Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis.
Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
JAMA Netw Open. 2023 Jan 3;6(1):e2250126. doi: 10.1001/jamanetworkopen.2022.50126.
Factors associated with the risk of dementia remain to be fully understood. Systemic infections are hypothesized to be such factors and may be targets for prevention and screening.
To investigate the association between hospitalization with infection and incident dementia.
DESIGN, SETTING, AND PARTICIPANTS: Data from the community-based Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort study, were used. Enrollment occurred at 4 research centers in the US, initiated in 1987 to 1989. The present study includes data up to 2019, for 32 years of follow-up. Data analysis was performed from April 2021 to June 2022.
Hospitalizations with infections were identified via medical record review for selected International Classification of Diseases, Ninth Revision (ICD-9) and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes, from baseline until administrative censoring or dementia diagnosis. Participants were considered unexposed until first hospitalization with infection and exposed thereafter. Selected infection subtypes were also considered.
Incident dementia and time-to-event data were identified through surveillance of ICD-9 and ICD-10 hospitalization and death certificate codes, in-person assessments, and telephone interviews. A sensitivity analysis was conducted excluding cases occurring within 3 years or beyond 20 years from exposure. Data were collected before study hypothesis formulation.
Of the 15 792 ARIC study participants, an analytical cohort of 15 688 participants who were dementia free at baseline and of Black or White race were selected (8658 female [55.2%]; 4210 Black [26.8%]; mean [SD] baseline age, 54.7 [5.8] years). Hospitalization with infection occurred among 5999 participants (38.2%). Dementia was ascertained in 2975 participants (19.0%), at a median (IQR) of 25.1 (22.2-29.1) years after baseline. Dementia rates were 23.6 events per 1000 person-years (95% CI, 22.3-25.0 events per 1000 person-years) among the exposed and 5.7 events per 1000 person-years (95% CI, 5.4-6.0 events per 1000 person-years) among the unexposed. Patients hospitalized with infection were 2.02 (95% CI, 1.88-2.18; P < .001) and 1.70 (95% CI, 1.55-1.86; P < .001) times more likely to experience incident dementia according to unadjusted and fully adjusted Cox proportional hazards models compared with individuals who were unexposed. When excluding individuals who developed dementia less than 3 years or more than 20 years from baseline or the infection event, the adjusted hazard ratio was 5.77 (95% CI, 4.92-6.76; P < .001). Rates of dementia were significantly higher among those hospitalized with respiratory, urinary tract, skin, blood and circulatory system, or hospital acquired infections. Multiplicative and additive interactions were observed by age and APOE-ε genotype.
Higher rates of dementia were observed among participants who experienced hospitalization with infection. These findings support the hypothesis that infections are factors associated with higher risk of dementias.
重要性：与痴呆风险相关的因素仍有待充分了解。全身性感染被认为是此类因素，并可能成为预防和筛查的目标。
目的：调查感染性住院与痴呆发病的相关性。
设计、地点和参与者：本研究使用了社区动脉粥样硬化风险（ARIC）研究的数据，这是一项前瞻性队列研究，于 1987 年至 1989 年在美国 4 个研究中心进行了入组。本研究截至 2019 年，随访时间长达 32 年。数据分析于 2021 年 4 月至 2022 年 6 月进行。
暴露：通过对选定的国际疾病分类第 9 版（ICD-9）和国际疾病分类第 10 版修订版（ICD-10）代码的医疗记录进行回顾，确定感染性住院，基线至行政 censoring 或痴呆诊断期间均进行了评估。参与者在首次感染性住院前被认为是未暴露的，此后则被视为暴露。还考虑了选定的感染亚组。
主要结局和测量：通过 ICD-9 和 ICD-10 住院和死亡证明代码的监测、现场评估和电话访谈，确定了痴呆发病和时间事件数据。进行了一项敏感性分析，排除了基线后 3 年内或 20 年后发生的病例。数据收集在研究假设制定之前进行。
结果：在 15792 名 ARIC 研究参与者中，选择了基线时无痴呆且为黑种人或白种人的 15688 名分析队列参与者（8658 名女性[55.2%]；4210 名黑种人[26.8%]；平均[SD]基线年龄，54.7[5.8]岁）。5999 名参与者发生了感染性住院（38.2%）。在基线后中位数（IQR）25.1（22.2-29.1）年时，2975 名参与者（19.0%）确诊为痴呆。暴露组的痴呆发生率为 23.6 例/1000 人年（95%CI，22.3-25.0 例/1000 人年），未暴露组的痴呆发生率为 5.7 例/1000 人年（95%CI，5.4-6.0 例/1000 人年）。与未暴露者相比，感染性住院患者发生痴呆的可能性分别为 2.02（95%CI，1.88-2.18；P<0.001）和 1.70（95%CI，1.55-1.86；P<0.001）倍。根据未调整和完全调整的 Cox 比例风险模型，与未暴露者相比，排除了基线后 3 年内或 20 年内发生痴呆或感染事件的个体，调整后的风险比为 5.77（95%CI，4.92-6.76；P<0.001）。有呼吸道、尿路感染、皮肤、血液和循环系统或医院获得性感染住院的患者，痴呆发生率显著更高。年龄和 APOE-ε 基因型存在乘法和加法交互作用。
结论和相关性：发生感染性住院的参与者中痴呆发生率更高。这些发现支持了感染是与痴呆风险增加相关的因素的假设。
