Neurovascular Alterations in Vascular Dementia: Emphasis on Risk Factors

Abstract

Vascular dementia (VaD) constitutes the second most prevalent cause of dementia in the world after Alzheimer’s disease (AD). VaD regroups heterogeneous neurological conditions in which the decline of cognitive functions, including executive functions, is associated with structural and functional alterations in the cerebral vasculature. Among these cerebrovascular disorders, major stroke, and cerebral small vessel disease (cSVD) constitute the major risk factors for VaD. These conditions alter neurovascular functions leading to blood-brain barrier (BBB) deregulation, neurovascular coupling dysfunction, and inflammation. Accumulation of neurovascular impairments over time underlies the cognitive function decline associated with VaD. Furthermore, several vascular risk factors, such as hypertension, obesity, and diabetes have been shown to exacerbate neurovascular impairments and thus increase VaD prevalence. Importantly, air pollution constitutes an underestimated risk factor that triggers vascular dysfunction via inflammation and oxidative stress. The review summarizes the current knowledge related to the pathological mechanisms linking neurovascular impairments associated with stroke, cSVD, and vascular risk factors with a particular emphasis on air pollution, to VaD etiology and progression. Furthermore, the review discusses the major challenges to fully elucidate the pathobiology of VaD, as well as research directions to outline new therapeutic interventions.

Multifocal Cerebral Microinfarcts Modulate Early Alzheimer’s Disease Pathology in a Sex-Dependent Manner

“…Major efforts have been invested in the past decade to understand the role of vascular risk factors in AD etiology, pathogenesis and progression (9)(10)(11). The overwhelming observations clearly outlined an increased risk of cerebral microinfarct incidence associated with vascular pathologies in AD patients (26)(27)(28)(29)(30).…”

“…The neuropathology of AD is characterized by the deposition of amyloid-b (Ab) plaques associated to Ab accumulation, and the formation of neurofibrillary tangles (NFTs) associated to tau hyperphosphorylation, leading to brain atrophy caused by the loss of neurons and synapses (5)(6)(7)(8). Deregulation of the innate immune response as well as the cerebrovascular functions are now well recognized as main components of AD etiology, pathogenesis and progression (9)(10)(11).…”

Chinese Medicine, Succinum, Ameliorates Cognitive Impairment of Carotid Artery Ligation Rats and Inhibits Apoptosis of HT22 Hippocampal Cells via Regulation of the GSK3β/β-Catenin Pathway

“…In addition, neuronal damage will further activate microglia and induce pro-inflammatory cytokine release, exacerbating neuronal inflammation and reducing neuronal survival ( Qu et al, 2021 ). Meanwhile, the breakdown of blood–brain barrier leads to the penetration of plasma proteins, neurotoxic compounds, and peripheral immune cells into the brain, which aggravates the damage and eventually causes neurological defects ( Lecordier et al, 2021 ). The GSK3β/β-catenin signaling pathway plays an important role in numerous biological processes including neuronal cell growth and proliferation and is also regarded as an important signaling pathway in the pathological mechanism of VD ( Foulquier et al, 2018 ).…”

Air pollution and mental health: associations, mechanisms and methods

“…Following many previous syntheses on the topic, the most recent [51] continues to demonstrate an increased risk of cognitive decline particularly from increasing PM2.5, whereas the associations with dementia, and from other pollutants are less consistent. Specific patterns of cognitive profiles associated with the highest exposure to multiple air pollutants, and neuroimaging studies, have shown incongruenties [52 ▪ ,53–55].…”