From the Departments of Clinical Epidemiology (S.A.J.S., K.V., H.T.S., V.W.H.) and Dermatology (S.A.J.S.), Aarhus University Hospital, Denmark; Clinical Excellence Research Center (H.T.S.), Stanford University, CA; Department of Infectious Diseases (N.O.), Copenhagen University Hospital, Rigshospitalet, Denmark; and Departments of Epidemiology & Population Health (V.W.H.) and Neurology & Neurological Sciences (V.W.H.), Stanford University, CA.
Neurology. 2022 Aug 15;99(7):e660-e668. doi: 10.1212/WNL.0000000000200709.
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）是由亲神经性水痘-带状疱疹病毒（VZV）再激活引起的。带状疱疹可能通过神经炎症、脑血管病或直接神经损伤导致痴呆的发生，但目前流行病学证据有限。我们使用来自丹麦全国性的、相互关联的登记处的数据，开展了一项队列研究，在 1997 年至 2017 年间，调查带状疱疹与痴呆之间的相关性。作为次要目标，我们还研究了与颅神经（主要是眼带状疱疹）或中枢神经系统（CNS）受累相关的带状疱疹是否与痴呆的相关性更强，以及以阿尔茨海默病作为结局。
我们纳入了年龄≥40 岁、患有带状疱疹的患者和按性别和出生年份匹配的一般人群对照队列，匹配比例为 5:1。我们使用社区用药记录和医院诊断，在登记处中确定带状疱疹和痴呆病例。我们使用 Cox 回归计算了带状疱疹发生后 0-1 年和 1-21 年随访期间与痴呆相关的校正混杂因素后的危险比（HR）及其 95%置信区间（CI）。我们通过对混杂因素进行逆概率加权，比较了痴呆的累积发生率。
这项研究纳入了 247305 名带状疱疹患者和 1235890 名匹配的一般人群对照者（中位年龄 64 岁，61%为女性）。与匹配对照者相比，带状疱疹患者在第 1 年的全因痴呆 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，带状疱疹患者中有 9.7%和匹配对照者中有 10.3%被诊断为痴呆。除中枢神经系统感染患者（HR 1.94；95%CI 0.78-4.80）外，我们在亚组分析中并未观察到长期痴呆风险增加，这一结果可能并不适用于其他人群。分析以阿尔茨海默病作为单独结局时，也得到了类似的结果。
带状疱疹与痴呆风险增加无关，与预期相反，我们发现带状疱疹患者的痴呆风险略有降低。这一发现的原因尚不清楚，应该考虑到系统性错误。中枢神经系统受累患者的痴呆相对风险增加近 2 倍。由于这一罕见并发症导致的痴呆人群归因分数估计为 0.014%。因此，在老年人中普遍接种 VZV 疫苗不太可能降低痴呆风险。
