Research progress on the role of oxidative stress in the pathogenesis of vascular dementia and its treatment

BACKGROUND: Vascular dementia (VaD) is the second most common type of dementia after Alzheimer's disease, imposing a substantial burden on global health. Accumulating evidence indicates that oxidative stress, characterized by an imbalance between reactive oxygen species (ROS) production and antioxidant defense, plays a pivotal role in the pathogenesis of VaD. OBJECTIVE: This review aims to summarize the latest research progress on the involvement of oxidative stress in the pathogenesis of VaD and explore emerging therapeutic strategies targeting oxidative stress. RESULTS: Oxidative stress is deeply involved in multiple pathological processes of VaD. Its root cause lies in chronic cerebral hypoperfusion (CCH), which leads to mitochondrial dysfunction(definition) and excessive ROS production. Such oxidative damage exacerbates blood-brain barrier (BBB) disruption, neuroinflammation, and neuronal apoptosis, ultimately resulting in cognitive decline. Key molecular mechanisms include the activation of NADPH oxidase, impairment of the Nrf2 antioxidant pathway, and dysregulation of SIRT1. Therapeutic strategies have evolved from traditional antioxidants (e.g., α-lipoic acid) to novel approaches, including targeting the Nrf2/HO-1 pathway (e.g., using saffron-rich GJ-4 extract), regulating mitochondrial function, utilizing natural compounds (e.g., resveratrol acting via SIRT1 activation), and non-pharmacological interventions such as acupuncture. These strategies alleviate oxidative stress through multi-target mechanisms and have demonstrated significant efficacy. CONCLUSION: The central role of oxidative stress in VaD provides new targets for treatment, but a shift from single-target antioxidant therapy to multi-level intervention is required. Future research should focus on developing targeted antioxidant therapies, exploring combination treatment regimens, and validating biomarkers applicable for early detection and therapeutic efficacy assessment.