Apolipoprotein E (APOE) ε4 Status Moderates the Relationship Between Close-Range Blast Exposure and Cognitive Functioning.
Apolipoprotein E (APOE) ε4 Status Moderates the Relationship Between Close-Range Blast Exposure and Cognitive Functioning.
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载脂蛋白 E (APOE) γ4 状态调节近距离爆炸暴露与认知功能之间的关系。
DOI：
10.1017/s1355617720001034
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Esterman,Michael
中科院分区：
文献类型：
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作者：
Wooten,Thomas;Sullivan,DanielleR;Logue,MarkW;Fonda,JenniferR;Fortier,CatherineB;DeGutis,Joseph;McGlinchey,Regina;Milberg,William;Esterman,Michael
目标最近的研究表明，近距离爆炸暴露（CBE），无论急性脑震荡症状如何，都可能对大脑健康和认知产生长期负面影响；然而，这些影响因人而异。载脂蛋白 (APOE) ε4 等位基因的遗传是一种可能影响恢复并解释爆炸损伤长期认知结果异质性的潜在遗传风险因素，这是众所周知的阿尔茨海默病遗传风险因素。我们假设 APOE ε4 携带者状态会减轻 CBE 对长期认知结果的影响。方法为了检验这一假设，我们检查了 488 名 9/11 后退伍军人，他们完成了神经心理功能、精神病诊断、爆炸暴露史、军事和非军事轻度创伤性脑损伤 (mTBI) 和可用 APOE 基因型的评估。我们分别研究了 CBE 对有和没有 APOE ε4 等位基因的个体的注意力、记忆和执行功能的影响。结果正如预测的那样，我们观察到 CBE 状态对认知的不同影响是 APOE ε4 状态的函数，其中 CBE ε4 携带者表现出明显更差的神经心理学表现，特别是在记忆领域。在调整临床、人口和遗传因素后，这些结果仍然存在，并且在检查其他神经创伤变量（即终身或军事 mTBI、远距离爆炸暴露）时没有观察到，尽管这些变量显示出相似的趋势。结论这些结果表明 APOE ε4 携带者更容易受到 CBE 对认知的影响，并强调在研究神经创伤的认知影响时考虑遗传风险的重要性。
ObjectivesRecent studies suggest that close-range blast exposure (CBE), regardless of acute concussive symptoms, may have negative long-term effects on brain health and cognition; however, these effects are highly variable across individuals. One potential genetic risk factor that may impact recovery and explain the heterogeneity of blast injury’s long-term cognitive outcomes is the inheritance of an apolipoprotein (APOE) ε4 allele, a well-known genetic risk factor for Alzheimer’s disease. We hypothesized that APOE ε4 carrier status would moderate the impact of CBE on long-term cognitive outcomes.MethodsTo test this hypothesis, we examined 488 post-9/11 veterans who completed assessments of neuropsychological functioning, psychiatric diagnoses, history of blast exposure, military and non-military mild traumatic brain injuries (mTBIs), and available APOE genotypes. We separately examined the effects of CBE on attention, memory, and executive functioning in individuals with and without the APOE ε4 allele.ResultsAs predicted, we observed a differential impact of CBE status on cognition as a function of APOE ε4 status, in which CBE ε4 carriers displayed significantly worse neuropsychological performance, specifically in the domain of memory. These results persisted after adjusting for clinical, demographic, and genetic factors and were not observed when examining other neurotrauma variables (i.e., lifetime or military mTBI, distant blast exposure), though these variables displayed similar trends.ConclusionsThese results suggest APOE ε4 carriers are more vulnerable to the impact of CBE on cognition and highlight the importance of considering genetic risk when studying cognitive effects of neurotrauma.