Ren Ziyang, Zhang Xuefen, Cao Lei, Wang Linlin, Li Leah, Liu Jufen
Institute of Reproductive and Child Health/National Health Commission Key Laboratory of Reproductive Health, Peking University, China; Department of Epidemiology and Biostatistics, School of Public Health, Peking University, China.
School of Public Health, Shanxi Medical University, China.
Public Health. 2025 Jul;244:105768. doi: 10.1016/j.puhe.2025.105768. Epub 2025 May 17.
Previous studies have investigated associations between childhood illness and health outcomes in early adulthood. Nevertheless, little evidence is available on the associations of childhood chronic conditions and multimorbidity with Alzheimer's disease and related dementias (ADRD) in mid-to-old age.
Multi-cohort study.
We conducted a multi-cohort study using the Survey of Health, Ageing and Retirement in Europe, English Longitudinal Study of Ageing and Health and Retirement Study. We included eight retrospectively reported childhood chronic diseases that were diagnosed by a doctor before 15/16y and defined multimorbidity as≥2 diseases. The associations with new-onset, early-onset (<65y) and late-onset (≥65y) ADRD were estimated using subdistribution hazard ratios (sHRs) and Aalen's additive hazard model (i.e., absolute risk). Results were pooled across cohorts using weighted random-effect meta-analysis.
A total of 135,588 participants aged ≥ 50y were followed up for an average of around eight years. Childhood multimorbidity was associated with higher risk of new-onset ADRD: sHR = 1.44 (95 % CI: 1.25-1.66) after adjusting for demographic and early-life factors, corresponding to excess incidence density of 223.3 per 100,000 person-years. The association was stronger with early-onset ADRD than late-onset ADRD: sHR = 2.50 (1.84-3.41) vs 1.25 (1.07-1.47), corresponding to the excess incidence density of 217.1 and 230.7 per 100,000 person-years. Of individual childhood chronic diseases, migraine, epilepsy and psychiatric disorders showed the strongest association with ADRD.
Childhood multimorbidity was associated with increased risk of ADRD in late life, highlighting the importance of preventing childhood diseases, especially neuropsychiatric conditions, to mitigate the burden of ADRD in older adults.
既往研究调查了儿童期疾病与成年早期健康结局之间的关联。然而，关于儿童期慢性病和多病共存与中老年期阿尔茨海默病及相关痴呆症（ADRD）之间的关联，现有证据较少。
多队列研究。
我们使用欧洲健康、老龄化与退休调查、英国老龄化纵向研究以及健康与退休研究进行了一项多队列研究。我们纳入了8种回顾性报告的儿童慢性病，这些疾病在15/16岁之前由医生诊断，并将多病共存定义为≥2种疾病。使用亚分布风险比（sHRs）和阿伦累加风险模型（即绝对风险）估计与新发、早发型（<65岁）和晚发型（≥65岁）ADRD的关联。使用加权随机效应荟萃分析汇总各队列的结果。
共有135588名年龄≥50岁的参与者接受了平均约8年的随访。儿童期多病共存与新发ADRD的较高风险相关：在调整人口统计学和早年因素后，sHR = 1.44（95%CI：1.25 - 1.66），相当于每10万人年额外发病密度为223.3。与早发型ADRD的关联比晚发型ADRD更强：sHR = 2.50（1.84 - 3.41）对1.25（1.07 - 1.47），相当于每10万人年额外发病密度为217.1和230.7。在个体儿童慢性病中，偏头痛、癫痫和精神障碍与ADRD的关联最强。
儿童期多病共存与晚年ADRD风险增加相关，凸显了预防儿童疾病，尤其是神经精神疾病，以减轻老年人ADRD负担的重要性。
