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Many metabolic changes can be grouped into metabolic syndrome (MetS), which is defined as the presence of three or more risk factors, including insulin resistance, hyperglycemia, hypertension, central obesity, and dyslipidemia. These changes cause systemic effects that are crucial in triggering neuroinflammation and neurodegeneration, key factors in AD development. All these factors impair energy metabolism in peripheral tissues and the brain by decreasing glucose utilization, leading to alterations in O-GlcNAcylation, glycosylation, mitochondrial function, oxidative stress, chronic inflammation, synaptic dysfunction, autophagy impairment, and blood\u2013brain barrier (BBB) dysfunction. However, these factors are modified and largely influenced by lifestyle choices. A newer perspective emphasizes that regular exercise is vital for maintaining brain metabolism as we age. Current evidence suggests that engaging in physical activity for individuals with metabolic syndrome reduces their risk of Alzheimer\u2019s disease, enhances prognosis, and improves cognitive abilities. This review explores how metabolic syndrome relates to Alzheimer\u2019s and highlights possible strategies for prevention and treatment.<\/jats:p>","DOI":"10.3390\/brainsci16050465","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T15:09:33Z","timestamp":1777388973000},"page":"465","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Effect of Metabolic Syndrome on Alzheimer\u2019s Disease: Physical Activity as a Preventive and Therapeutic Measure"],"prefix":"10.3390","volume":"16","author":[{"given":"Eleazar","family":"Ram\u00edrez Hern\u00e1ndez","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 04510, 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