皮质醇觉醒反应和Val66Met BDNF多态性相互作用，塑造衰老过程中的言语流畅性
Cortisol awakening response and Val66Met BDNF polymorphism interact to shape verbal fluency in aging.
摘要(中文译文)
神经可塑性是认知功能的核心基础。在整个生命周期中，与年龄相关的神经可塑性变化在高阶认知能力中尤为明显。其中，言语流畅性（verbal fluency, VF）被认为是认知老化的敏感标志物，因为它反映了语言系统和执行控制系统的高效运作。言语流畅性通常被区分为两个子领域：音位言语流畅性（phonemic verbal fluency, PVF），依赖于执行功能和前额叶皮层活动；以及语义言语流畅性（semantic verbal fluency, SVF），更依赖于词汇-语义网络和联想提取过程。神经可塑性受神经营养和神经内分泌机制的双重影响。因此，一方面，脑源性神经营养因子（Brain-Derived Neurotrophic Factor, BDNF）Val66Met基因多态性调节突触可塑性，其中Met等位基因与BDNF分泌减少及更高的认知脆弱性相关。另一方面，皮质醇觉醒反应（Cortisol Awakening Response, CAR）与前额叶效率和执行控制有关。本研究考察了健康老年人中CAR与BDNF Val66Met基因多态性之间的交互作用及其与PVF和SVF的关系。结果显示，BDNF Val66Met基因多态性在CAR-PVF关系中具有显著的调节效应：仅在Val纯合子参与者中，较高的CAR与更好的表现相关。未发现与SVF的显著关联。这些发现凸显了认知老化如何受到控制内分泌和神经营养功能的遗传与激素因素之间复杂交互作用的影响。
Abstract
Neural plasticity is central for cognitive functioning. Across the lifespan, age-related changes in neural plasticity are particularly evident in higher-order cognitive abilities. Among these, verbal fluency (VF) is considered a sensitive marker of cognitive aging, as it reflects the efficient function of both language and executive control systems. VF is commonly differentiated into two subdomains: phonemic verbal fluency (PVF), which depends on executive functions and prefrontal cortex activity, and semantic verbal fluency (SVF), which relies more strongly on lexical-semantic networks and associative retrieval processes. Neural plasticity is influenced by both neurotrophic and neuroendocrine mechanisms. Thus, on the one hand, the Brain-Derived Neurotrophic Factor (BDNF) Val66Met polymorphism modulates synaptic plasticity, with the Met allele being associated with reduced BDNF secretion and greater cognitive vulnerability. On the other hand, the Cortisol Awakening Response (CAR) has been linked to prefrontal efficiency and executive control. This study examined the interaction between CAR and the BDNF Val66Met polymorphism in relation to PVF and SVF in healthy older adults. Results showed a significant moderating effect of the BDNF Val66Met polymorphism in the CAR-PVF relationship: greater CAR was associated with better performance only in Val-homozygous participants. No significant associations were found for SVF. These findings highlight how cognitive aging is shaped by a complex interplay between genetic and hormonal factors controlling endocrine and neurotrophin functions.
如何引用
AMA
Pablo Rivas-Diaz, David Trillo-Figueroa, Teresa Peiró, Javier David-Lluesma, Olga Rivero, Noemi SanMiguel, et al. Cortisol awakening response and Val66Met BDNF polymorphism interact to shape verbal fluency in aging.. Psychoneuroendocrinology. 2026; doi:10.1016/j.psyneuen.2026.107956.
APA
Pablo Rivas-Diaz, David Trillo-Figueroa, Teresa Peiró, Javier David-Lluesma, Olga Rivero, Noemi SanMiguel, et al (2026). Cortisol awakening response and Val66Met BDNF polymorphism interact to shape verbal fluency in aging.. Psychoneuroendocrinology. https://doi.org/10.1016/j.psyneuen.2026.107956
GB/T 7714
Pablo Rivas-Diaz, David Trillo-Figueroa, Teresa Peiró, Javier David-Lluesma, Olga Rivero, Noemi SanMiguel, et al. Cortisol awakening response and Val66Met BDNF polymorphism interact to shape verbal fluency in aging.[J]. Psychoneuroendocrinology, 2026 doi:10.1016/j.psyneuen.2026.107956.
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