Department of Population Medicine at Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts.
Department of Clinical Epidemiology, Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark.
JAMA Neurol. 2021 Dec 1;78(12):1461-1470. doi: 10.1001/jamaneurol.2021.3895.
Influenza has been associated with the risk of developing Parkinson disease, but the association is controversial.
To examine whether prior influenza and other infections are associated with Parkinson disease more than 10 years after infection.
DESIGN, SETTING, AND PARTICIPANTS: This case-control study used data from 1977 to 2016 from the Danish National Patient Registry. All individuals with Parkinson disease, excluding those with drug-induced parkinsonism, were included and matched to 5 population controls on sex, age, and date of Parkinson diagnosis. Data were analyzed from December 2019 to September 2021.
Infections were ascertained between 1977 and 2016 and categorized by time from infection to Parkinson disease diagnosis. To increase specificity of influenza diagnoses, influenza exposure was restricted to months of peak influenza activity.
Parkinson disease diagnoses were identified between January 1, 2000, and December 31, 2016. Crude and adjusted odds ratios (ORs) and 95% CIs were calculated by conditional logistic regression overall and stratified by time between infection and Parkinson disease (5 years or less, more than 5 to 10 years, more than 10 years).
Of 61 626 included individuals, 23 826 (38.7%) were female, and 53 202 (86.3%) were older than 60 years. A total of 10 271 individuals with Parkinson disease and 51 355 controls were identified. Influenza diagnosed at any time during a calendar year was associated with Parkinson disease more than 10 years later (OR, 1.73; 95% CI, 1.11-2.71). When influenza exposure was restricted to months of highest influenza activity, an elevated OR with a wider confidence interval was found (OR, 1.52; 95% CI, 0.80-2.89). There was no evidence of an association with any type of infection more than 10 years prior to Parkinson disease (OR, 1.04; 95% CI, 0.98-1.10). Several specific infections yielded increased odds of Parkinson disease within 5 years of infection, but results were null when exposure occurred more than 10 years prior.
In this case-control study, influenza was associated with diagnoses of Parkinson disease more than 10 years after infection. These observational data suggest a link between influenza and Parkinson disease but do not demonstrate causality. While other infections were associated with Parkinson disease diagnoses soon after infection, null associations after more than 10 years suggest these shorter-term associations are not causal.
流感与帕金森病的发病风险相关，但这种关联存在争议。
探究流感和其他感染是否在感染 10 年以上后与帕金森病发病相关。
设计、地点和参与者：这项病例对照研究使用了 1977 年至 2016 年丹麦全国患者登记处的数据。纳入了所有帕金森病患者（不包括药物引起的帕金森病），并按性别、年龄和帕金森病诊断日期与 5 名人群对照进行匹配。数据于 2019 年 12 月至 2021 年 9 月进行分析。
1977 年至 2016 年期间确定了感染情况，并按感染至帕金森病诊断的时间进行了分类。为了提高流感诊断的特异性，将流感暴露限制在流感活动高峰期的月份。
2000 年 1 月 1 日至 2016 年 12 月 31 日期间确定了帕金森病的诊断。通过条件逻辑回归，总体计算并调整了比值比（OR）和 95%置信区间（CI），并按感染与帕金森病发病时间（5 年或以内、5 至 10 年、10 年以上）进行分层。
在纳入的 61626 名患者中，23826 名（38.7%）为女性，53202 名（86.3%）年龄大于 60 岁。共发现 10271 名帕金森病患者和 51355 名对照。在任何一年的日历月中诊断出的流感与 10 年以上后的帕金森病发病相关（OR，1.73；95%CI，1.11-2.71）。当将流感暴露限制在流感活动高峰期的月份时，发现置信区间较宽的 OR 升高（OR，1.52；95%CI，0.80-2.89）。没有证据表明任何类型的感染在帕金森病发病前 10 年以上与帕金森病发病相关（OR，1.04；95%CI，0.98-1.10）。几种特定的感染在感染后 5 年内使帕金森病的发病几率增加，但当暴露发生在 10 年以上前时，结果为无效。
在这项病例对照研究中，流感与感染 10 年以上后的帕金森病诊断相关。这些观察性数据表明流感与帕金森病之间存在关联，但不能证明因果关系。虽然其他感染与感染后不久的帕金森病诊断相关，但 10 年以上的无效关联表明这些短期关联不是因果关系。
