Systemic inflammation as a predictor of brain aging: Contributions of physical activity, metabolic risk, and genetic risk.
Systemic inflammation as a predictor of brain aging: Contributions of physical activity, metabolic risk, and genetic risk.
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DOI：
10.1016/j.neuroimage.2017.12.027
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发表时间：
2018-05-15
期刊：
影响因子：
5.7
通讯作者：
Braskie MN
中科院分区：
文献类型：
--
作者：
Corlier F;Hafzalla G;Faskowitz J;Kuller LH;Becker JT;Lopez OL;Thompson PM;Braskie MN
炎症过程可能导致阿尔茨海默病（AD）和年龄相关性脑退化的风险。代谢和遗传风险因素以及体力活动可能反过来影响这些炎症过程。其中一些风险因素是可以改变的，并且相互作用。了解这些过程如何共同与大脑衰老相关，将有助于为未来治疗或预防认知衰退的干预措施提供信息。我们使用脑磁共振成像（MRI）扫描335名老年人（平均年龄77.3 ± 3.4岁），他们在9年的纵向研究期间保持非痴呆状态。我们使用结构方程模型（SEM）在226名成年人的一个子集，以评估是否基线外周炎症（血清C反应蛋白水平; CRP）的措施，介导的遗传和代谢风险的基线贡献，和体力活动，在研究第9年的AD相关的大脑区域的区域皮质厚度。我们发现，基线代谢风险和AD风险变异体载脂蛋白E ε4（APOE 4）均调节基线血清CRP。更高的基线CRP水平，反过来，预测薄的区域皮质在第9年，并介导高代谢风险和薄皮质在这些地区之间的影响。由免疫相关AD风险基因（APOE除外）变体组成的较高多基因风险评分与较薄的区域皮质相关。然而，CRP水平并没有介导这种作用，这表明其他机制可能是负责AD风险升高。我们发现了遗传和环境因素与结构性大脑健康之间的相互作用。我们的研究结果支持代谢风险和外周炎症在年龄相关性脑衰退中的作用。
Inflammatory processes may contribute to risk for Alzheimer's disease (AD) and age-related brain degeneration. Metabolic and genetic risk factors, and physical activity may, in turn, influence these inflammatory processes. Some of these risk factors are modifiable, and interact with each other. Understanding how these processes together relate to brain aging will help to inform future interventions to treat or prevent cognitive decline. We used brain magnetic resonance imaging (MRI) to scan 335 older adult humans (mean age 77.3 ± 3.4 years) who remained non-demented for the duration of the 9-year longitudinal study. We used structural equation modeling (SEM) in a subset of 226 adults to evaluate whether measures of baseline peripheral inflammation (serum C-reactive protein levels; CRP), mediated the baseline contributions of genetic and metabolic risk, and physical activity, to regional cortical thickness in AD-relevant brain regions at study year 9. We found that both baseline metabolic risk and AD risk variant apolipoprotein E ε4 (APOE4), modulated baseline serum CRP. Higher baseline CRP levels, in turn, predicted thinner regional cortex at year 9, and mediated an effect between higher metabolic risk and thinner cortex in those regions. A higher polygenic risk score composed of variants in immune-associated AD risk genes (other than APOE) was associated with thinner regional cortex. However, CRP levels did not mediate this effect, suggesting that other mechanisms may be responsible for the elevated AD risk. We found interactions between genetic and environmental factors and structural brain health. Our findings support the role of metabolic risk and peripheral inflammation in age-related brain decline.
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