The Effect of Metabolic Syndrome on Alzheimer’s Disease: Physical Activity as a Preventative and Therapeutic Measure

Epidemiological and clinical research on neurodegenerative diseases have indicated that metabolic dysregulations increase the risk of developing Alzheimer's Disease (AD). Many metabolic alterations can be grouped within the metabolic syndrome (MetS), defined as the coexistence of three or more risk factors, such as insulin resistance, hyperglycemia, hypertension, central obesity, and dyslipidemia. These changes induce a systemic change that plays a critical role in inducing neuroinflammation and neurodegeneration as essential causes of AD pathogenesis. All these factors compromise peripheral tissues and brain energy metabolism through reduced glucose utilization, which contributes to alterations in O-GlcNAcylation, glycosylation, mitochondrial dysfunction, oxidative stress, chronic inflammation, synaptic dysfunction, impaired autophagy, and blood-brain barrier (BBB) dysfunction. However, these factors are modifiable elements that depend on lifestyle. A relatively new perspective proposes that exercise regularly plays an essential role in maintaining brain metabolism in ageing. Physical activity in MetS decreases the risk of developing Alzheimer's disease, is associated with better prognosis, and positively affects cognitive function in those patients. In this review, we discuss the mechanisms involved in MetS and their implication in AD and identify potential areas for preventive and therapeutic interventions.