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Mini Review
24 August 2022

This review highlights that depression is a growing health problem for the individual, and because of its high frequency in most societies, a growing burden on health care budgets. The focus of the review is the physiological links between depression and dementia, specifically Alzheimer’s disease. It suggests that depression is a significant risk factor for cognitive decline and explores the pathways that may lead depressed individuals to suffer this outcome. This review shows that depression and a number of its precursors activate pro-inflammatory mediators. These lead to cerebral small vessel disease with the consequent reduction in cerebral blood flow, which is known to precede cognitive decline. Thus, the impact of depression on the physiological events that lead to dementia is identical to the impact of other dementia risk factors recently reviewed. Depression is distinct, however, in being a relatively treatable condition, but the impact of treating depression on later cognitive decline is not always positive, leading to the hypothesis that only the antidepressants that attenuate inflammation alleviate subsequent cognitive decline.

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The vagus nerve is the longest nerve in the human body, providing afferent information about visceral sensation, integrity and somatic sensations to the CNS via brainstem nuclei to subcortical and cortical structures. Its efferent arm influences GI motility and secretion, cardiac ionotropy, chonotropy and heart rate variability, blood pressure responses, bronchoconstriction and modulates gag and cough responses via palatine and pharyngeal innervation. Vagus nerve stimulation has been utilized as a successful treatment for intractable epilepsy and treatment-resistant depression, and new non-invasive transcutaneous (t-VNS) devices offer equivalent therapeutic potential as invasive devices without the surgical risks. t-VNS offers exciting potential as a therapeutic intervention in cognitive decline and aging populations, classically affected by reduced cerebral perfusion by modulating both limbic and frontal cortical structures, regulating cerebral perfusion and improving parasympathetic modulation of the cardiovascular system. In this narrative review we summarize the research to date investigating the cognitive effects of VNS therapy, and its effects on neurocardiovascular stability.

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Frontiers in Molecular Biosciences

Estrogens and Neurodegeneration: a Link Between Menopause and Alzheimer’s Diseases in Women
Edited by Manuela Leri, Andrea Bertolini, Roberta Marongiu, Mario Diaz
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28 April 2025
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