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.

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.

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.

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.

带状疱疹 (HZ) 是由神经营养性水痘带状疱疹病毒 (VZV) 重新激活引起的。带状疱疹可能通过神经炎症、脑血管病变或直接神经损伤导致痴呆，但流行病学证据有限。我们使用来自丹麦全国相关登记处的数据，对 1997 年至 2017 年带状疱疹与痴呆症之间的关联进行了队列研究。作为次要目标，我们检查了涉及脑神经的带状疱疹（主要是眼部带状疱疹）或中枢神经系统和阿尔茨海默病的关联是否更明显。

我们纳入了年龄≥40 岁的带状疱疹患者以及按性别和出生年份按 5:1 匹配的一般人群比较队列。我们利用社区和医院诊断中的处方记录在登记处识别了带状疱疹和痴呆症。我们使用 Cox 回归计算 0-1 年和 1-21 年随访期间带状疱疹相关痴呆的混杂因素调整风险比 (HR)，置信区间为 95%。我们比较了痴呆症的累积发病率和混杂因素的逆概率加权。

该研究纳入了 247,305 名带状疱疹患者和 1,235,890 名匹配的普通人群对照者（中位年龄 64 岁；61% 为女性）。带状疱疹患者与匹配对照者相比，第一年全因痴呆的 HR 为 0.98 (95% CI 0.92–1.04)，此后为 0.93 (95% CI 0.90–0.95)。随访结束时，9.7% 的带状疱疹患者和 10.3% 的匹配对照者被诊断出痴呆。在亚组分析中，我们观察到痴呆症的长期风险没有增加，中枢神经系统感染者可能除外（HR 1.94；95% CI 0.78-4.80）。对阿尔茨海默病作为单独结果的分析显示出类似的结果。

带状疱疹与痴呆风险增加无关，与预期相反，我们发现风险略有下降。对这一发现的解释尚不清楚，应考虑系统错误。中枢神经系统受累的患者患痴呆症的相对风险几乎增加了两倍。这种罕见并发症导致的痴呆症的人群归因比例估计为 0.014%。因此，老年人普遍接种水痘带状疱疹病毒疫苗不太可能降低痴呆风险。