Shingles, Zostavax vaccination and risk of developing dementia: a nested case–control study—results from the UK Biobank cohort

Lophatananon, Artitaya; Mekli, Krisztina; Cant, R.J.; Burns, Alistair; Dobson, Curtis B.; Itzhaki, Ruth F.; Muir, Kenneth

doi:10.1136/bmjopen-2020-045871

Cited by 35 publications

(22 citation statements)

References 21 publications

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“…13 Similar selection mechanisms are likely to explain the decreased risk of dementia in people vaccinated against HZ in recent studies. [38][39][40] Some HZ-exposed patients in our study may have had herpes simplex, which has also been implicated in dementia pathogenesis. 2 However, the association was similar when we restricted analyses to people aged 60 years or older, where validity for our prescription-based algorithm is particularly high.…”

Section: Discussionmentioning

confidence: 76%

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Incident Herpes Zoster and Risk of Dementia

et al. 2022

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Background and Objectives:Herpes zoster is caused by reactivation of the neurotrophic varicella-zoster virus. Zoster may contribute to development of dementia through neuroinflammation, cerebral vasculopathy, or direct neural damage, but epidemiological evidence is limited. We used data from linked nationwide Danish registries to conduct a cohort study of the association between zoster and dementia during 1997 to 2017. As secondary aims, we examined if associations were more pronounced for zoster involving cranial nerves (mainly ophthalmic zoster) or the central nervous system and Alzheimer’s disease as an outcome.Methods:We included people aged ≥40 years with zoster and a general population comparison cohort matched 5:1 by sex and birth year. We identified zoster and dementia in the registries using prescription records in the community and hospital diagnoses. We used Cox regression to compute confounder-adjusted hazard ratios (HR) with 95% confidence intervals (CIs) for dementia associated with zoster during 0–1 year and 1–21 years of follow-up. We compared the cumulative incidence of dementia, inverse probability-weighted for confounders.Results:The study included 247,305 people with zoster and 1,235,890 matched general population comparators (median age 64 years; 61% female). The HR of all-cause dementia was 0.98 (95% CI: 0.92–1.04) during the first year and 0.93 (95% CI: 0.90–0.95) thereafter in people with zoster versus matched comparators. Dementia was diagnosed in 9.7% of zoster patients and 10.3% of matched comparators by end of follow-up. We observed no increased long-term risk of dementia in subgroup analyses, except possibly in people with central nervous system infection (HR 1.94; 95% CI: 0.78–4.80). Analyses of Alzheimer’s disease as a separate outcome showed similar results.Discussion:Herpes zoster is not associated with increased risk of dementia, and contrary to expectation we found a small decrease in risk. The explanation for this finding is unclear, and systematic errors should be considered. Patients with central nervous system involvement had almost two-fold increased relative risk of dementia. The population attributable fraction of dementia due to this rare complication is estimated at 0.014%. Therefore, universal vaccination against varicella-zoster virus in the elderly is unlikely to reduce dementia risk.

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Section: Discussionmentioning

confidence: 76%

“…13 Similar selection mechanisms are likely to explain the decreased risk of dementia in people vaccinated against HZ in recent studies. 38-40…”

Section: Discussionmentioning

confidence: 99%

Incident Herpes Zoster and Risk of Dementia

et al. 2022

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“…The rate of influenza vaccination among adults is likely correlated with the rates of other vaccinations. Because studies have found an association between these other adult vaccinations and dementia of any cause [6,[11][12][13][14][15][16][17], it is possible that the current study's findings regarding influenza vaccination and AD risk are at least partially confounded by one of the other adulthood vaccination(s). However, the other adulthood vaccines are not as frequently indicated as the influenza vaccine, and hence it seems unlikely that they contributed significantly here.…”

Section: Strengths and Limitationsmentioning

confidence: 95%

“…Another mechanism related to innate immunity that potentially underlies the association between flu vaccination and AD is alteration of the sustained low-grade systemic elevation of proinflammatory cytokines referred to as "inflammaging" that is commonly observed among older adults [51]. Regardless of the exact mechanism, the relevance of innate immune training is supported by the growing literature that other adulthood vaccines (including those for tetanus and diphtheria, zoster, and tuberculosis) are associated with reduced dementia risk [6,[11][12][13][14][15][16][17][18][19][20][21]. Of particular interest are studies from the US and Israel that found a lower risk of AD in patients with bladder cancer who had received intravesical immunotherapy with BCG, a vaccine for tuberculosis, compared to those who had not undergone BCG immunotherapy [14,15].…”

Section: Hypothesized Mechanism(s)mentioning

confidence: 99%

“…Prevention or attenuation of microbe-related inflammation may therefore represent a rational strategy to delay or reduce the risk of neurodegenerative disease. Consistent with this hypothesis, studies have found a decreased risk of dementia associated with prior exposure to various adulthood vaccinations, including those for tetanus, diphtheria, pertussis (Tdap) [11][12][13]; poliomyelitis [11]; tuberculosis [14,15]; herpes zoster (i.e., shingles) [6,13,16,17]; and influenza [11,[18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

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Risk of Alzheimer’s Disease Following Influenza Vaccination: A Claims-Based Cohort Study Using Propensity Score Matching

Bukhbinder

Ling

Hasan³

et al. 2022

JAD

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Background: Prior studies have found a reduced risk of dementia of any etiology following influenza vaccination in selected populations, including Veterans and patients with serious chronic health conditions. However, the effect of influenza vaccination on Alzheimer’s disease (AD) risk in a general cohort of older US adults has not been characterized. Objective: To compare the risk of incident AD between patients with and without prior influenza vaccination in a large US claims database. Methods: Deidentified claims data spanning September 1, 2009 through August 31, 2019 were used. Eligible patients were free of dementia during the 6-year look-back period and≥65 years old by the start of follow-up. Propensity-score matching (PSM) was used to create flu-vaccinated and flu-unvaccinated cohorts with similar baseline demographics, medication usage, and comorbidities. Relative risk (RR) and absolute risk reduction (ARR) were estimated to assess the effect of influenza vaccination on AD risk during the 4-year follow-up. Results: From the unmatched sample of eligible patients (n = 2,356,479), PSM produced a sample of 935,887 flu–vaccinated-unvaccinated matched pairs. The matched sample was 73.7 (SD, 8.7) years of age and 56.9% female, with median follow-up of 46 (IQR, 29–48) months; 5.1% (n = 47,889) of the flu-vaccinated patients and 8.5% (n = 79,630) of the flu-unvaccinated patients developed AD during follow-up. The RR was 0.60 (95% CI, 0.59–0.61) and ARR was 0.034 (95% CI, 0.033–0.035), corresponding to a number needed to treat of 29.4. Conclusion: This study demonstrates that influenza vaccination is associated with reduced AD risk in a nationwide sample of US adults aged 65 and older.

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Effect of varicella‐zoster virus infection and antiviral treatment on the risk for dementia: A meta‐analysis of observational studies

Zhu,

Hu,

Mei

et al. 2024

Brain and Behavior

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Background and purpose:There is increasing evidence to support a role for human herpes viruses in the development of neurodegenerative disorders; however, the association between varicella‐zoster virus (VZV) infection and dementia, and the effect of antiviral therapy on the risk for dementia remain unclear.MethodsWe searched PubMed, Embase, and the Cochrane Library databases from their dates of inception to May 2023. Odds ratios (ORs) with 95% confidence intervals (CIs) served as indicators of effect sizes in evaluations of the effect of VZV infection and antiviral treatment on dementia risk. Subgroup analyses based on study design, study location, diagnostic criteria of dementia, and VZV subtype classification were also performed.ResultsA total of 10 studies with 316,846 dementia cases were included in the meta‐analysis. We found that any VZV infection (OR: 1.04, 95% CI: .97–1.12; p = .22), herpes zoster (HZ) (OR: 1.05, 95% CI: .96–1.13; p = .28), or HZ involving the cranial nerves (OR: 1.36, 95% CI: .76–2.43; p = .304) was not associated with an increased risk of dementia. The results of subgroup analyses were consistent with these findings. However, patients infected with VZV who received antiviral treatment had a lower OR than untreated patients infected with VZV. Compared to individuals not infected with VZV, antiviral therapy in those infected with VZV was associated with reduced risk for dementia.ConclusionThe association between VZV infection and dementia may be masked by antiviral treatment. Further studies with longer follow‐up times that consider the severity of VZV infection and antiviral treatment are needed to clarify the contribution of VZV infection to the risk for dementia.

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Shingles, Zostavax vaccination and risk of developing dementia: a nested case–control study—results from the UK Biobank cohort

Cited by 35 publications

References 21 publications

Incident Herpes Zoster and Risk of Dementia

Incident Herpes Zoster and Risk of Dementia

Risk of Alzheimer’s Disease Following Influenza Vaccination: A Claims-Based Cohort Study Using Propensity Score Matching

Effect of varicella‐zoster virus infection and antiviral treatment on the risk for dementia: A meta‐analysis of observational studies

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