Li Yuna, Tian Shan, Qiao Yuan, Cong Chaohua, Yang Junting, Cao Shanshan, Zhu Xirui, Zhao Lei, Li Panlong, Su Jingjing
Department of Neurology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
School of Electrical and Information Engineering, Zhengzhou University of Light Industry, Zhengzhou, China.
J Cachexia Sarcopenia Muscle. 2025 Jun;16(3):e13833. doi: 10.1002/jcsm.13833.
White matter hyperintensity (WMH) is one of the key imaging markers of cerebral small vessel disease (CSVD) and white matter microstructural injury may occur earlier than WMH. However, the associations of handgrip strength (HGS) and serum total testosterone (STT) with WMH and microstructural injury have not been thoroughly investigated. Therefore, we aimed to explore the associations of HGS and STT with WMH and microstructural injury, measured by fractional anisotropy (FA), mean diffusivity (MD), intracellular volume fraction (ICVF), and isotropic volume fraction (ISOVF).
A total of 34 832 participants from the UK Biobank (aged 64.15 ± 7.75 years, 50.9% male) were included in the study. Cross-sectional analyses were conducted using three linear regression models to assess the relationships between HGS, STT and neuroimaging outcomes. Sensitivity analyses were performed to validate the robustness of the linear regression results. Longitudinal, mediation and Mendelian randomization (MR) analyses were conducted to explore the longitudinal impact of HGS on WMH, the mediating effects of STT between HGS and neuroimaging outcomes, and probable causal relationships between HGS, STT and WMH.
A greater HGS was linearly associated with a smaller WMH volume (β = -0.006642, p < 0.001) and fuller microstructure (p < 0.001). These relationships persisted when stratified by sex or age decade and were supported by the results of the longitudinal analysis (β = -26.4, p = 0.0145). In females, STT was found to be linearly negatively related to WMH volume (β = -0.109, p < 0.001), MD and ISOVF, and linearly positively related to FA and ICVF (p < 0.001). In males, STT was linearly negatively linked to WMH volume (β = -0.016, p < 0.001) and MD (β = -1.6 , p = 0.007), and positively associated to ICVF (β = 0.00012, p = 0.043). STT mediated the association between HGS and WMH volume (mediation proportion: 1.06% in males and 1.57% in females), and the possible causality was suggested for males through MR analysis: the positive causality between HGS and STT (p = 0.0394) and the negative causality between STT and WMH (p = 0.0787).
Our study revealed that greater HGS was linearly associated with reduced WMH volume and less white matter microstructural injury, mediated by STT. Improving muscle function may contribute to deferring white matter damage and preventing stroke and dementia, offering a feasible secondary prevention measure for CSVD.
白质高信号（WMH）是脑小血管病（CSVD）的关键影像学标志物之一，白质微观结构损伤可能早于WMH出现。然而，握力（HGS）和血清总睾酮（STT）与WMH及微观结构损伤之间的关联尚未得到充分研究。因此，我们旨在探讨HGS和STT与WMH及微观结构损伤之间的关联，微观结构损伤通过分数各向异性（FA）、平均扩散率（MD）、细胞内体积分数（ICVF）和各向同性体积分数（ISOVF）来衡量。
本研究纳入了英国生物银行的34832名参与者（年龄64.15±7.75岁，50.9%为男性）。使用三个线性回归模型进行横断面分析，以评估HGS、STT与神经影像学结果之间的关系。进行敏感性分析以验证线性回归结果的稳健性。进行纵向、中介和孟德尔随机化（MR）分析，以探讨HGS对WMH的纵向影响、STT在HGS与神经影像学结果之间的中介作用，以及HGS、STT与WMH之间可能的因果关系。
较高的HGS与较小的WMH体积（β = -0.006642，p < 0.001）和更完整的微观结构（p < 0.001）呈线性相关。按性别或年龄十年分层时，这些关系依然存在，并得到纵向分析结果的支持（β = -26.4，p = 0.0145）。在女性中，发现STT与WMH体积（β = -0.109，p < 0.001）、MD和ISOVF呈线性负相关，与FA和ICVF呈线性正相关（p < 0.001）。在男性中，STT与WMH体积（β = -0.016，p < 0.001）和MD（β = -1.6 ，p = 0.007）呈线性负相关，与ICVF呈正相关（β = 0.00012，p = 0.043）。STT介导了HGS与WMH体积之间的关联（中介比例：男性为1.06%，女性为1.57%），并且通过MR分析提示男性可能存在因果关系：HGS与STT之间的正向因果关系（p = 0.0394）以及STT与WMH之间的负向因果关系（p = 0.0787）。
我们的研究表明，较高的HGS与减少的WMH体积和较轻的白质微观结构损伤呈线性相关，由STT介导。改善肌肉功能可能有助于延缓白质损伤并预防中风和痴呆，为CSVD提供了一种可行的二级预防措施。
