2010 Score), menopausal status, depression, post-menopausal hormonal therapy use, herpes zoster vaccination (NHS II, only), and potentially immunocompromising conditions or treatments [a report of one or more of the following: cancer (other than non-melanoma skin cancer), rheumatoid arthritis, Crohn’s disease/ulcerative colitis (inflammatory bowel disease), systemic lupus erythematosus, asthma, chronic obstructive pulmonary disease, oral steroids/corticosteroid use), stroke, and coronary heart disease]. HPFS: Multivariable model adjusted for age, race, family history of dementia, smoking history, alcohol consumption, body mass index, physical activity, diabetes mellitus, hypertension, elevated cholesterol, diet quality (AHEI-2010 Score), depression, profession, and potentially immunocompromising conditions or treatments [a report of one or more of the following: cancer (other than non-melanoma skin cancer), rheumatoid arthritis, Crohn’s disease/ulcerative colitis (inflammatory bowel disease), systemic lupus erythematosus, asthma, chronic obstructive pulmonary disease, oral steroids/corticosteroid use), stroke, and coronary heart disease