Simmonds Emily, Han Jun, Kirov George, Sharp David J, Massey Thomas H, Escott-Price Valentina
UK Dementia Research Institute, Cardiff University, United Kingdom.
Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, United Kingdom.
Neurology. 2025 Aug 12;105(3):e213866. doi: 10.1212/WNL.0000000000213866. Epub 2025 Jul 3.
Traumatic brain injury (TBI) can increase vulnerability to neurodegenerative disorders. The association between TBI and dementia has been previously reported, but studies have relied on self-reporting of TBI and often do not appropriately adjust for relevant risk factors or cover enough time to include both individuals at age of highest TBI risk and age of dementia onset. This study uses electronic health records, which include over 20 years of data and 1.7 million individuals with hospital or general practitioner diagnoses of dementia and TBI. Therefore, the aim of this study was to assess the association between TBI and dementia and between TBI and dementia subtypes (Alzheimer disease [AD], vascular dementia [VaD], and unspecified dementia).
We performed a population-based study using Welsh (UK) electronic health records to estimate effect of TBI on the risk of dementia for individuals aged between 30 and 65 years in 1999 without a previous dementia diagnosis. The long-term risk of dementia after TBI was established using Cox proportional hazard models adjusting for sex, social deprivation, and other comorbidities. The effect of the time between TBI and dementia was investigated with time-stratified analyses. We assessed separately the risks of AD, VaD, and unspecified dementia related to TBI.
Our study investigated 42,974 individuals with dementia (mean diagnosis age of 70 [SD = 10.5]), 10,164 individuals with a history of TBI, and 1,737,480 controls (mean age of 62 [SD = 11.9]). 49% of all individuals were female. TBI was associated with increased risk of dementia (hazard ratio [HR] = 2.32, 95% CI [1.88-2.85], = 3.8 × 10), with the risk increasing for multiple TBIs (HR = 1.22, 95% CI [1.08-1.38], = 1.8 × 10). The effect size of association between TBI and dementia was higher in people diagnosed with VaD (HR = 1.71, 95% CI [1.06-2.75], = 0.027) and unspecified dementia (HR = 1.90, 95% CI [1.29-2.80], = 0.0011) compared with the AD group (HR = 1.44, 95% CI [0.84-2.48], = 0.189).
Our study confirms that TBI increases dementia risk. We have shown a higher risk of VaD and unspecified dementia in those with a TBI, compared with AD. This study will direct future research into which biological mechanisms drive the association between TBI and dementia.
创伤性脑损伤(TBI)会增加患神经退行性疾病的易感性。此前已有关于TBI与痴呆症之间关联的报道,但这些研究依赖于TBI的自我报告,且往往没有对相关风险因素进行适当调整,或者没有涵盖足够长的时间以纳入处于TBI风险最高年龄和痴呆症发病年龄的个体。本研究使用电子健康记录,其中包含超过20年的数据以及170万患有痴呆症和TBI且由医院或全科医生诊断的个体。因此,本研究的目的是评估TBI与痴呆症之间以及TBI与痴呆症亚型(阿尔茨海默病[AD]、血管性痴呆[VaD]和未特定的痴呆症)之间的关联。
我们利用威尔士(英国)电子健康记录进行了一项基于人群的研究,以评估TBI对1999年年龄在30至65岁且既往无痴呆症诊断个体患痴呆症风险的影响。使用Cox比例风险模型对性别、社会剥夺和其他合并症进行调整后,确定TBI后痴呆症的长期风险。通过时间分层分析研究TBI与痴呆症之间的时间间隔的影响。我们分别评估了与TBI相关的AD、VaD和未特定的痴呆症的风险。
我们的研究调查了42974名患有痴呆症的个体(平均诊断年龄为70岁[标准差=10.5])、10164名有TBI病史的个体以及1737480名对照个体(平均年龄为62岁[标准差=11.9])。所有个体中49%为女性。TBI与痴呆症风险增加相关(风险比[HR]=2.32,95%置信区间[1.88 - 2.85],P = 3.8×10⁻⁶),多次TBI的风险增加(HR = 1.22,95%置信区间[1.08 - 1.38],P = 1.8×10⁻³)。与AD组(HR = 1.44,95%置信区间[0.84 - 2.48],P = 0.189)相比,在被诊断为VaD(HR = 1.71,95%置信区间[1.06 - 2.75],P = 0.027)和未特定的痴呆症(HR = 1.90,95%置信区间[1.29 - 2.80],P = 0.0011)的个体中,TBI与痴呆症之间关联的效应大小更高。
我们的研究证实TBI会增加痴呆症风险。我们已经表明,与AD相比,有TBI的个体患VaD和未特定的痴呆症的风险更高。本研究将指导未来对驱动TBI与痴呆症之间关联的生物学机制的研究。