Raj Rahul, Kaprio Jaakko, Korja Miikka, Mikkonen Era D, Jousilahti Pekka, Siironen Jari
Department of Neurosurgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Department of Public Health, University of Helsinki, Helsinki, Finland.
PLoS Med. 2017 Jul 5;14(7):e1002316. doi: 10.1371/journal.pmed.1002316. eCollection 2017 Jul.
Previous epidemiological studies suggest that working-aged persons with a history of moderate-to-severe traumatic brain injury (TBI) may have an increased risk for developing neurodegenerative disease (NDD) while persons with a history of mild TBI do not. In this comprehensive nationwide study in Finland, we assessed the risk of NDD and history of moderate-to-severe TBI in the working-age population.
We performed a population-based follow-up study using the Finnish Care Register for Health Care to identify all persons between the ages of 18 and 65 years hospitalized during 1987-2014 due to TBI who did not have a baseline NDD diagnosis. We compared the risk of hospitalization with NDD between persons hospitalized due to moderate-to-severe TBI (intracranial lesions) and persons hospitalized due to mild TBI (no intracranial lesions). Follow-up NDD diagnoses were recorded from 1 year following the TBI to the end of 2014. NDD diagnoses included dementia, Parkinson disease, and amyotrophic lateral sclerosis. We used a Cox proportional hazards model, adjusting for age, sex, education, and socioeconomic group, to assess the association between TBI and NDD. In total, 19,936 and 20,703 persons with a history of moderate-to-severe TBI and mild TBI, respectively, were included. The overall time at risk was 453,079 person-years (median 10 years per person). In total, 3.5% (N = 696) persons in the moderate-to-severe TBI group developed NDD compared to 1.6% (N = 326) in the mild TBI group. After adjusting for covariates, moderate-to-severe TBI was associated with an increased risk for NDD, with a hazard ratio (HR) of 1.8 (95% CI 1.6-2.1) compared to mild TBI. Of the NDD subtypes, only moderate-to-severe TBI was associated with an increased risk for dementia (HR 1.9, 95% CI 1.6-2.2). Yet, this large-scale epidemiological study does not prove that there is a causal relationship between moderate-to-severe TBI and NDD. Further, the Care Register for Health Care includes only hospitalized persons; thus, patients diagnosed with NDD in the outpatient setting may have been missed. Additional limitations include the potential for miscoding and unmeasured confounds.
In working-aged persons, a history of moderate-to-severe TBI is associated with an increased risk for future dementia but not for Parkinson disease or amyotrophic lateral sclerosis.
先前的流行病学研究表明，有中度至重度创伤性脑损伤（TBI）病史的工作年龄人群患神经退行性疾病（NDD）的风险可能增加，而轻度TBI病史的人群则不然。在芬兰这项全面的全国性研究中，我们评估了工作年龄人群中NDD的风险以及中度至重度TBI的病史。
我们使用芬兰医疗保健护理登记册进行了一项基于人群的随访研究，以识别1987年至2014年期间因TBI住院但没有基线NDD诊断的所有18至65岁的人。我们比较了因中度至重度TBI（颅内病变）住院的人与因轻度TBI（无颅内病变）住院的人患NDD的住院风险。从TBI后的1年到2014年底记录随访NDD诊断。NDD诊断包括痴呆、帕金森病和肌萎缩侧索硬化症。我们使用Cox比例风险模型，对年龄、性别、教育程度和社会经济群体进行调整，以评估TBI与NDD之间的关联。总共纳入了分别有中度至重度TBI病史和轻度TBI病史的19936人和20703人。总的风险时间为453079人年（每人中位数10年）。中度至重度TBI组中3.5%（N = 696）的人患NDD，而轻度TBI组中为1.6%（N = 326）。在对协变量进行调整后，中度至重度TBI与NDD风险增加相关，与轻度TBI相比，风险比（HR）为1.8（95%CI 1.6 - 2.1）。在NDD亚型中，只有中度至重度TBI与痴呆风险增加相关（HR 1.9，95%CI 1.6 - 2.2）。然而，这项大规模的流行病学研究并未证明中度至重度TBI与NDD之间存在因果关系。此外，医疗保健护理登记册仅包括住院患者；因此，可能遗漏了在门诊环境中被诊断为NDD的患者。其他局限性包括可能存在编码错误和未测量的混杂因素。
在工作年龄人群中，中度至重度TBI病史与未来患痴呆的风险增加相关，但与帕金森病或肌萎缩侧索硬化症无关。
