Association between age at onset of multimorbidity and incidence of dementia: 30 year follow-up in Whitehall II prospective cohort study
作者：Céline Ben Hassen, Aurore Fayosse, Benjamin Landré, Martina Raggi, Mikaela Bloomberg, Séverine Sabia, Archana Singh-Manoux
期刊：The BMJ
发表时间：2022/02/02
Objective: To examine the association of midlife and late life multimorbidity, includng severity of multimorbidity, with incident dementia.
Design: Prospective cohort study.
Setting: Civil service departments in London (Whitehall II study, study inception in 1985-88).
Participants: 10 095 participants, aged 35 to 55 at baseline.
Main outcome measure: Incident dementia at follow-up between 1985 and 2019. Cause specific Cox proportional hazards regression was used to examine the association of multimorbidity overall and at age 55, 60, 65, and 70 with subsequent dementia, taking into account the competing risk of death.
Results: The prevalence of multimorbidity (≥2 chronic diseases) was 6.6% (655/9937) at age 55 and 31.7% (2464/7783) at age 70; 639 cases of incident dementia occurred over a median follow-up of 31.7 years. After adjustment for sociodemographic factors and health behaviours, multimorbidity at age 55 was associated with subsequent risk of dementia (difference in incidence rate per 1000 person years 1.56, 95% confidence interval 0.62 to 2.77; hazard ratio 2.44, 95% confidence interval 1.82 to 3.26). The association weakened progressively with older age at onset of multimorbidity. At age 65, onset of multimorbidity before age 55 was associated with 3.86 (1.80 to 6.52) per 1000 person years higher incidence of dementia (hazard ratio 2.46, 1.80 to 2.26) and onset between 60 and 65 was associated with 1.85 (0.64 to 3.39) per 1000 person years higher incidence (1.51, 1.16 to 1.97). Severity of multimorbidity (≥3 chronic diseases) at age 55 was associated with a 5.22 (1.14 to 11.95) per 1000 person years higher incidence of dementia (hazard ratio 4.96, 2.54 to 9.67); the same analyses at age 70 showed 4.49 (2.33 to 7.19) per 1000 person years higher incidence (1.65, 1.25 to 2.18).
Conclusion: Multimorbidity, particularly when onset is in midlife rather than late life, has a robust association with subsequent dementia. The increasingly younger age at onset of multimorbidity makes prevention of multimorbidity in people with a first chronic disease important.
65岁及以上的老年人同时患多种类型的慢性疾病是很常见的。但是越来越多的研究发现，许多慢性疾病逐渐年轻化，且在年轻时患慢性疾病可能对今后的健康管理和其他疾病的患病率有影响。
痴呆症是一种复杂的多系统疾病。有研究发现，在患有痴呆症的老年人中，同时存在几种慢性疾病是很常见的。随着科学家们对其病理生理学探讨，越来越多的人关注各种慢性疾病与老年痴呆症之间的关系。
截图来源：The BMJ
2022年2月2日，发表在《英国医学杂志》（The BMJ）的一项大型研究发现，中年患有两种或多种慢性疾病，可能与晚年患痴呆症的风险增加有关。在这项前瞻性队列研究中，研究者纳入了10095名、基线年龄为35至55岁的参与者。然后研究者统计了在随访期间，参与者发生痴呆症的概率，并使用特定分析来检查这些参与者在55岁、60岁、65岁和70岁时，发生的慢性疾病与随后发生痴呆症之间的关联。研究中纳入的常见慢性疾病包括高血压、糖尿病、冠心病、抑郁症和慢性阻塞性肺疾病（COPD）等13种。中位随访31.7年后，研究者发现：55岁时患有≥2种慢性病的概率为6.6%，70岁时患有≥2种慢性病的概率为31.7%，共有639人患痴呆症。在调整了各种混杂因素（如年龄、性别、种族、教育、饮食和生活方式等）后发现，与没有出现任何疾病的人相比，55岁时患有≥2种慢性疾病的患者与随后痴呆症的发生风险增加144%有关（HR=2.44）；两组发病率差异为1.56/1000人-年。这种关联随着出现多种慢性疾病时年龄的增长而逐渐减弱。在70岁之前，发病年龄每提前5岁，患痴呆症的风险就会增加18%。研究人员分析更严重的多发病（即同时患有更多种慢性病），进一步强调了发病年龄较小与今后痴呆症发生风险之间的关联。研究人员指出了一些局限性，如某些痴呆症患者的病例可能被错误的分类，以及参与研究的人可能比普通人群更健康。然而，研究人员表示，这是一项进行了30多年随访的大型研究，研究者使用死亡作为结果指标的进一步分析后发现结果仍相似，这也增加了研究者对该结论的信心。该研究的第一作者、伦敦大学学院（University College London）的Céline Ben Hassen教授指出：“鉴于缺乏有效治疗痴呆症的方法，寻找预防痴呆症的方法势在必行，该研究强调了在成年期间预防和管理慢性疾病，对老年痴呆症的减轻作用。”结论中指出，在中年时出现慢性疾病与随后痴呆症的发生密切相关。目前多发病出现的年龄越来越小，在已经出现第一种慢性病的患者中，预防出现多发慢性病很重要。参考资料
[1] Hassen, C. B., Fayosse, A., Landré, B., Raggi, M., Bloomberg, M., Sabia, S., & Singh-Manoux, A. (2022). Association between age at onset of multimorbidity and incidence of dementia: 30 year follow-up in Whitehall II prospective cohort study. bmj, 376.
[2] Midlife chronic conditions linked to increased dementia risk later in life. Retrieved RELEASE 2-FEB-2022, from https://www.eurekalert.org/news-releases/941953
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