Feng Tianyuyi, Xiao Weizhong, Li Yunfei, Zhao Xiaohu
Department of Radiology, Fifth People's Hospital of Shanghai, Fudan University, 801 Heqing Road, Minhang District, Shanghai 200240, China.
Center of Vascular and interventional Surgery, Department of General Surgery, The Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, 82 Qinglong Street, Qingyang District, Chengdu, Sichuan 610031, China.
Cereb Cortex. 2025 Mar 6;35(3). doi: 10.1093/cercor/bhaf006.
As global population ages, maintaining cognitive health in elderly is crucial. Previous studies suggest a positive link between healthy aging and cognition, but the neural mechanisms remain unclear. This study used genome-wide association studydata to investigate neural mechanisms between healthy aging and cognition. We employed 2-sample Mendelian randomization to evaluate causal relationship between healthy aging (indexed by a multivariate genetic predictor, mvAge) and 6 cognitive measurements. We then used a 2-step Mendelian randomization approach and mediation analysis to identify brain imaging-derived phenotypes potentially mediating this relationship. Mendelian randomization analysis indicated that healthy aging had a positive causal relationship with various cognitive functions (common executive function, intelligence, cognitive performance, and fluid intelligence score). Two-step Mendelian randomization analysis identified 27 brain imaging-derived phenotypes having robust causal relationships with healthy aging and various cognitive measurements. Mediation analysis suggested that volume of subcallosal cortex might mediate effects of healthy aging on all 4 cognitive functions. Volume of cerebellum's VIIb could mediate effects on common executive functions, while fractional anisotropy in the anterior thalamic radiation might mediate effects on intelligence and cognitive performance. These findings suggest that specific brain regions may play a potential mediating role in the relationship between healthy aging and cognitive maintenance.
随着全球人口老龄化，维持老年人的认知健康至关重要。先前的研究表明健康老龄化与认知之间存在正向关联，但神经机制仍不清楚。本研究使用全基因组关联研究数据来探究健康老龄化与认知之间的神经机制。我们采用两样本孟德尔随机化方法来评估健康老龄化（由多变量遗传预测因子mvAge表示）与6种认知测量指标之间的因果关系。然后，我们使用两步孟德尔随机化方法和中介分析来确定可能介导这种关系的脑成像衍生表型。孟德尔随机化分析表明，健康老龄化与各种认知功能（一般执行功能、智力、认知表现和流体智力得分）存在正向因果关系。两步孟德尔随机化分析确定了27种脑成像衍生表型与健康老龄化和各种认知测量指标存在强烈因果关系。中介分析表明，胼胝体下皮质体积可能介导健康老龄化对所有4种认知功能的影响。小脑VIIb的体积可能介导对一般执行功能的影响，而丘脑前辐射的分数各向异性可能介导对智力和认知表现的影响。这些发现表明，特定脑区可能在健康老龄化与认知维持之间的关系中发挥潜在的中介作用。
