Heart and Brain: Complex Relationships for Left Ventricular Dysfunction

Abstract

Purpose of Review This review summarizes the evidence for the established vascular/hypoperfusion model and explores the new hypothesis that configures the heart/brain axis as an organ system where similar pathogenic mechanisms exploit physiological and pathological changes. Recent Findings Although associated by common risk factors, similar epidemiological stratification and common triggers (including inflammation, oxidative stress, and hypoxia), heart failure and Alzheimer's disease have been, for long time, viewed as pathogenically separate illnesses. The silos began to be broken down with the awareness that vascular dysfunction, and loss of cardiac perfusion pump power, trigger biochemical changes, contributing to the typical hallmark of Alzheimer's disease (AD)the accumulation of Aβ plaques and hyperphosphorylated Tau tangles. Compromised blood flow to the brain becomes the paradigm for the "heart-to-head" connection. Compelling evidence of common genetic variants, biochemical characteristics, and the accumulation of Aβ outside the brain suggests a common pathogenesis for heart failure (HF) and AD. These new findings represent just the beginning of the understanding the complex connection between AD and HF requiring further studies and interdisciplinary approaches. Summary Altogether, the current evidence briefly summarized in this review, highlight a closer and complex relationship between heart failure and Alzheimer's that goes beyond the vascular/perfusion hypothesis. Genetic and biochemical evidence begin to suggest common pathogenic mechanisms between the two diseases involving a systemic defect in the folding of protein or a seeding at distance of the misfolded proteins from one organ to the other.

Cognitive Dysfunction after Heart Disease: A Manifestation of the Heart‐Brain Axis

“…Abnormal function of the BBB, including activated endothelial cells, destroyed pericytes, and abnormal endothelial-endothelial and endothelial-pericyte connections, occupies an important position in the pathogenesis of cognitive dysfunction after heart disease [ 35 ]. Inflammation and ROS are thought to be involved in these changes, since the generation of ROS destroys the ion gradient [ 88 ]. Endothelial cells, the main component of the BBB, have been shown to be damaged by an increase in intracellular calcium ion levels [ 89 ].…”

“…The cycle was further exacerbated by the inflammatory response and oxidative stress causing vasoconstriction and promoting destruction of the BBB. A β accumulation in the brain also reportedly has a profound effect on blood vessels, thereby promoting neurodegenerative processes [ 88 ].…”

“…In summary, under the condition of chronic hypoperfusion, damage to the drainage system and decreased ability of glial cells to clear A β lead to the accumulation of A β , eventually causing cognitive impairment. Interestingly, HF with preserved ejection fraction can promote cognitive dysfunction in AD and vice versa [ 88 ]. Overall, HF and cognitive dysfunction are interrelated, and their common pathogenesis may be systemic [ 125 ].…”

“…Amyloid-β Deposition. Although HF and cognitive dysfunction in patients with AD have long been considered independent factors, an increasing number of studies have confirmed that they may be related, with similarities such as common risk factors and similar epidemiological stratification [88]. Moreover, AD-related neuropathology was reported in a rat model after acute blood perfusion ceased, including Aβ deposition in the hippocampus, endothelium, and neocerebral cortex, which led to neuronal death [116].…”

Editorial: Medicinal Plants for Cardiovascular and Neurodegenerative Aging-Related Diseases: From Bench to Bedside

“…Aging presents profound physiological changes in the cardiovascular system and the relationship between cardiovascular pathology and neurodegenerative diseases is well known (Luo et al, 2020). Ischemic events due to cardiac pathology or stroke can lead to cardiovascular dementia and the development of Alzheimer's disease (Daniele et al, 2020). Cardiac pathology has also been found to be associated with other neurodegenerative conditions such as Huntington's disease (Critchley et al, 2018).…”