Multifaceted role of nitric oxide in vascular dementia

Vascular dementia is a highly heterogeneous neurodegenerative disorder induced by a variety of factors. Currently, there are no definitive treatments for the cognitive dysfunction associated with vascular dementia. However, early detection and preventive measures have proven effective in reducing the risk of onset and improving patient prognosis. Nitric oxide plays an integral role in various physiological and pathological processes within the central nervous system. In recent years, nitric oxide has been implicated in the regulation of synaptic plasticity and has emerged as a crucial factor in the pathophysiology of vascular dementia. At different stages of vascular dementia, nitric oxide levels and bioavailability undergo dynamic alterations, with a marked reduction in the later stages, which significantly contributes to the cognitive deficits associated with the disease. This review provides a comprehensive review of the emerging role of nitric oxide in the physiological and pathological processes underlying vascular dementia, focusing on its effects on synaptic dysfunction, neuroinflammation, oxidative stress, and blood‒brain barrier integrity. Furthermore, we suggest that targeting the nitric oxide soluble guanylate cyclase-cyclic guanosine monophosphate pathway through specific therapeutic strategies may offer a novel approach for treating vascular dementia, potentially improving both cognitive function and patient prognosis. The review contributes to a better understanding of the multifaceted role of nitric oxide in vascular dementia and to offering insights into future therapeutic interventions.