No abstract

China bears a heavy burden of AD costs, which greatly change the estimates of AD cost worldwide.

Iron is an essential transition metal for numerous biologic processes in mammals. Iron metabolism is regulated via several coordination mechanisms including absorption, utilization, recycling, and storage. Iron dyshomeostasis can result in intracellular iron retention, thereby damaging cells, tissues, and organs through free oxygen radical generation. Numerous studies have shown that brain iron overload is involved in the pathological mechanism of neurodegenerative disease including Alzheimer's disease (AD). However, the underlying mechanisms have not been fully elucidated. Ferroptosis, a newly defined iron-dependent form of cell death, which is distinct from apoptosis, necrosis, autophagy, and other forms of cell death, may provide us a new viewpoint. Here, we set out to summarize the current knowledge of iron metabolism and ferroptosis, and review the contributions of iron and ferroptosis to AD.

Alzheimer's disease (AD) and vascular dementia (VaD) are the most frequent causes of cognitive impairment in the elderly. In the pathogenesis of cognitive impairment, the association of neurodegenerative and vascular factors indicates a major role of hemodynamic abnormalities including cerebral hypoperfusion. There is also ample evidence that oxidative stress of vascular origin leads to profound alterations in cerebrovascular regulation and is crucial to cerebrovascular dysfunction in a variety of conditions that result in chronic hypoperfusion of the brain. In rodents, experimental chronic cerebral hypoperfusion (CCH) can be initiated by occlusion of the major arterial supply. This way CCH brings about mitochondrial dysfunction and protein synthesis inhibition. These effects may destroy the balance of antioxidases and reactive oxygen species (ROS) and produce oxidative damage. At the same time, oxidative injury to vascular endothelial cell, glia, and neuron impairs vascular function and neurovascular coupling, which may result in a vicious cycle of further reduction of cerebral perfusion. In clinical cases of severe cognitive dysfunction, vascular risk factors are commonly present, while cerebral hypoperfusion is often associated with vascular oxidative damage. Thus we hypothesize that cerebral hypoperfusion is one of the key factors in the development of cognitive impairment, in which vascular oxidative stress plays a major role. The approaches against cerebrovascular dysfunction, combined with antioxidants and others, might make a promising contribution to the treatment of cognitive impairment.

Over the 6-month treatment period, NBP was effective for improving cognitive and global functioning in patients with subcortical vascular cognitive impairment without dementia and exhibited good safety.