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

Topic: Risk, prevention and care in population studies

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 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. 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.

@article{lv2025-41110565,
  author  = {Lv, Hongxiao and Liu, Yutong and Yang, Xinyu and Xu, Xi-Qi and Zhou, Junwei and Yu, Wentao},
  title   = {{Research progress on the role of oxidative stress in the pathogenesis of vascular dementia and its treatment}},
  journal = {Journal of Stroke and Cerebrovascular Diseases},
  year    = {2025},
  doi     = {10.1016/j.jstrokecerebrovasdis.2025.108475},
  pmid    = {41110565},
  url     = {https://doi.org/10.1016/j.jstrokecerebrovasdis.2025.108475}
}

Key findings

• 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 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.

Why it matters

This review describes how oxidative stress contributes to vascular dementia through mechanisms including mitochondrial dysfunction and impaired antioxidant pathways, and discusses therapeutic strategies from traditional antioxidants to newer approaches. It provides a theoretical framework for treatment but does not report results from a clinical trial.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1016/j.jstrokecerebrovasdis.2025.108475
• PubMed: 41110565
• Original source →
• Free full text: Journal of Stroke and Cerebrovascular Diseases →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

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