Pascalalal美国斯坦福大学 Geldsetzer团队取得了新的突破。他们开发了一个自然实验，带状疱疹疫苗对痴呆症的影响。该研究结果发表在2025年4月2日出版的国际学术期刊《自然》上。

在这里，研究小组的目的是确定减毒带状疱疹疫苗接种对痴呆症诊断的影响。为了提供与有效证据相反的因果证据，小组使用了威尔士带状疱疹疫苗的资格是根据个人准确出生年份确定的。1933年9月2日前出生的人不合格，终身不合格，但1933年9月2日或以后出生的人至少有资格在一年内接种疫苗。利用大规模电子健康记录数据，研究人员首先解释说，接种疫苗的成年人比例从只有一周大到0不一致。

1933年9月2日前一周出生的人和1933年9月2日前一周出生的人在系统上没有太大差别，除了在接种带状疱疹疫苗的概率上存在很大差异。这些对照组用于回归不连续设计，研究小组发现随访期间接受带状疱疹疫苗减少了7年，减少了3.5。％(95%置信区间(CI) = 0.6-7.1, P = 相对减少20.019) （95% CI = 6.5-33.4）。在女性中，这种缓冲比在男性中更强。该团队在不同人群(英格兰和威尔士的联合人口)中成功证实了他们的发现，使用不同类型的数据(死亡证)和主题结果(以痴呆症为主要死因的死亡)与痴呆症密切相关，但很少依赖医疗健康系统及时诊断痴呆症。通过独特的自然实验主题，本研究提供了带状疱疹疫苗预防或延缓痴呆症效果的证据。与现有相关证据相比，这种证据不太可能受到混淆和偏见的影响。

据报道，嗜神经疱疹病毒的主题可能与痴呆症的发展有关。另外，疫苗可能具有重要的脱靶免疫作用。

附：英文原文

Title: A natural experiment on the effect of herpes zoster vaccination on dementia

Author: Eyting, Markus, Xie, Min, Michalik, Felix, He, Simon, Chung, Seunghun, Geldsetzer, Pascal

Issue&Volume: 2025-04-02

Abstract: Neurotropic herpesviruses may be implicated in the development of dementia1,2,3,4,5. Moreover, vaccines may have important off-target immunological effects6,7,8,9. Here we aim to determine the effect of live-attenuated herpes zoster vaccination on the occurrence of dementia diagnoses. To provide causal as opposed to correlational evidence, we take advantage of the fact that, in Wales, eligibility for the zoster vaccine was determined on the basis of an individual’s exact date of birth. Those born before 2 September 1933 were ineligible and remained ineligible for life, whereas those born on or after 2 September 1933 were eligible for at least 1 year to receive the vaccine. Using large-scale electronic health record data, we first show that the percentage of adults who received the vaccine increased from 0.01% among patients who were merely 1 week too old to be eligible, to 47.2% among those who were just 1week younger. Apart from this large difference in the probability of ever receiving the zoster vaccine, individuals born just 1 week before 2 September 1933 are unlikely to differ systematically from those born 1week later. Using these comparison groups in a regression discontinuity design, we show that receiving the zoster vaccine reduced the probability of a new dementia diagnosis over a follow-up period of 7years by 3.5 percentage points (95% confidence interval (CI)=0.6–7.1, P=0.019), corresponding to a 20.0% (95% CI=6.5–33.4) relative reduction. This protective effect was stronger among women than men. We successfully confirm our findings in a different population (England and Wales’s combined population), with a different type of data (death certificates) and using an outcome (deaths with dementia as primary cause) that is closely related to dementia, but less reliant on a timely diagnosis of dementia by the healthcare system10. Through the use of a unique natural experiment, this study provides evidence of a dementia-preventing or dementia-delaying effect from zoster vaccination that is less vulnerable to confounding and bias than the existing associational evidence.