Major pathogenic mechanisms in vascular dementia: Roles of cellular stress response and hormesis in neuroprotection

Vascular dementia (VaD), considered the second most commoncause of cognitive impairment after Alzheimer diseasein the elderly, involves the impairment of memory and cognitivefunction as a consequence of cerebrovascular disease.Chronic cerebral hypoperfusion is a common pathophysiologicalcondition frequently occurring in VaD. It is generallyassociated with neurovascular degeneration, in which neuronaldamage and blood-brain barrier alterations coexistand evoke beta-amyloid–induced oxidative and nitrosativestress, mitochondrial dysfunction, and inflammasome- promotedneuroinflammation, which contribute to and exacerbatethe course of disease. Vascular cognitive impairmentcomprises a heterogeneous group of cognitive disorders ofvarious severity and types that share a presumed vascularetiology. The present study reviews major pathogenic factorsinvolved in VaD, highlighting the relevance of cerebrocellularstress and hormetic responses to neurovascularinsult, and addresses these mechanisms as potentially viableand valuable as foci of novel neuroprotective methodsto mitigate or prevent VaD.