Neuroplasticity and Brain Rewiring in Vascular Dementia: Mechanisms, Therapeutic Strategies, and Biomarker Insights

Background: Vascular dementia (VaD) arises from cerebrovascular insults, chronic hypoperfusion, infarcts, and microbleeds that disrupt perfusion and blood–brain barrier integrity, leading to progressive cognitive decline. Recent insights into amyloid-β (Aβ)-induced endothelial leakiness, oxidative stress, and inflammatory pathways suggest both impairments and compensatory neuroplastic adaptations.Methods: We conducted a narrative review of studies (2020–2025) drawn from PubMed and Google Scholar using terms such as “vascular dementia,” “neuroplasticity,” “amyloid leakiness,” “Nrf2/HO-1,” “exercise,” and “cognitive training.” Key experimental models, clinical trials, and high-impact journal articles were synthesized.Results: Cerebrovascular injury triggers angiogenesis, synaptogenesis, and limited adult neurogenesis through BDNF, VEGF, and IGF-1 upregulation (Choi et al., 2016; Song, 2024). Soluble Aβ oligomers elicit endothelial leakiness by disrupting VE-cadherin junctions (Li et al., 2024). Oxidative markers (MDA, 4-HNE) and inflammatory cytokines further impair synaptic plasticity (Kuang, Zhang, & Li, 2021). Interventions, including aerobic exercise, cognitive rehabilitation, and antioxidants (α-lipoic acid, edaravone, melatonin)—activate the Nrf2/HO-1 pathway, reduce reactive oxygen species, and preserve synaptic integrity (Tang, Huang, & Zhao, 2019; Wu, Zhao, & Liu, 2024). Emerging therapies such as mitochondrial transfer, low-intensity focused ultrasound, and apelin receptor modulation show preclinical promise.Conclusions: Despite chronic ischemia, the VaD brain retains substantial neuroplastic potential. Multimodal strategies that combine vascular risk management with targeted plasticity-promoting interventions, guided by biomarkers such as serum BDNF and neuroimaging connectivity, may slow or reverse cognitive decline in vascular dementia.