{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:46:22Z","timestamp":1787323582789,"version":"build-2736575974"},"reference-count":50,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Forschung, Technologie und Raumfahrt","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["101041677"],"award-info":[{"award-number":["101041677"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["CSC202108080131"],"award-info":[{"award-number":["CSC202108080131"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010146","name":"Alzheimer Forschung Initiative","doi-asserted-by":"publisher","award":["25081E"],"award-info":[{"award-number":["25081E"]}],"id":[{"id":"10.13039\/100010146","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    White matter integrity is a sensitive marker of cerebrovascular health and aging. Physical activity may promote white matter health, but previous studies were limited by self\u2010reported activity and small sample sizes. We examined the association between accelerometer\u2010based physical activity and novel indices of white matter integrity while identifying potential mediators. We analyzed cross\u2010sectional baseline data from 4188 participants (58% women, mean age: 55.4\u2009years) of the Rhineland Study, a prospective cohort study in Bonn, Germany. Physical activity measures (independent variables) were derived from activPAL3 micro\u2010accelerometers. Fractional anisotropy, mean diffusivity, free water fraction, orientation dispersion, and neurite density (outcomes) were obtained from 3 T MR images for the whole brain and across 27 white matter tracts. We performed multivariable polynomial regression and mediation analyses for cardiometabolic and inflammatory factors. Higher energy expenditure was related to lower orientation dispersion, with the association leveling off at higher amounts (standardized\n                    <jats:italic>\u03b2<\/jats:italic>\n                    <jats:sub>linear<\/jats:sub>\n                    = \u22120.153 [\u22120.183; \u22120.122];\n                    <jats:italic>\u03b2<\/jats:italic>\n                    <jats:sub>quadratic<\/jats:sub>\n                    =\u20090.034 [0.017; 0.051]; both\n                    <jats:italic>p<\/jats:italic>\n                    &lt;\u20090.001). Physical activity was linked to lower neurite density in motor tracts (\n                    <jats:italic>\u03b2<\/jats:italic>\n                    s between \u22120.133 and \u22120.056, all\n                    <jats:italic>p<\/jats:italic>\n                    &lt;\u20090.001). However, with advancing age, physical activity became more strongly associated with higher neurite density and lower mean diffusivity of supratentorial fibers. Body weight, cardiometabolic, and inflammatory factors partly mediated effects of physical activity on white matter microstructure. Physical activity is related to white matter integrity in a nonlinear, age\u2010 and region\u2010specific way. Physical activity's effects are greatest in sedentary and older individuals, likely mediated through its impact on body composition, cardiometabolic health, and systemic inflammation.\n                  <\/jats:p>","DOI":"10.1111\/acel.70659","type":"journal-article","created":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T03:18:34Z","timestamp":1786159114000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Physical Activity on Brain White Matter Integrity Are Region\u2010, Dose\u2010, and Age\u2010Dependent: Findings From the Population\u2010Based Rhineland Study"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8300-3157","authenticated-orcid":false,"given":"Eva","family":"Saxler","sequence":"first","affiliation":[{"name":"Population Health Sciences German Centre for Neurodegenerative Diseases (DZNE)  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabienne A. U.","family":"Fox","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry University of Groningen, University Medical Center Groningen  Groningen the Netherlands"},{"name":"Accare Child Study Center  Groningen the Netherlands"},{"name":"The Research School of Behavioural and Cognitive Neurosciences University of Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9795-0541","authenticated-orcid":false,"given":"Alexandra","family":"Koch","sequence":"additional","affiliation":[{"name":"Population Health Sciences German Centre for Neurodegenerative Diseases (DZNE)  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4071-7950","authenticated-orcid":false,"given":"Xingwang","family":"Yang","sequence":"additional","affiliation":[{"name":"Population Health Sciences German Centre for Neurodegenerative Diseases (DZNE)  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2516-9710","authenticated-orcid":false,"given":"Weiyi","family":"Zeng","sequence":"additional","affiliation":[{"name":"Population Health Sciences German Centre for Neurodegenerative Diseases (DZNE)  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0339-8870","authenticated-orcid":false,"given":"Santiago","family":"Estrada","sequence":"additional","affiliation":[{"name":"Population Health Sciences German Centre for Neurodegenerative Diseases (DZNE)  Bonn Germany"},{"name":"Artificial Intelligence in Medical Imaging German Center for Neurodegenerative Diseases (DZNE)  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0626-9305","authenticated-orcid":false,"given":"Monique M. B.","family":"Breteler","sequence":"additional","affiliation":[{"name":"Population Health Sciences German Centre for Neurodegenerative Diseases (DZNE)  Bonn Germany"},{"name":"Institute for Medical Biometry, Informatics and Epidemiology (IMBIE) University of Bonn, University Hospital Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6184-458X","authenticated-orcid":false,"given":"N. Ahmad","family":"Aziz","sequence":"additional","affiliation":[{"name":"Population Health Sciences German Centre for Neurodegenerative Diseases (DZNE)  Bonn Germany"},{"name":"Institute for Medical Biometry, Informatics and Epidemiology (IMBIE) University of Bonn, University Hospital Bonn  Bonn Germany"},{"name":"Centre of Neurology, Clinic for Parkinson, Sleep &amp; Movement Disorders University of Bonn, University Hospital Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1053\u20108119(03)00336\u20107"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2015.10.019"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006\u20103495(94)80775\u20101"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2023.10.009"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropsychologia.2022.108207"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13879"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2023.101868"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2025.111181"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13629"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2014.06.011"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.112.680223"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2020.113061"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23158713"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0896\u20106273(02)00569\u2010x"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000200884"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3041"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2017.04.064"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596\u2010024\u201001085\u2010w"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0000000000001939"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380\u2010024\u201002604\u20107"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.hdy.6800717"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010023\u201033063\u20109"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000200782"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415\u2010022\u201011454\u20108"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2021.04.006"},{"key":"e_1_2_11_27_1","doi-asserted-by":"crossref","unstructured":"Mishra S. C.Pettigrew C.Ugonna et\u00a0al.2026.\u201cPlasma Inflammatory Markers and Brain White Matter Microstructure in Late Middle\u2010Aged and Older Adults.\u201dMedRxiv.https:\/\/doi.org\/10.64898\/2026.04.20.26351124.","DOI":"10.64898\/2026.04.20.26351124"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2007.12.035"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15557"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.123.21264"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255\u2010025\u201001244\u20107"},{"key":"e_1_2_11_32_1","first-page":"1","volume-title":"The Handbook of Aging and Cognition","author":"Raz N.","year":"2000"},{"key":"e_1_2_11_33_1","volume-title":"Encyclopedia of Life Sciences","author":"Raz N.","year":"2001"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000209864"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2015.09.071"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2025.03.008"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.24522"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2020.498056"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0306\u20104522(02)00664\u20104"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(25)00184\u20109"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0167884"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2018.00650"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X221133861"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003\u2010023\u201004741\u20101"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000010146"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X211058803"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2019.04.006"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2021.10.013"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.00081"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010150751"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.03.072"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70659","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.70659","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70659","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:10:25Z","timestamp":1787321425000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.70659"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":50,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1111\/acel.70659"],"URL":"https:\/\/doi.org\/10.1111\/acel.70659","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"2025-10-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70659"}}