Molecular mechanisms of cognitive impairment associated with stroke

Stroke is the second leading cause of death after coronary heart disease in developed countries and is the greatest cause of disability and cognitive impairment. Risk factors for cognitive impairment and dementia after stroke are multifactorial including older age, family history, hypertension, arterial fibrillation, diabetes, genetic variants, low educational status, vascular comorbidities, prior transient ischaemic attack or recurrent stroke, depressive illness duration of a stroke, location, volume, intensity, and degree of neuronal degeneration, location and size of infarction after stroke, time interval after stroke other cerebral dysfunctions. The pathophysiology of stroke associated cognitive impairment is complex and recent molecular, cellular, and animal models studies have revealed that multiple cellular changes have been implicated, including altered redox state, mitochondrial dysfunction, disruption of the blood-brain barrier, perivascular spacing, glymphatic system impairment, microglia activation and amyloid-β deposition in the parenchyma of the brain. These studies have also evidenced the involvement of various transcription factors, intracellular adhesion molecules, and endogenous growth factors in the pathogenesis of cognitive impairment associated with stroke and providing scope for developing therapeutic strategies for treatment. This review summarizes the latest research findings on molecular mechanisms involved in cognitive impairment associated with stroke.