Mild traumatic brain injury is associated with reduced cortical thickness in those at risk for Alzheimer's disease
Mild traumatic brain injury is associated with reduced cortical thickness in those at risk for Alzheimer's disease
复制标题
DOI：
10.1093/brain/aww344
复制
发表时间：
2017-03-01
期刊：
影响因子：
14.5
通讯作者：
Miller, Mark W.
中科院分区：
文献类型：
--
作者：
Hayes, Jasmeet P.;Logue, Mark W.;Miller, Mark W.
中到重度创伤性脑损伤是迟发性阿尔茨海默病等神经退行性疾病发展的最强环境风险因素之一，尽管尚不清楚轻度创伤性脑损伤或脑震荡是否也会带来风险。这项研究考察了轻度创伤性脑损伤和遗传风险作为先前与早期阿尔茨海默病相关的脑区皮质厚度减少的预测因子，以及它们与情景记忆的关系。参与者是160名年龄在19岁到58岁之间的伊拉克和阿富汗战争退伍军人，其中许多人患有轻度创伤性脑损伤和创伤后应激障碍的诊断。阿尔茨海默病发展的全基因组多基因风险分数是使用迄今为止最大的阿尔茨海默病全基因组关联研究的汇总统计数据计算出来的。结果显示，轻度创伤性脑损伤缓和了阿尔茨海默病的遗传风险与皮质厚度之间的关系，因此，轻度创伤性脑损伤和高遗传风险的人在阿尔茨海默病易患区域的皮质厚度降低。在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损伤后时间的函数皮质变薄有关。一项温和的中介分析显示，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患脑区的皮质变薄是记忆表现下降的机制之一。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的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，证明轻度创伤性脑损伤与阿尔茨海默病遗传风险人群中更大的神经退化和记忆能力下降有关，但需要注意的是，从横断面研究中无法推断因果关系的顺序。这些结果强调了记录头部损伤的重要性，即使在轻微范围内也是如此，因为它们可能与遗传风险相互作用，产生负面的长期健康后果，如神经退行性疾病。
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.