Vascular Cognitive Impairment Mechanisms and Therapeutics

Vascular cognitive impairment arises from a spectrum of cerebrovascular pathologies that disrupt blood flow and impair neuronal function. Small vessel disease, endothelial dysfunction and blood–brain barrier breakdown contribute to chronic cerebral hypoperfusion, leading to white matter lesions, lacunar infarcts and cortical microinfarcts. These vascular insults provoke neuroinflammation, oxidative stress and mitochondrial dysfunction, which together exacerbate neuronal loss and synaptic failure. Coexisting amyloid and tau pathologies may further amplify vascular injury, creating a vicious cycle of neurodegeneration. Current management centres on controlling vascular risk factors, such as hypertension, diabetes and hyperlipidaemia, alongside antiplatelet and statin therapies. Emerging strategies aim to modulate neuroinflammatory cascades, protect mitochondrial bioenergetics and restore cerebral perfusion through novel pharmacological agents, lifestyle interventions and digital biomarkers. Advances in neuroimaging and fluid biomarkers enhance early detection and patient stratification, offering pathways to personalised interventions that may attenuate progression and improve cognitive outcomes on a global scale.

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Vascular Cognitive Impairment Mechanisms and Therapeutics publication trend

The graph below shows the total number of articles in vascular cognitive impairment mechanisms and therapeutics across all publications each year (not limited to Nature Index journals).

Technical terms

Chronic cerebral hypoperfusion: Sustained reduction in cerebral blood flow leading to neuronal energy deficits and tissue damage.

Genome-wide association study (GWAS): An analysis method that scans the genome for common genetic variants associated with diseases or traits.

PDK–PDC axis: Regulatory pathway in mitochondria where pyruvate dehydrogenase kinase (PDK) modulates the activity of the pyruvate dehydrogenase complex (PDC), controlling glucose oxidation.

NLRP3 inflammasome: A multiprotein complex that activates inflammatory caspases, promoting maturation and release of proinflammatory cytokines.

Pyroptosis: A form of programmed cell death characterised by inflammasome activation, cell swelling and release of inflammatory mediators.

References

1. Scutellarin Rescued Mitochondrial Damage through Ameliorating Mitochondrial Glucose Oxidation via the Pdk‐Pdc Axis. Advanced Science (2023).
2. A genome‐wide association meta‐analysis of all‐cause and vascular dementia. Alzheimer's & Dementia (2024).
3. ChemR23 activation attenuates cognitive impairment in chronic cerebral hypoperfusion by inhibiting NLRP3 inflammasome-induced neuronal pyroptosis. Cell Death & Disease (2023).