Linking Metabolic Syndrome to Neurodegeneration Mechanisms and Potential Treatments.

Abstract

The global rise in both metabolic syndrome (MetS) and neurodegenerative diseases (NDs), particularly dementia and Alzheimer's disease (AD) poses a growing health and socioeconomic burden. MetS affects approximately 25% of the global adult population and is associated with insulin resistance, hypertension, dyslipidemia, and obesity, factors increasingly linked to cognitive impairment and brain atrophy. This review explores the shared pathophysiological mechanisms between MetS and NDs, including neuroinflammation, oxidative stress, insulin resistance in the brain, blood-brain barrier (BBB) dysfunction, mitochondrial damage, gut microbiota dysbiosis, and alterations in the renin-angiotensin system. In terms of substance, MetS patients are four times more likely to develop dementia, with increased markers such as CRP and IL-6 present in the patient populations. The review suggests the role of astrocytic insulin signalling, adipokines, and toll-like receptors as key molecular links. Interventions such as caloric restriction, hydroxytyrosol (HT), and intranasal insulin have shown promising outcomes at preclinical and early clinical stages. Antidiabetic drugs like metformin, liraglutide, and GLP-1 receptor agonists have the potential to modulate neuroinflammation and improve cognition. Angiotensin receptor blockers like losartan and candesartan also exhibit neuroprotection via RAS pathway modulation. The review emphasizes the need for longitudinal studies and clinical trials to confirm these therapeutic agents and develop effective and cost-friendly interventions for the prevention and management of neurodegeneration in patients with metabolic syndrome.