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Incident Herpes Zoster and Risk of Dementia: A Population-Based Danish Cohort Study

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Background and Objectives Herpes zoster (HZ) is caused by reactivation of the neurotrophic varicella-zoster virus (VZV). Zoster may contribute to development of dementia through neuroinflammation, cerebral vasculopathy, or direct neural damage, but epidemiologic evidence is limited. We used data from linked nationwide Danish registries to conduct a cohort study of the association between zoster and dementia during 1997-2017. As secondary aims, we examined whether associations were more pronounced for zoster involving cranial nerves (mainly ophthalmic zoster) or the CNS and Alzheimer 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 (HRs) with 95% 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 vs matched comparators. Dementia was diagnosed in 9.7% of patients with zoster and 10.3% of matched comparators by the end of follow-up. We observed no increased long-term risk of dementia in subgroup analyses, except possibly in people with CNS infection (HR 1.94; 95% CI 0.78-4.80). Analyses of Alzheimer disease as a separate outcome showed similar results. Discussion HZ is not associated with an increased risk of dementia, and contrary to expectation, we found a small decrease in the risk. The explanation for this finding is unclear, and systematic errors should be considered. Patients with CNS involvement had an almost 2-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 VZV in the elderly is unlikely to reduce dementia risk.

OriginalsprogEngelsk
TidsskriftNeurology
Vol/bind99
Nummer7
Sider (fra-til)E660-E668
ISSN0028-3878
DOI
StatusUdgivet - aug. 2022

Bibliografisk note

Funding Information:
S.A.J.S. reports grants from the Edel and Wilhelm Daubenmerkls Charitable Foundation during the conduct of the study. The Department of Clinical Epidemiology, Aarhus University Hospital, receives funding for other studies from companies in the form of research grants to (and administered by) Aarhus University. None of these studies has relation to the present study. VWH was supported by NIH grant P30 AG066515.

Funding Information:
This work was supported by the Edel and Wilhelm Daubenmerkls Charitable Foundation (record number 100060 to S.A.J.S).

Publisher Copyright:
© American Academy of Neurology.

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