Mechanisms and biomarkers of poststroke cognitive impairment

ABSTRACT: Poststroke cognitive impairment is a common neurological complication in stroke patients, characterized by progressive cognitive decline ranging from mild cognitive impairment to vascular dementia, significantly impacting patients' quality of life and long-term prognosis. Recent studies have gradually unveiled the multidimensional pathophysiological mechanisms underlying post-stroke cognitive impairment. This review provides a detailed introduction to the mechanisms and biomarkers of poststroke cognitive impairment. At the molecular level, the development of poststroke cognitive impairment involves multi-level and interconnected pathophysiological changes. Among these, the activation of neuroinflammation and oxidative stress damage are considered key initiating factors. Concurrently, the accumulation of reactive oxygen species induced by oxidative stress can further promote the occurrence of poststroke cognitive impairment. Increased blood-brain barrier permeability, along with the infiltration of peripheral inflammatory cells and the entry of toxic substances into the brain, exacerbates neural damage. In terms of neurotransmitter systems, the imbalance between excitatory and inhibitory neurotransmitter systems directly affects synaptic plasticity and the integration of neural networks. Structurally, the integrity of white matter microstructure is compromised, manifesting as myelin loss and axonal transport impairment. These multi-level pathological changes interact through complex positive feedback mechanisms, collectively forming the pathogenic network of poststroke cognitive impairment. In the field of biomarker research, a six-dimensional classification system for post-stroke cognitive impairment biomarkers has been reported, systematically categorizing relevant biomarkers into metabolic markers, inflammatory factor profiles, genetic markers, blood-brain barrier damage indicators, gut microbiota characteristics, and neuroimaging biomarkers. Notably, the integrated predictive model developed by combining serum biomarkers with multimodal neuroimaging features significantly enhances the diagnostic specificity of poststroke cognitive impairment biomarkers. This multidimensional and systematic research approach provides new perspectives for the in-depth analysis of the pathogenesis of poststroke cognitive impairment biomarkers and offers important targets for early clinical intervention. In the future, it is hoped that dynamic monitoring of the temporal changes in these biomarkers can more accurately assess the effectiveness of interventions and guide the optimization and adjustment of treatment plans. Based on risk assessment results, a tiered management approach should be implemented: high-risk patients should undergo cognitive assessments and biomarker testing every three months, while moderate-to-low-risk patients should follow a stepwise monitoring protocol. This precision management model can predict the risk of cognitive decline up to 6-12 months in advance, enabling timely interventions to reduce the incidence of severe cognitive impairment. Mechanistic studies and biomarker discovery for poststroke cognitive impairment have brought breakthrough progress to clinical diagnosis and treatment. Future research should continue to explore its molecular mechanisms, develop more effective targeted therapeutic drugs, establish a comprehensive early warning and personalized treatment system, and ultimately achieve precise prevention, control, and optimized management of poststroke cognitive impairment.