美国斯坦福大学Pascal Geldsetzer团队研究了带状疱疹疫苗接种与痴呆症的发生的相关性。该研究于2025年4月23日发表于国际一流学术期刊《美国医学会杂志》上。

最近来自威尔士的一项准实验的证据表明，带状疱疹（HZ）疫苗似乎可以预防或延缓痴呆症。利用澳大利亚类似的准实验，研究组调查了HZ疫苗接种对不同人群和卫生系统设置中痴呆发生的影响。

为了确定HZ疫苗接种对接受新诊断为痴呆的概率的影响。研究组在澳大利亚从2016年11月1日开始，通过初级保健临床医生向70至79岁的个人免费提供减毒HZ活疫苗。因此，那些在2016年11月1日前几周过80岁生日的人不会有资格，而那些在几周后过80岁生日的人则有资格。这个准实验的关键优势在于，人们不会期望这些年龄仅相差几分钟的对照组在任何健康特征和行为上平均存在差异。使用回归不连续设计，对澳大利亚65家全科诊所的初级卫生保健记录与出生周信息进行了分析。暴露因素为根据出生日期接种HZ疫苗的资格。主要结局为初级保健电子健康记录数据中记录的痴呆新诊断。

截至2016年11月1日，在101219名患者中，52.7%为女性，平均年龄为62.6岁（SD，9.3岁）。在HZ疫苗接种资格阈值（1936年11月2日）之前出生的人与之后出生的人在过去的预防性卫生服务和过去的慢性病诊断方面保持了良好的平衡。出生前不久与出生后不久出生的患者接种HZ疫苗的概率突然增加了16.4个百分点（95%CI，13.2-19.5；P<0.001）。因此，HZ疫苗接种计划的资格规则创建了出生在出生日期资格阈值两侧的比较组，除了接受感兴趣的干预（HZ疫苗接种）的概率存在很大差异外，这些比较组可能彼此相似。这项研究发现，接种HZ疫苗的资格（即1936年11月2日前不久与后不久出生）使7.4年内接受新的痴呆症诊断的概率降低了1.8个百分点（95%CI，0.4-3.3个百分点；P = .01）。有资格接种HZ疫苗并不影响接受其他预防性卫生服务（包括其他疫苗）的概率，也不影响接受痴呆症以外常见慢性病诊断的概率。

综上，通过利用准实验和威尔士在不同人群中的确证结果，这项研究提供了HZ疫苗对痴呆症的潜在益处的证据，这比更常见的关联研究更有可能是因果关系。

附：英文原文

Title: Herpes Zoster Vaccination and Dementia Occurrence

Author: Michael Pomirchy, Christian Bommer, Fabienne Pradella, Felix Michalik, Ruth Peters, Pascal Geldsetzer

Issue&Volume: 2025-04-23

Abstract:

Importance  Recent evidence from a quasi-experiment in Wales showed that herpes zoster (HZ) vaccination appears to prevent or delay dementia. Exploiting a similar quasi-experiment in Australia, this study investigated the effect of HZ vaccination on dementia occurrence in a different population and health system setting.

Objective  To determine the effect of HZ vaccination on the probability of receiving a new diagnosis of dementia.

Design, Setting, and Participants  In Australia, starting November 1, 2016, live attenuated HZ vaccination was provided free to individuals aged 70 to 79 years through primary care clinicians. Thus, individuals whose 80th birthday was just a few weeks before November 1, 2016, never became eligible, whereas those whose 80th birthday was just a few weeks later were eligible. The key strength of this quasi-experiment is that one would not expect that these comparison groups who differ in age only minutely would, on average, differ in any health characteristics and behaviors. Primary health care records were analyzed with week-of-birth information from 65 general practices across Australia, using a regression discontinuity design.

Exposure  Eligibility for HZ vaccination based on date of birth.

Main Outcome  New diagnoses of dementia as recorded in primary care electronic health record data.

Results  In this sample of 101219 patients, 52.7% were women and mean age was 62.6 years (SD, 9.3 years) as of November 1, 2016. Individuals born just before vs just after the date-of-birth eligibility threshold (November 2, 1936) for HZ vaccination were well balanced in their past preventive health services uptake and past chronic disease diagnoses. There was an abrupt increase of 16.4 percentage points (95% CI, 13.2-19.5; P<.001) in the probability of ever receiving HZ vaccination between patients born shortly before vs shortly after the date-of-birth eligibility threshold. The eligibility rules of the HZ vaccination program thus created comparison groups born just on either side of the date-of-birth eligibility threshold who were likely similar to each other, except for a large difference in their probability of receiving the intervention (HZ vaccination) of interest. This study found that eligibility for HZ vaccination (ie, being born shortly after vs shortly before November 2, 1936) decreased the probability of receiving a new dementia diagnosis during 7.4 years by 1.8 percentage points (95% CI, 0.4-3.3 percentage points; P=.01). Being eligible for HZ vaccination did not affect the probability of taking up other preventive health services (including other vaccinations) or the probability of receiving a diagnosis of common chronic conditions other than dementia.

Conclusions and Relevance  By taking advantage of a quasi-experiment and corroborating findings from Wales in a different population, this study provides evidence of the potential benefits of HZ vaccination for dementia that is more likely to be causal than that of more commonly conducted associational studies.

DOI: 10.1001/jama.2025.5013

Source: https://jamanetwork.com/journals/jama/fullarticle/2833335