{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T16:03:38Z","timestamp":1789747418406,"version":"4.0.1"},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"vor","delay-in-days":84,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["P50 HD105353"],"award-info":[{"award-number":["P50 HD105353"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG062167"],"award-info":[{"award-number":["R01AG062167"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG085592"],"award-info":[{"award-number":["R01AG085592"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P30AG062715"],"award-info":[{"award-number":["P30AG062715"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["RF1AG027161"],"award-info":[{"award-number":["RF1AG027161"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG054059"],"award-info":[{"award-number":["R01AG054059"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR002373"],"award-info":[{"award-number":["UL1TR002373"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"publisher","award":["S10 OD030415"],"award-info":[{"award-number":["S10 OD030415"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["A&amp;D Transl Res &amp; Clin Interv"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>The accumulation of core Alzheimer's disease (AD) pathology contributes to cognitive decline. Cardiorespiratory fitness (CRF) influences AD pathological progression resulting in improvement or maintenance of cognitive function with age. CRF\u2010related differences in accumulation rates or risk of reaching clinically relevant AD biomarker levels, and potentially interactive effects of core AD pathology and CRF on cognitive decline, remain largely unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Participants (\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a0533; Mean\n                      <jats:sub>AGE<\/jats:sub>\n                      \u00a0=\u00a065, 70% female) from the Wisconsin Alzheimer's Disease Research Center and the Wisconsin Registry for Alzheimer's Prevention underwent serial blood draws, and cognitive and imaging assessments (Mean\n                      <jats:sub>Follow\u2010up<\/jats:sub>\n                      \u00a0=\u00a06.0 years). Positron emission tomography (PET) imaging of amyloid beta (A\u03b2) and tau (T) and plasma phosphorylated tau\u2010217 (p\u2010tau217) were used to determine biomarker status (\u00b1). Sex\u2010specific estimated CRF (eCRF) tertiles were created using a validated equation. Kaplan\u2013Meier survival curves and Cox proportional hazards examined the risk of becoming biomarker\u2010positive. Linear mixed\u2010effects models, stratified by biomarker status, estimated associations between baseline eCRF and core AD biomarker accumulation, and whether eCRF modified relationships between biomarker accumulation and cognitive decline.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>There were no significant relationships between eCRF and biomarker trajectories. However, those in high eCRF group who were A\u03b2\u2212 at baseline had a significantly lower risk of becoming biomarker\u2010positive (A\u03b2\u2010PET: HR, 95% confidence interval [CI]\u00a0=\u00a00.42, 0.20\u20130.88; p\u2010tau\u2010217: 0.45, 0.21\u20130.97) compared to the low eCRF group. The detrimental relationship between A\u03b2 accumulation and cognitive decline was significantly attenuated for A\u03b2+\/T+ with high eCRF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Although eCRF did not influence core AD biomarker accumulation trajectories, high eCRF seems protective against becoming biomarker\u2010positive and attenuates the known deleterious relationship between biomarker accumulation and cognitive decline in A\u03b2+\/T+.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>High estimated cardiorespiratory fitness (eCRF) is associated with a lesser likelihood of becoming AD biomarker positive.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>High eCRF did not alter biomarker accumulation in those positive for Alzheimer's disease (AD) pathology.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>High eCRF attenuated the relationship between AD biomarkers and cognitive decline.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Innovative methods: Stratifying analyses by amyloid beta and tau status.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/trc2.70122","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T01:13:45Z","timestamp":1750814025000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The impact of estimated cardiorespiratory fitness on Alzheimer's disease biomarkers and their relationships with cognitive decline"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9919-0577","authenticated-orcid":false,"given":"Adam J","family":"Paulsen","sequence":"first","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center Department of Medicine University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"},{"name":"Wisconsin Alzheimer's Institute  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ira","family":"Driscoll","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center Department of Medicine University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"},{"name":"Wisconsin Alzheimer's Institute  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianne M.","family":"Breidenbach","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center Department of Medicine University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"},{"name":"Wisconsin Alzheimer's Institute  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Glittenberg","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center Department of Medicine University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"},{"name":"Wisconsin Alzheimer's Institute  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah R.","family":"Lose","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center Department of Medicine University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"},{"name":"Wisconsin Alzheimer's Institute  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Ma","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center Department of Medicine University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Sager","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center Department of Medicine University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia M.","family":"Carlsson","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center Department of Medicine University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"},{"name":"Wisconsin Alzheimer's Institute  Madison Wisconsin USA"},{"name":"Geriatric Research Education and Clinical Center William S. Middleton VA Hospital  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine L.","family":"Gallagher","sequence":"additional","affiliation":[{"name":"Geriatric Research Education and Clinical Center William S. Middleton VA Hospital  Madison Wisconsin USA"},{"name":"Department of Neurology University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce P.","family":"Hermann","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Institute  Madison Wisconsin USA"},{"name":"Department of Neurology University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology Sahlgrenska Academy at the University of Gothenburg, Gothenburg  M\u00f6lndal Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital  G\u00f6teborg Sweden"},{"name":"Paris Brain Institute ICM, Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital, Sorbonne University  Paris France"},{"name":"Neurodegenerative Disorder Research Center Division of Life Sciences and Medicine and Department of Neurology Institute on Aging and Brain Disorders University of Science and Technology of China and First Affiliated Hospital of USTC  Hefei Anhui P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center Department of Medicine University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"},{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology Sahlgrenska Academy at the University of Gothenburg, Gothenburg  M\u00f6lndal Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital  G\u00f6teborg Sweden"},{"name":"Department of Neurodegenerative Disease UCL Institute of Neurology  Queen Square London UK"},{"name":"UK Dementia Research Institute at UCL  London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Asthana","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center Department of Medicine University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"},{"name":"Wisconsin Alzheimer's Institute  Madison Wisconsin USA"},{"name":"Geriatric Research Education and Clinical Center William S. Middleton VA Hospital  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sterling C.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center Department of Medicine University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"},{"name":"Wisconsin Alzheimer's Institute  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobey J.","family":"Betthauser","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center Department of Medicine University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"},{"name":"Wisconsin Alzheimer's Institute  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley T.","family":"Christian","sequence":"additional","affiliation":[{"name":"Department of Medical Physics Department of Medicine University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dane B.","family":"Cook","sequence":"additional","affiliation":[{"name":"William S. Middleton Memorial Veterans Hospital  Madison Wisconsin USA"},{"name":"Department of Kinesiology University of Wisconsin School of Education 1300 University Avenue, 285 Medical Sciences Center  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozioma C.","family":"Okonkwo","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center Department of Medicine University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"},{"name":"Wisconsin Alzheimer's Institute  Madison Wisconsin USA"},{"name":"Geriatric Research Education and Clinical Center William S. Middleton VA Hospital  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010024\u201002988\u20107"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.003"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.118.209650"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awae116"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010024\u201002869\u2010z"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.018"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13809"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12212"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glw130"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000964"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003862"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000006954"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.09.008"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1355617715000843"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12330"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357\u2010024\u201001130\u20102"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010181175"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0244893"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13556"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005354"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000027055"},{"issue":"1","key":"e_1_2_9_23_1","first-page":"62","article-title":"Wisconsin Alzheimer's Disease Research Center\u2010Notable Discoveries and Accomplishments in Dementia Research","volume":"123","author":"Asthana S","year":"2024","journal-title":"WMJ Off Publ State Med Soc Wis"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadm.2017.11.007"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010221249"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11682\u2010014\u20109325\u20109"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amepre.2005.06.004"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2013.09.028"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010160528"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz378"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010006\u20100127\u2010z"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.5319"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14100"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadm.2018.11.006"},{"key":"e_1_2_9_35_1","volume-title":"A Compendium of Neuropsychological Tests: Administration, Tests, Norms, and Commentary","author":"Sherman EMS","year":"2020"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12007"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25395"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010022\u201002049\u2010x"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000200270"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40814\u2010022\u201001200\u20102"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0244893"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000006075"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2015.251"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582\u2010024\u201000962\u2010y"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.2338"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000009724"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12966\u2010024\u201001663\u2010x"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glae161"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2022.0976"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11682\u2010019\u201000068\u2010w"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(25)00184\u20109"}],"container-title":["Alzheimer's &amp; Dementia: Translational Research &amp; Clinical Interventions"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/trc2.70122","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T09:25:16Z","timestamp":1761470716000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/trc2.70122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4]]},"references-count":50,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1002\/trc2.70122"],"URL":"https:\/\/doi.org\/10.1002\/trc2.70122","archive":["Portico"],"relation":{},"ISSN":["2352-8737","2352-8737"],"issn-type":[{"value":"2352-8737","type":"print"},{"value":"2352-8737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4]]},"assertion":[{"value":"2025-02-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70122"}}