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Depression has a high incidence in the elderly and is considered a risk factor for the development of dementia, being a promising target for dementia prevention strategies. Additionally, dementia and depression share common mechanisms through which they manifest pathologically. This review addresses the potential shared mechanisms between dementia and depression, including hypothalamic\u2013pituitary\u2013adrenal (HPA) axis dysfunction, brain atrophy (mainly hippocampus and prefrontal cortex), cognitive decline, and neuroinflammation. It also explores the therapeutic potential of physical exercise in modulating these shared pathways, highlighting its role as a non\u2010pharmacological intervention for the treatment and prevention of both disorders. The review also explores the muscle\u2013brain crosstalk and the intracellular pathways through which physical exercise exerts its effects.<\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70185-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70185","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T12:54:39Z","timestamp":1754312079000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Shared Mechanisms in Dementia and Depression: The Modulatory Role of Physical Exercise"],"prefix":"10.1111","volume":"169","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4227-5865","authenticated-orcid":false,"given":"Pedro","family":"Borges de Souza","sequence":"first","affiliation":[{"name":"Center of Biological Sciences, Department of Biochemistry Federal University of Santa Catarina  Florian\u00f3polis SC Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6285-8780","authenticated-orcid":false,"given":"Ana L\u00facia S.","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Center of Biological Sciences, Department of Biochemistry Federal University of Santa Catarina  Florian\u00f3polis SC Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8358-0589","authenticated-orcid":false,"given":"Fernanda G.","family":"De Felice","sequence":"additional","affiliation":[{"name":"Centre for Neuroscience Studies, Department of Biomedical and Molecular Sciences &amp; Department of Psychiatry Queen's University  Kingston Ontario Canada"},{"name":"D'Or Institute for Research and Education  Rio de Janeiro RJ Brazil"},{"name":"Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro  Rio de Janeiro RJ 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