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The interplay between these interventions highlights their potential to enhance cognitive function by promoting neurogenesis, synaptic plasticity, and resilience against oxidative stress and inflammation. Mechanistic insights reveal that exercise and polyphenols activate complementary neuroprotective pathways, including the upregulation of BDNF and CREB, as well as the modulation of antioxidant defenses via Nrf2. Evidence from both animal and human studies demonstrates significant improvements in spatial memory and hippocampal function when these strategies are combined. Despite promising findings, challenges related to bioavailability, dosing, and long\u2010term efficacy remain, underscoring the need for further investigation. This review emphasizes the potential clinical applications of these combined approaches for preventing cognitive decline and promoting brain health during aging and in neurodegenerative conditions.<\/jats:p>","DOI":"10.1002\/ptr.70341","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T11:00:37Z","timestamp":1776682837000},"page":"3909-3935","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Synergistic Effects of Exercise and Dietary Polyphenols on Cognitive Function and Neuroprotection in Aging: A Focus on Spatial Learning and Memory"],"prefix":"10.1002","volume":"40","author":[{"given":"Rui","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University  Xiamen China"},{"name":"Provincial Key Cultivation Laboratory of Intelligent Big Data Digital Neurosurgery of Shanxi Province  Taiyuan Shanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejing","family":"Yang","sequence":"additional","affiliation":[{"name":"Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University  Taiyuan China"},{"name":"Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyang","family":"Su","sequence":"additional","affiliation":[{"name":"Provincial Key Cultivation Laboratory of Intelligent Big Data Digital Neurosurgery of Shanxi Province  Taiyuan Shanxi China"},{"name":"Shanxi Provincial People's Hospital  Taiyuan Shanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyu","family":"Wei","sequence":"additional","affiliation":[{"name":"Provincial Key Cultivation Laboratory of Intelligent Big Data Digital Neurosurgery of Shanxi Province  Taiyuan Shanxi China"},{"name":"Shanxi Provincial People's Hospital  Taiyuan Shanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1273-6832","authenticated-orcid":false,"given":"Hongming","family":"Ji","sequence":"additional","affiliation":[{"name":"Provincial Key Cultivation Laboratory of Intelligent Big Data Digital Neurosurgery of Shanxi Province  Taiyuan Shanxi China"},{"name":"Shanxi Provincial People's Hospital  Taiyuan Shanxi China"},{"name":"The Fifth Clinical Medical College of Shanxi Medical University  Taiyuan Shanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0833-4728","authenticated-orcid":false,"given":"Dong","family":"Song","sequence":"additional","affiliation":[{"name":"Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University  Taiyuan China"},{"name":"Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"e_1_2_16_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2017.11.012"},{"key":"e_1_2_16_3_1","first-page":"147","volume-title":"Studies in Natural Products Chemistry","author":"Ac\u0131kara \u00d6. 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