<p>Vascular cognitive impairment: pathophysiological mechanisms, insights into structural basis, and perspectives in specific treatments</p>

Abstract

Vascular cognitive impairment (VCI) and vascular dementia are the most common forms of cognitive disorder associated with cerebrovascular disease and related to increased morbidity and mortality among the older population. Growing evidence suggests the contribution of blood-pressure variability, cardiac arrhythmia, hyperactivation of the renin–angiotensin–aldosterone system, endothelial dysfunction, vascular remodeling and stiffness, different angiopathies, neural tissue homeostasis, and systemic metabolic disorders to the pathophysiology of VCI. In this review, we focus on factors contributing to cerebrovascular disease, neurovascular unit alterations, and novel approaches to cognitive improvement in patients with cognitive decline. One of the important factors associated with the neuronal causes of VCI is the S100B protein, which can affect the expression of cytokines in the brain, support homeostasis, and regulate processes of differentiation, repair, and apoptosis of the nervous tissue. Since the pathological basis of VCI is complex and diverse, treatment affecting the mechanisms of cognitive disorders should be developed. The prospective role of a novel complex drug consisting of released–active antibodies to S100 and to endothelial NO synthase in VCI treatment is highlighted.

Update on the Neurobiology of Vascular Cognitive Impairment: From Lab to Clinic

“…As markers of neuroinflammation and immune surveillance within the central nervous system (CNS), microglial cells resulted to be activated in MCI patients evolving in VaD [23]. These patients also demonstrated abnormalities of proteins involved in extracellular matrix synthesis/degradation, angiogenesis, axonal damage, hemostatic processes, and inflammatory responses [1,17,22].…”

“…Vascular cognitive impairment (VCI) is considered as an "umbrella term" including a wide spectrum of cognitive disorders due to cerebrovascular disease of different etiologies, including large or strategic stroke, subcortical ischemic vascular disease (SIVD), multi-infarct strokes, border-zone ischemia, and intracerebral hemorrhages (especially large bleeding and multiple cortical and/or subcortical microbleeds) [1,2]. As such, VCI encompasses any degree of cognitive decline, ranging from the impairment of a single cognitive domain (mild VCI) to an overt vascular dementia (VaD) or mixed dementia (vascular and degenerative, most commonly of Alzheimer's type) [3].…”

“…To date, the exact neurochemical basis underlying VCI is not completely clarified, although increasing evidence suggests that different components, i.e., oxidative stress, neuroinflammation, endothelial dysfunction, neurotransmitter imbalance, and cortical hyperexcitability play a role [1,2]. A better understanding of these mechanisms would be helpful for a more accurate identification and differential diagnosis of these patients, as well as for the development of evidence-based drugs and customized non-pharmacological treatments targeting specific markers of disease.…”

Association between Peripheral Blood Inflammatory Markers, Endothelial Dysfunction Markers, and Depression

“…Abs to S100 inhibited the induction of LPT, whereas RAF of Abs to S100 offset this inhibiting activity [48] Influence on electrical properties of cell membranes Isolated neurons of Helix pomatia RAF of Abs to S100 suppressed generation of action potential in a dose-dependent manner and increased the maximal speed of its growth via changing the volt-ampere characteristics of the incoming current channels [49] Involvement of GABAA-ergic system in the realization of RAF of Abs to S100 effects Notes: * -adapted from [73], CPAR -conditioned passive avoidance reflex, EPM -elevated plus maze, LPT -longterm potentiation.…”

“…Thus, ED is a crucial factor in the bilateral relationship between depression, chronic inflammation, and cardiovascular diseases [73].…”