Figure 2.

Pathophysiology of vascular cognitive impairment (VCI). Chronic cerebral hypoperfusion (CCH) plays a central role in the complex pathophysiology of VCI, by inducing energy and oxygen deficiency within the brain. CCH causes an energy imbalance, thereby triggering oxidative stress, endoplasmic reticulum stress, and mitochondrial dysfunction. Together, these pathologies contribute to a compromised blood-brain barrier (BBB) integrity, neuroinflammation, white matter (WM) lesions, and neurodegeneration. Under normal physiological conditions, BBB functions as a selective semipermeable and dynamic interface, crucial for cerebral homeostasis. However, under CCH, its integrity is disrupted, leading to an increased movement of substances between the blood and the brain. The overactivation of glial cells, referred to as neuroinflammation, plays a pivotal role in the pathophysiology of VCI. Additionally, CCH induces damage to the myelin sheath, and the subsequent loss of myelin can impede the propagation of action potentials, eventually resulting in axonal loss and neuronal depletion. These pathological changes culminate in the manifestation of symptoms associated with vascular dementia, including cognitive impairment, memory loss, and other related manifestations.