Li Tengfei, Chen Jie, Zhao Bingxin, Garden Gwenn A, Giovanello Kelly S, Wu Guorong, Zhu Hongtu
Biomedical Research Imaging Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Radiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
medRxiv. 2024 Sep 2:2024.08.05.24311482. doi: 10.1101/2024.08.05.24311482.
Nonlinear changes in brain function during aging are shaped by a complex interplay of factors, including sex, age, genetics, and modifiable health risk factors. However, the combined effects and underlying mechanisms of these factors on brain functional connectivity remain poorly understood.
To comprehensively investigate the combined associations of sex, age, genotypes, and ten common modifiable health risk factors with brain functional connectivities during aging.
This analysis used data from 36,630 UK Biobank participants, aged 44-81, who were assessed for sex, age, genotypes, 10 health risk factors, and brain functional connectivities through resting-state functional magnetic resonance imaging.
Brain functional connectivities were evaluated through within- and between-network functional connectivities and connectivity strength. Associations between risk factors and brain functional connectivities, including their interaction effects, were analyzed.
Hypertension, BMI, and education were the top three influential factors. Sex-specific effects were also observed in interactions involving APOE4 gene, smoking, alcohol consumption, diabetes, BMI, and education. Notably, a negative sex-excessive alcohol interaction showed a stronger negative effect on functional connectivities in males, particularly between the dorsal attention network and the language network, while moderate alcohol consumption appeared to have protective effects. A significant negative interaction between sex and revealed a greater reduction in functional connectivity between the cingulo-opercular network and the posterior multimodal network in male carriers. Additional findings included a negative age-BMI interaction between the visual and dorsal attention networks, and a positive age-hypertension interaction between the frontoparietal and default mode networks.
The findings highlight significant sex disparities in the associations between age, the -ε4 gene, modifiable health risk factors, and brain functional connectivity, emphasizing the necessity of jointly considering these factors to gain a deeper understanding of the complex processes underlying brain aging.
衰老过程中大脑功能的非线性变化受到多种因素复杂相互作用的影响，这些因素包括性别、年龄、基因以及可改变的健康风险因素。然而，这些因素对大脑功能连接的综合影响及潜在机制仍知之甚少。
全面研究性别、年龄、基因型和十种常见可改变的健康风险因素在衰老过程中与大脑功能连接的综合关联。
设计、设置和参与者：本分析使用了来自英国生物银行36630名年龄在44 - 81岁参与者的数据，这些参与者通过静息态功能磁共振成像评估了性别、年龄、基因型、10种健康风险因素和大脑功能连接。
通过网络内和网络间的功能连接以及连接强度评估大脑功能连接。分析了风险因素与大脑功能连接之间的关联，包括它们的交互作用。
高血压、体重指数（BMI）和教育程度是前三大影响因素。在涉及APOE4基因、吸烟、饮酒、糖尿病、BMI和教育程度的交互作用中也观察到了性别特异性效应。值得注意的是，性别与过量饮酒的负向交互作用对男性的功能连接有更强的负面影响，特别是在背侧注意网络和语言网络之间，而适度饮酒似乎具有保护作用。性别与[此处原文缺失相关基因或因素]之间的显著负向交互作用表明，男性携带者的扣带回 - 岛叶网络和后多模态网络之间的功能连接减少幅度更大。其他发现包括视觉和背侧注意网络之间的年龄 - BMI负向交互作用，以及额顶叶和默认模式网络之间的年龄 - 高血压正向交互作用。
研究结果突出了年龄、ε4基因、可改变的健康风险因素与大脑功能连接之间关联存在显著的性别差异，强调了联合考虑这些因素以更深入理解大脑衰老潜在复杂过程的必要性。
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