Metals and Cognitive Decline: Pathophysiology, Treatment, and Prevention

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About this Research Topic

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Background

Metals are essential for many biochemical reactions, including energy production and degradation of neurotransmitters, but they can also interact with biomolecules, namely proteins, to induce brain diseases. Although they are essential for normal brain function, their dyshomeostasis (described as a change in their amount, distribution, or activity) can lead to dysfunctional and pathological changes in the brain – resulting in cognitive decline. In this regard, redox-active metal ions were first reported as playing a role, due to their production of reactive oxygen species causing neuronal death. Following this, it has been found that metal dyshomeostasis can also cause neuronal death by disrupting mitochondrial function, or by increasing intracellular free calcium. The interactions of metals with some proteins and some types of cells have been also reported to induce pathological changes including epigenetic events, formation of pathological structures, and inflammatory processes.

The present literature shows that there is a definite relationship between dyshomeostasis of some metals and cognitive decline in aging and in brain diseases, as their levels and distribution change in the brain. However, the details of this relationship are still unclear. In addition to the determination of involved metals and their distribution, metabolism, kinetics; the interactions of metals at molecular and cellular levels, and the factors affecting their metabolism, transportation, and deposition, should be clarified using molecular bioimaging techniques. This can lead to a better understanding of pathophysiology of cognitive decline in aging and in neurodegenerative diseases. Some clinical trials have been performed with supplementation, chelation, or the modulation of metals, which showed positive results on patients with cognitive symptoms. These results were either seen as clinical improvement and/or diminished pathology in the brain. Nevertheless, these drugs also have severe side effects.

The final aim of this Research Topic will be to understand to what extent our findings could be beneficial to the treatment, prevention, and diagnosis of cognitive decline and cognitive disorders. This Research Topic aims to capture new knowledge in both translational and clinical areas, to understand the role of metals in cognition and cognitive disorders, and to find effective measures for the treatment or prevention of cognitive decline.
For this aim, original research manuscripts and/or case reports presenting new findings about the themes below are kindly welcome:

• The levels of metals and/or their distribution in the brain.
• The metabolism, transport and deposition of metals in the brain in relation to cognitive decline and cognitive disorders.
• The factors like environmental, nutritional and/or genetic factors, aging and drug interactions causing metal dyshomeostasis and cognitive decline.
• Treatment trials and options against metal dyshomeostasis and cognitive decline.
• Analytical methods and analysis of samples in the field of metal dyshomeostasis in relation to cognitive decline.
• Prevention measures against metal dyshomeostasis in relation to cognitive decline.

Keywords: Metal dyshomeostasis, cognition, molecular pathology, analysis, treatment

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