Hayes Jasmeet P, Logue Mark W, Sadeh Naomi, Spielberg Jeffrey M, Verfaellie Mieke, Hayes Scott M, Reagan Andrew, Salat David H, Wolf Erika J, McGlinchey Regina E, Milberg William P, Stone Annjanette, Schichman Steven A, Miller Mark W
National Center for PTSD, VA Boston Healthcare System, Boston, MA, USA.
Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA.
Brain. 2017 Mar 1;140(3):813-825. doi: 10.1093/brain/aww344.
Moderate-to-severe traumatic brain injury is one of the strongest environmental risk factors for the development of neurodegenerative diseases such as late-onset Alzheimer's disease, although it is unclear whether mild traumatic brain injury, or concussion, also confers risk. This study examined mild traumatic brain injury and genetic risk as predictors of reduced cortical thickness in brain regions previously associated with early Alzheimer's disease, and their relationship with episodic memory. Participants were 160 Iraq and Afghanistan War veterans between the ages of 19 and 58, many of whom carried mild traumatic brain injury and post-traumatic stress disorder diagnoses. Whole-genome polygenic risk scores for the development of Alzheimer's disease were calculated using summary statistics from the largest Alzheimer's disease genome-wide association study to date. Results showed that mild traumatic brain injury moderated the relationship between genetic risk for Alzheimer's disease and cortical thickness, such that individuals with mild traumatic brain injury and high genetic risk showed reduced cortical thickness in Alzheimer's disease-vulnerable regions. Among males with mild traumatic brain injury, high genetic risk for Alzheimer's disease was associated with cortical thinning as a function of time since injury. A moderated mediation analysis showed that mild traumatic brain injury and high genetic risk indirectly influenced episodic memory performance through cortical thickness, suggesting that cortical thinning in Alzheimer's disease-vulnerable brain regions is a mechanism for reduced memory performance. Finally, analyses that examined the apolipoprotein E4 allele, post-traumatic stress disorder, and genetic risk for schizophrenia and depression confirmed the specificity of the Alzheimer's disease polygenic risk finding. These results provide evidence that mild traumatic brain injury is associated with greater neurodegeneration and reduced memory performance in individuals at genetic risk for Alzheimer's disease, with the caveat that the order of causal effects cannot be inferred from cross-sectional studies. These results underscore the importance of documenting head injuries even within the mild range as they may interact with genetic risk to produce negative long-term health consequences such as neurodegenerative disease.
中重度创伤性脑损伤是诸如迟发性阿尔茨海默病等神经退行性疾病发生的最强环境风险因素之一，不过尚不清楚轻度创伤性脑损伤（即脑震荡）是否也会带来风险。本研究考察了轻度创伤性脑损伤和遗传风险，将其作为先前与早期阿尔茨海默病相关的脑区皮质厚度降低的预测因素，以及它们与情景记忆的关系。研究参与者为160名年龄在19岁至58岁之间的伊拉克和阿富汗战争退伍军人，其中许多人被诊断患有轻度创伤性脑损伤和创伤后应激障碍。利用迄今为止最大规模的阿尔茨海默病全基因组关联研究的汇总统计数据，计算了阿尔茨海默病发病的全基因组多基因风险评分。结果显示，轻度创伤性脑损伤调节了阿尔茨海默病遗传风险与皮质厚度之间的关系，即患有轻度创伤性脑损伤且遗传风险高的个体在阿尔茨海默病易损区域的皮质厚度降低。在患有轻度创伤性脑损伤的男性中，阿尔茨海默病的高遗传风险与自受伤以来随时间变化的皮质变薄有关。一项调节中介分析表明，轻度创伤性脑损伤和高遗传风险通过皮质厚度间接影响情景记忆表现，这表明阿尔茨海默病易损脑区的皮质变薄是记忆表现下降的一种机制。最后，对载脂蛋白E4等位基因、创伤后应激障碍以及精神分裂症和抑郁症遗传风险的分析证实了阿尔茨海默病多基因风险发现的特异性。这些结果提供了证据，表明轻度创伤性脑损伤与阿尔茨海默病遗传风险个体中更大程度的神经退行性变和记忆表现下降有关，但需注意的是，因果效应的顺序无法从横断面研究中推断出来。这些结果强调了记录即使是轻度范围内的头部损伤的重要性，因为它们可能与遗传风险相互作用，产生诸如神经退行性疾病等负面的长期健康后果。
