{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:48:14Z","timestamp":1793317694411,"version":"4.5.0"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:00:00Z","timestamp":1748476800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:00:00Z","timestamp":1748476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK129320"],"award-info":[{"award-number":["R01DK129320"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK129320"],"award-info":[{"award-number":["R01DK129320"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK129320"],"award-info":[{"award-number":["R01DK129320"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1137837"],"award-info":[{"award-number":["1137837"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Low physical activity (PA) and obesity are dementia risk factors, but it is unclear whether the association between PA and brain health is dependent upon degree of obesity. We aimed to examine the association between PA and brain structure and explore whether it varies by body mass index (BMI). We examined the associations between accelerometer-measured PA and magnetic resonance imaging-measured brain structure using cross-sectional data from a population-based cohort of people in midlife (UK Biobank). Using regression modelling, we explored whether these associations were mediated by BMI or other cardiometabolic risk factors. Complete data were available for 16,725 participants (median age 65\u00a0years, 55% women, median BMI 26). Greater PA was positively associated with total brain (\u03b2\u2009=\u20093.67,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001), grey matter (\u03b2\u2009=\u20093.12,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001), white matter (\u03b2\u2009=\u20090.43,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001) and total hippocampal volumes (\u03b2\u2009=\u20090.05,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001), and inversely associated with white matter hyperintensity volume (\u03b2\u2009=\u2009\u2212\u20094.6\u2009\u00d7\u200910\n                    <jats:sup>\u22125<\/jats:sup>\n                    ,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001). Although there was no interaction between PA and BMI in explaining brain volumes, BMI attenuated the PA-brain volume associations by between 18 and 58%. The PA-brain volume associations were further attenuated by other cardiometabolic risk factors and in the case of grey matter and hippocampal volume, was no longer statistically significant in fully adjusted models. Greater PA is associated with a healthier profile in brain volumes. BMI and cardiometabolic factors mediated the relationship between PA and grey matter and hippocampal volume and partially mediated its relationship with other brain volumes. These results support a mechanistic basis for PA in optimizing cardiometabolic risk for dementia prevention.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-04010-7","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T09:08:55Z","timestamp":1748509735000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Associations between physical activity and brain structure in a large community cohort"],"prefix":"10.1038","volume":"15","author":[{"given":"Alexandra","family":"La Hood","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Moran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Than","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taya A.","family":"Collyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Beare","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Velandai","family":"Srikanth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,29]]},"reference":[{"key":"4010_CR1","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1017\/S0033291708003681","volume":"39","author":"M Hamer","year":"2009","unstructured":"Hamer, M. & Chida, Y. Physical activity and risk of neurodegenerative disease: A systematic review of prospective evidence. Psychol. Med. 39, 3\u201311. https:\/\/doi.org\/10.1017\/S0033291708003681 (2009).","journal-title":"Psychol. Med."},{"key":"4010_CR2","doi-asserted-by":"publisher","first-page":"3041","DOI":"10.1002\/alz.12908","volume":"19","author":"S Nguyen","year":"2022","unstructured":"Nguyen, S. et al. Accelerometer-measured physical activity and sitting with incident mild cognitive impairment or probable dementia among older women. Alzheimers Dement. 19, 3041\u20133054. https:\/\/doi.org\/10.1002\/alz.12908 (2022).","journal-title":"Alzheimers Dement."},{"key":"4010_CR3","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s12966-023-01464-8","volume":"20","author":"Q Zhong","year":"2023","unstructured":"Zhong, Q. et al. The independent and joint association of accelerometer-measured physical activity and sedentary time with dementia: A cohort study in the UK Biobank. Int. J. Behav. Nutr. Phys. Act. 20, 59. https:\/\/doi.org\/10.1186\/s12966-023-01464-8 (2023).","journal-title":"Int. J. Behav. Nutr. Phys. Act."},{"key":"4010_CR4","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1001\/jamaneurol.2022.2672","volume":"79","author":"B Del Pozo Cruz","year":"2022","unstructured":"Del Pozo Cruz, B., Ahmadi, M., Naismith, S. L. & Stamatakis, E. Association of daily step count and intensity with incident dementia in 78 430 adults living in the UK. JAMA Neurol. 79, 1059\u20131063. https:\/\/doi.org\/10.1001\/jamaneurol.2022.2672 (2022).","journal-title":"JAMA Neurol."},{"key":"4010_CR5","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1177\/0271678X20957807","volume":"41","author":"ES Bliss","year":"2021","unstructured":"Bliss, E. S., Wong, R. H., Howe, P. R. & Mills, D. E. Benefits of exercise training on cerebrovascular and cognitive function in ageing. J. Cereb. Blood Flow Metab. 41, 447\u2013470. https:\/\/doi.org\/10.1177\/0271678X20957807 (2021).","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"4010_CR6","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.neurobiolaging.2019.03.007","volume":"79","author":"RS Falck","year":"2019","unstructured":"Falck, R. S., Davis, J. C., Best, J. R., Crockett, R. A. & Liu-Ambrose, T. Impact of exercise training on physical and cognitive function among older adults: A systematic review and meta-analysis. Neurobiol. Aging 79, 119\u2013130. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2019.03.007 (2019).","journal-title":"Neurobiol. Aging"},{"key":"4010_CR7","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1101\/2022.01.01.22268616","volume":"88","author":"BM Brown","year":"2022","unstructured":"Brown, B. M. et al. Non-modifiable factors as moderators of the relationship between physical activity and brain volume: A cross-sectional UK Biobank study. J. Alzheimers Dis. 88, 1091\u20131101. https:\/\/doi.org\/10.1101\/2022.01.01.22268616 (2022).","journal-title":"J. Alzheimers Dis."},{"key":"4010_CR8","doi-asserted-by":"publisher","first-page":"e1202","DOI":"10.1212\/WNL.0000000000200884","volume":"99","author":"FAU Fox","year":"2022","unstructured":"Fox, F. A. U. et al. Association between accelerometer-derived physical activity measurements and brain structure: A population-based cohort study. Neurology 99, e1202\u2013e1215. https:\/\/doi.org\/10.1212\/WNL.0000000000200884 (2022).","journal-title":"Neurology"},{"key":"4010_CR9","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1111\/joim.12772","volume":"284","author":"M Hamer","year":"2018","unstructured":"Hamer, M., Sharma, N. & Batty, G. D. Association of objectively measured physical activity with brain structure: UK Biobank study. J. Intern. Med. 284, 439\u2013443. https:\/\/doi.org\/10.1111\/joim.12772 (2018).","journal-title":"J. Intern. Med."},{"key":"4010_CR10","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1093\/geronb\/gby010","volume":"74","author":"S Halloway","year":"2019","unstructured":"Halloway, S., Arfanakis, K., Wilbur, J., Schoeny, M. E. & Pressler, S. J. Accelerometer physical activity is associated with greater gray matter volumes in older adults without dementia or mild cognitive impairment. J. Gerontol. Ser. B 74, 1142\u20131151. https:\/\/doi.org\/10.1093\/geronb\/gby010 (2019).","journal-title":"J. Gerontol. Ser. B"},{"key":"4010_CR11","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.neuroscience.2014.05.005","volume":"273","author":"MN Braskie","year":"2014","unstructured":"Braskie, M. N. et al. Physical activity, inflammation, and volume of the aging brain. Neuroscience 273, 199\u2013209. https:\/\/doi.org\/10.1016\/j.neuroscience.2014.05.005 (2014).","journal-title":"Neuroscience"},{"key":"4010_CR12","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2020.26506","volume":"3","author":"Y Gu","year":"2020","unstructured":"Gu, Y. et al. Assessment of leisure time physical activity and brain health in a multiethnic cohort of older adults. JAMA Netw. Open 3, e2026506. https:\/\/doi.org\/10.1001\/jamanetworkopen.2020.26506 (2020).","journal-title":"JAMA Netw. Open"},{"key":"4010_CR13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0253484","volume":"16","author":"RJ Dawe","year":"2021","unstructured":"Dawe, R. J. et al. Physical activity, brain tissue microstructure, and cognition in older adults. PLoS ONE 16, e0253484. https:\/\/doi.org\/10.1371\/journal.pone.0253484 (2021).","journal-title":"PLoS ONE"},{"key":"4010_CR14","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2021.102767","volume":"31","author":"AM Sanders","year":"2021","unstructured":"Sanders, A. M. et al. Linking objective measures of physical activity and capability with brain structure in healthy community dwelling older adults. Neuroimage Clin. 31, 102767. https:\/\/doi.org\/10.1016\/j.nicl.2021.102767 (2021).","journal-title":"Neuroimage Clin."},{"key":"4010_CR15","doi-asserted-by":"publisher","first-page":"1504","DOI":"10.1093\/gerona\/glaa294","volume":"76","author":"AA Wanigatunga","year":"2021","unstructured":"Wanigatunga, A. A. et al. Association between brain volumes and patterns of physical activity in community-dwelling older adults. J. Gerontol. A Biol. Sci. Med. Sci. 76, 1504\u20131511. https:\/\/doi.org\/10.1093\/gerona\/glaa294 (2021).","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"4010_CR16","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1097\/PSY.0000000000000212","volume":"77","author":"GN Bischof","year":"2015","unstructured":"Bischof, G. N. & Park, D. C. Obesity and aging: Consequences for cognition, brain structure, and brain function. Psychosom. Med. 77, 697\u2013709. https:\/\/doi.org\/10.1097\/PSY.0000000000000212 (2015).","journal-title":"Psychosom. Med."},{"key":"4010_CR17","doi-asserted-by":"publisher","first-page":"97","DOI":"10.3389\/fnagi.2013.00097","volume":"5","author":"JS Chan","year":"2013","unstructured":"Chan, J. S., Yan, J. H. & Payne, V. G. The impact of obesity and exercise on cognitive aging. Front. Aging Neurosci. 5, 97. https:\/\/doi.org\/10.3389\/fnagi.2013.00097 (2013).","journal-title":"Front. Aging Neurosci."},{"key":"4010_CR18","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1007\/s40279-020-01292-x","volume":"50","author":"FT Chen","year":"2020","unstructured":"Chen, F. T. et al. Effects of exercise training interventions on executive function in older adults: A systematic review and meta-analysis. Sports Med. 50, 1451\u20131467. https:\/\/doi.org\/10.1007\/s40279-020-01292-x (2020).","journal-title":"Sports Med."},{"key":"4010_CR19","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1007\/s00429-021-02247-2","volume":"226","author":"Q Yu","year":"2021","unstructured":"Yu, Q. et al. Cognitive benefits of exercise interventions: An fMRI activation likelihood estimation meta-analysis. Brain Struct. Funct. 226, 601\u2013619. https:\/\/doi.org\/10.1007\/s00429-021-02247-2 (2021).","journal-title":"Brain Struct. Funct."},{"key":"4010_CR20","doi-asserted-by":"publisher","first-page":"e2023","DOI":"10.1212\/WNL.0000000000200270","volume":"98","author":"F Felisatti","year":"2022","unstructured":"Felisatti, F. et al. Role of cardiovascular risk factors on the association between physical activity and brain integrity markers in older adults. Neurology 98, e2023\u2013e2035 (2022).","journal-title":"Neurology"},{"key":"4010_CR21","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1016\/j.jsams.2022.05.009","volume":"25","author":"JL Tait","year":"2022","unstructured":"Tait, J. L. et al. Longitudinal associations of childhood fitness and obesity profiles with midlife cognitive function: An Australian cohort study. J. Sci. Med. Sport 25, 667\u2013672. https:\/\/doi.org\/10.1016\/j.jsams.2022.05.009 (2022).","journal-title":"J. Sci. Med. Sport"},{"key":"4010_CR22","unstructured":"Prince M., et al. World Alzheimer Report (2015)."},{"key":"4010_CR23","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/S0140-6736(20)30367-6","volume":"396","author":"G Livingston","year":"2020","unstructured":"Livingston, G. et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet 396, 413\u2013446. https:\/\/doi.org\/10.1016\/S0140-6736(20)30367-6 (2020).","journal-title":"Lancet"},{"key":"4010_CR24","volume-title":"Risk Reduction of Cognitive Decline and Dementia: WHO Guidelines","author":"World Health Organisation","year":"2019","unstructured":"World Health Organisation. Risk Reduction of Cognitive Decline and Dementia: WHO Guidelines (World Health Organisation, 2019)."},{"key":"4010_CR25","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/nrneurol.2017.96","volume":"13","author":"FM Elahi","year":"2017","unstructured":"Elahi, F. M. & Miller, B. L. A clinicopathological approach to the diagnosis of dementia. Nat. Rev. Neurol. 13, 457\u2013476. https:\/\/doi.org\/10.1038\/nrneurol.2017.96 (2017).","journal-title":"Nat. Rev. Neurol."},{"key":"4010_CR26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001779","volume":"12","author":"C Sudlow","year":"2015","unstructured":"Sudlow, C. et al. UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med. 12, e1001779. https:\/\/doi.org\/10.1371\/journal.pmed.1001779 (2015).","journal-title":"PLoS Med."},{"key":"4010_CR27","doi-asserted-by":"publisher","DOI":"10.4324\/9781003368885","volume-title":"Health and Deprivation: Inequality and the North","author":"P Townsend","year":"2023","unstructured":"Townsend, P., Phillimore, P. & Beattie, A. Health and Deprivation: Inequality and the North Vol. 8 (Taylor & Francis, 2023)."},{"key":"4010_CR28","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1210\/clinem\/dgaa847","volume":"106","author":"S Than","year":"2021","unstructured":"Than, S. et al. Interactions between age, sex, menopause, and brain structure at midlife: A UK biobank study. J. Clin. Endocrinol. Metab. 106, 410\u2013420. https:\/\/doi.org\/10.1210\/clinem\/dgaa847 (2021).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"4010_CR29","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.1249\/01.Mss.0000078924.61453.Fb","volume":"35","author":"CL Craig","year":"2003","unstructured":"Craig, C. L. et al. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 35, 1381\u20131395. https:\/\/doi.org\/10.1249\/01.Mss.0000078924.61453.Fb (2003).","journal-title":"Med Sci Sports Exerc."},{"key":"4010_CR30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1479-5868-6-21","volume":"6","author":"A Bauman","year":"2009","unstructured":"Bauman, A. et al. The international prevalence study on physical activity: Results from 20 countries. Int. J. Behav. Nutr. Phys. Act. 6, 1\u201311 (2009).","journal-title":"Int. J. Behav. Nutr. Phys. Act."},{"key":"4010_CR31","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/j.neuroimage.2017.10.034","volume":"166","author":"F Alfaro-Almagro","year":"2018","unstructured":"Alfaro-Almagro, F. et al. Image processing and quality control for the first 10,000 brain imaging datasets from UK Biobank. Neuroimage 166, 400\u2013424. https:\/\/doi.org\/10.1016\/j.neuroimage.2017.10.034 (2018).","journal-title":"Neuroimage"},{"key":"4010_CR32","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1006\/nimg.2002.1040","volume":"17","author":"SM Smith","year":"2002","unstructured":"Smith, S. M. et al. Accurate, robust, and automated longitudinal and cross-sectional brain change analysis. Neuroimage 17, 479\u2013489. https:\/\/doi.org\/10.1006\/nimg.2002.1040 (2002).","journal-title":"Neuroimage"},{"key":"4010_CR33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0169649","volume":"12","author":"A Doherty","year":"2017","unstructured":"Doherty, A. et al. Large scale population assessment of physical activity using wrist worn accelerometers: The UK biobank study. PLoS ONE 12, e0169649. https:\/\/doi.org\/10.1371\/journal.pone.0169649 (2017).","journal-title":"PLoS ONE"},{"key":"4010_CR34","doi-asserted-by":"publisher","DOI":"10.1093\/geronb\/gbaf071","author":"S Maltagliati","year":"2025","unstructured":"Maltagliati, S. et al. Non-linear associations of accelerometer-based sedentary time with cognitive functions in the UK Biobank. J. Gerontol. Ser. B Psychol. Sci. Soc. Sci. https:\/\/doi.org\/10.1093\/geronb\/gbaf071 (2025).","journal-title":"J. Gerontol. Ser. B Psychol. Sci. Soc. Sci."},{"key":"4010_CR35","unstructured":"World Health Organisation. Obesity: Preventing and Managing the Global Epidemic. Report of a WHO Consultation, vol. 894, i\u2013xii, 1\u2013253. World Health Organ Tech Rep Ser. 0512-3054 (Print) 0512-3054 (2000)."},{"key":"4010_CR36","doi-asserted-by":"publisher","first-page":"1816","DOI":"10.1249\/MSS.0000000000000289","volume":"46","author":"M Hildebrand","year":"2014","unstructured":"Hildebrand, M., Van Hees, V. T., Hansen, B. H. & Ekelund, U. Age group comparability of raw accelerometer output from wrist-and hip-worn monitors. Med. Sci. Sports Exerc. 46, 1816\u20131824 (2014).","journal-title":"Med. Sci. Sports Exerc."},{"key":"4010_CR37","doi-asserted-by":"publisher","first-page":"1814","DOI":"10.1111\/sms.12795","volume":"27","author":"M Hildebrand","year":"2017","unstructured":"Hildebrand, M., Hansen, B. H., van Hees, V. T. & Ekelund, U. Evaluation of raw acceleration sedentary thresholds in children and adults. Scand. J. Med. Sci. Sports 27, 1814\u20131823 (2017).","journal-title":"Scand. J. Med. Sci. Sports"},{"key":"4010_CR38","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.metabol.2018.10.009","volume":"92","author":"A Petridou","year":"2019","unstructured":"Petridou, A., Siopi, A. & Mougios, V. Exercise in the management of obesity. Metabolism 92, 163\u2013169. https:\/\/doi.org\/10.1016\/j.metabol.2018.10.009 (2019).","journal-title":"Metabolism"},{"key":"4010_CR39","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.115.002014","volume":"4","author":"X Lin","year":"2015","unstructured":"Lin, X. et al. Effects of exercise training on cardiorespiratory fitness and biomarkers of cardiometabolic health: A systematic review and meta-analysis of randomized controlled trials. J. Am. Heart. Assoc. 4, e002014. https:\/\/doi.org\/10.1161\/JAHA.115.002014 (2015).","journal-title":"J. Am. Heart. Assoc."},{"key":"4010_CR40","doi-asserted-by":"publisher","first-page":"189","DOI":"10.3945\/ajcn.113.082883","volume":"100","author":"N Napoli","year":"2014","unstructured":"Napoli, N. et al. Effect of weight loss, exercise, or both on cognition and quality of life in obese older adults. Am. J. Clin. Nutr. 100, 189\u2013198. https:\/\/doi.org\/10.3945\/ajcn.113.082883 (2014).","journal-title":"Am. J. Clin. Nutr."},{"key":"4010_CR41","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/0006-8993(96)00273-9","volume":"726","author":"SA Neeper","year":"1996","unstructured":"Neeper, S. A., Gomez-Pinilla, F., Choi, J. & Cotman, C. W. Physical activity increases mRNA for brain-derived neurotrophic factor and nerve growth factor in rat brain. Brain Res. 726, 49\u201356 (1996).","journal-title":"Brain Res."},{"key":"4010_CR42","doi-asserted-by":"publisher","first-page":"1628","DOI":"10.1523\/JNEUROSCI.21-05-01628.2001","volume":"21","author":"JL Trejo","year":"2001","unstructured":"Trejo, J. L., Carro, E. & Torres-Aleman, I. Circulating insulin-like growth factor I mediates exercise-induced increases in the number of new neurons in the adult hippocampus. J. Neurosci. 21, 1628\u20131634. https:\/\/doi.org\/10.1523\/JNEUROSCI.21-05-01628.2001 (2001).","journal-title":"J. Neurosci."},{"key":"4010_CR43","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/230791","volume":"2014","author":"S Viboolvorakul","year":"2014","unstructured":"Viboolvorakul, S. & Patumraj, S. Exercise training could improve age-related changes in cerebral blood flow and capillary vascularity through the upregulation of VEGF and eNOS. Biomed. Res. Int. 2014, 230791. https:\/\/doi.org\/10.1155\/2014\/230791 (2014).","journal-title":"Biomed. Res. Int."},{"key":"4010_CR44","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.761674","volume":"13","author":"H Umegaki","year":"2021","unstructured":"Umegaki, H., Sakurai, T. & Arai, H. Active life for brain health: A narrative review of the mechanism underlying the protective effects of physical activity on the brain. Front. Aging Neurosci. 13, 761674. https:\/\/doi.org\/10.3389\/fnagi.2021.761674 (2021).","journal-title":"Front. Aging Neurosci."},{"key":"4010_CR45","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.981002","volume":"14","author":"B Zhou","year":"2022","unstructured":"Zhou, B. et al. Effects of different physical activities on brain-derived neurotrophic factor: A systematic review and Bayesian network meta-analysis. Systematic review. Front. Aging Neurosci. 14, 981002. https:\/\/doi.org\/10.3389\/fnagi.2022.981002 (2022).","journal-title":"Front. Aging Neurosci."},{"key":"4010_CR46","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1186\/s12986-022-00687-z","volume":"19","author":"X Xue","year":"2022","unstructured":"Xue, X., Liu, B., Hu, J., Bian, X. & Lou, S. The potential mechanisms of lactate in mediating exercise-enhanced cognitive function: A dual role as an energy supply substrate and a signaling molecule. Nutr. Metab. (Lond.) 19, 52. https:\/\/doi.org\/10.1186\/s12986-022-00687-z (2022).","journal-title":"Nutr. Metab. (Lond.)"},{"key":"4010_CR47","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1161\/ATVBAHA.115.306768","volume":"36","author":"FJ Wolters","year":"2016","unstructured":"Wolters, F. J. et al. Cerebral vasoreactivity, apolipoprotein E, and the risk of dementia: A population-based study. Arterioscler. Thromb. Vasc. Biol. 36, 204\u2013210. https:\/\/doi.org\/10.1161\/ATVBAHA.115.306768 (2016).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"4010_CR48","doi-asserted-by":"publisher","first-page":"2583","DOI":"10.1007\/s11064-015-1581-6","volume":"40","author":"NA Jessen","year":"2015","unstructured":"Jessen, N. A., Munk, A. S., Lundgaard, I. & Nedergaard, M. The glymphatic system: A beginner\u2019s guide. Neurochem. Res. 40, 2583\u20132599. https:\/\/doi.org\/10.1007\/s11064-015-1581-6 (2015).","journal-title":"Neurochem. Res."},{"key":"4010_CR49","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1152\/japplphysiol.00164.2004","volume":"98","author":"AM Petersen","year":"2005","unstructured":"Petersen, A. M. & Pedersen, B. K. The anti-inflammatory effect of exercise. J. Appl. Physiol. (1985) 98, 1154\u20131162. https:\/\/doi.org\/10.1152\/japplphysiol.00164.2004 (2005).","journal-title":"J. Appl. Physiol. (1985)"},{"key":"4010_CR50","doi-asserted-by":"publisher","first-page":"1450","DOI":"10.1016\/j.jalz.2018.02.014","volume":"14","author":"SKL Darweesh","year":"2018","unstructured":"Darweesh, S. K. L. et al. Inflammatory markers and the risk of dementia and Alzheimer\u2019s disease: A meta-analysis. Alzheimers Dement. 14, 1450\u20131459. https:\/\/doi.org\/10.1016\/j.jalz.2018.02.014 (2018).","journal-title":"Alzheimers Dement."},{"key":"4010_CR51","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1002\/alz.12237","volume":"17","author":"G Grande","year":"2021","unstructured":"Grande, G. et al. Multimorbidity burden and dementia risk in older adults: The role of inflammation and genetics. Alzheimers Dement. 17, 768\u2013776. https:\/\/doi.org\/10.1002\/alz.12237 (2021).","journal-title":"Alzheimers Dement."},{"key":"4010_CR52","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1093\/epirev\/mxab004","volume":"43","author":"F Liu","year":"2022","unstructured":"Liu, F., Wanigatunga, A. A. & Schrack, J. A. Assessment of physical activity in adults using wrist accelerometers. Epidemiol. Rev. 43, 65\u201393. https:\/\/doi.org\/10.1093\/epirev\/mxab004 (2022).","journal-title":"Epidemiol. Rev."},{"key":"4010_CR53","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1093\/aje\/kwx246","volume":"186","author":"A Fry","year":"2017","unstructured":"Fry, A. et al. Comparison of sociodemographic and health-related characteristics of UK biobank participants with those of the general population. Am. J. Epidemiol. 186, 1026\u20131034. https:\/\/doi.org\/10.1093\/aje\/kwx246 (2017).","journal-title":"Am. J. Epidemiol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-04010-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-04010-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-04010-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T09:08:57Z","timestamp":1748509737000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-04010-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,29]]},"references-count":53,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["4010"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-04010-7","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,29]]},"assertion":[{"value":"14 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 May 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"18896"}}