Zhang Xin, Wang Zhen, Zou Jing, Zhang Le, Ning Jing-Hua, Jiang Bei, Liang Yi, Zhang Yu-Zhe
College of Basic Medical Sciences, Dali University, Dali, Yunnan, China.
The First Affiliated Hospital of Dali University, Dali, Yunnan, China.
Front Aging Neurosci. 2024 May 22;16:1395553. doi: 10.3389/fnagi.2024.1395553. eCollection 2024.
Physical weakness is associated with cortical structures, but the exact causes remain to be investigated. Therefore, we utilized Mendelian randomization (MR) analysis to uncover the underlying connection between frailty and cortical structures.
The Genome-Wide Association Study (GWAS) on frailty pooled data from publicly available sources such as the UK Biobank and included five indicators of frailty: weakness, walking speed, weight loss, physical activity, and exhaustion. GWAS data on cerebral cortical structure were obtained from the ENIGMA consortium, and we assessed the causal relationship between hereditary frailty and cortical surface area (SA) or cortical thickness (TH). Inverse variance weighting (IVW) was used as the primary estimate, and heterogeneity and multidimensionality were monitored by MR-PRESSO to detect outliers. Additionally, MR-Egger, Cochran's Q test, and weighted median were employed.
At the aggregate level, there was no causal relationship between frailty and cortical thickness or surface area. At the regional level, frailty was associated with the thickness of the middle temporal lobe, parahippocampus, rostral middle frontal lobe, lower parietal lobe, anterior cingulate gyrus, upper temporal lobe, lateral orbital frontal cortex, pericardial surface area, rostral middle frontal lobe, upper temporal lobe, rostral anterior cingulate gyrus, lower parietal lobe, and upper parietal lobe. These results were nominally significant, and sensitivity analyses did not detect any multidirectionality or heterogeneity, suggesting that the results of our analyses are reliable.
The results of our analyses suggest a potential causal relationship between somatic weakness and multiple regions of cortical structure. However, the specific mechanisms of influence remain to be investigated. Preliminary results from our analysis suggest that the effects of physical frailty on cortical structures are influenced by various factors related to frailty exposure. This relationship has been documented, and it is therefore both feasible and meaningful to build on existing research to explore the clinical significance of the relationship.
身体虚弱与皮质结构有关，但其确切原因仍有待研究。因此，我们利用孟德尔随机化（MR）分析来揭示虚弱与皮质结构之间的潜在联系。
关于虚弱的全基因组关联研究（GWAS）汇总了来自英国生物银行等公开可用来源的数据，并纳入了五个虚弱指标：虚弱、步行速度、体重减轻、身体活动和疲惫。大脑皮质结构的GWAS数据来自ENIGMA联盟，我们评估了遗传性虚弱与皮质表面积（SA）或皮质厚度（TH）之间的因果关系。采用逆方差加权（IVW）作为主要估计方法，并通过MR-PRESSO监测异质性和多维度性以检测异常值。此外，还使用了MR-Egger、 Cochr an检验和加权中位数。
在总体水平上，虚弱与皮质厚度或表面积之间没有因果关系。在区域水平上，虚弱与颞中回、海马旁回、额中回前部、顶叶下部、前扣带回、颞上回、眶额外侧皮质、心包表面积、额中回前部、颞上回、扣带回前部、顶叶下部和顶叶上部的厚度有关。这些结果具有名义上的显著性，敏感性分析未检测到任何多方向性或异质性，表明我们的分析结果是可靠的。
我们的分析结果表明身体虚弱与多个皮质结构区域之间存在潜在的因果关系。然而，具体的影响机制仍有待研究。我们分析的初步结果表明，身体虚弱对皮质结构的影响受与虚弱暴露相关的各种因素影响。这种关系已有文献记载，因此在现有研究基础上探索这种关系的临床意义既可行又有意义。
