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The syndrome confers a high risk of cardiovascular mortality. Indeed, metabolic dysfunction has been shown to cause a direct insult to smooth muscle and endothelial components of the vasculature, which leads to vascular dysfunction and hyperreactivity. This, in turn, causes cerebral vasoconstriction and hypoperfusion, eventually contributing to cognitive deficits. Moreover, the metabolic syndrome disrupts key homeostatic processes in the brain, including apoptosis, autophagy, and neurogenesis. Impairment of such processes in the context of metabolic dysfunction has been implicated in the pathogenesis of neurodegenerative diseases, including Alzheimer, Parkinson, and Huntington diseases.<\/jats:p><jats:p>The aim of this review is to elucidate the role that the metabolic syndrome plays in the pathogenesis of the latter disorders, with a focus on the role of perivascular adipose inflammation in the peripheral\u2010to\u2010central transduction of the inflammatory insult. This review delineates common signaling pathways that contribute to these pathologies. 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