{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:08:48Z","timestamp":1780636128498,"version":"3.54.1"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"vor","delay-in-days":75,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["A&amp;amp;D Transl Res &amp;amp; Clin Interv"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Alzheimer's disease and related dementias (ADRD) remain a leading cause of morbidity and mortality. Poor cardiorespiratory fitness (CRF) has been identified as a potential risk factor for ADRD. Since CRF is a modifiable risk factor, we evaluated the association between CRF changes over time and ADRD risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Our cohort consisted of US Veterans (mean age 60.7\u00b19.0 years; male,\n                      <jats:italic>n<\/jats:italic>\n                      = 128,749; and female,\n                      <jats:italic>n<\/jats:italic>\n                      = 5,421). All completed two standardized exercise treadmill tests (ETT) between 2000 and 2017, at least 1 year apart (mean 3.5\u00b12.7 years), with no evidence of ADRD at the time of both ETTs. We assigned participants to one of three age\u2010 and gender\u2010specific CRF categories based on peak metabolic equivalents (METs) achieved during the initial ETT and five categories based on CRF changes at the final ETT. Cox proportional hazard models adjusted for age, comorbidities, and medications were used to evaluate ADRD risk across CRF categories.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      During the up to 15.0 years of follow\u2010up (mean 7.2 years; interquartile range [IQR] 4.3\u20139.9 years), totaling 966,337 person\u2010years, 10,699 ADRD cases occurred (11.1 events\/1000 person\u2010years). Compared to the Low\u2010fit group, ADRD risk decreased progressively with increased CRF and was 22% lower (hazard ratio [HR] 0.78; 95% confidence interval [CI]: 0.75\u20100.81;\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.0001) for Moderate\u2010fit individuals and 30% lower (HR 0.70, 95% CI: 0.67\u20130.73;\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.0001) for High\u2010fit individuals. Compared to Low\u2010fit individuals with no CRF change, an increase of 0.1\u2013&lt;2.0 METs was associated with a 13% lower ADRD risk (HR 0.87, 95% CI 0.79\u20130.95;\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.0001), while an increase of \u22652.0 METs was associated with a 24% lower risk (HR 0.76, 95% CI 0.70\u20130.83;\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.0001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>We observed an inverse and independent association between CRF and ADRD risk. An improvement in CRF of approximately \u22651.0 MET led to a lower risk of ADRD in Low\u2010fit individuals. These findings may have considerable clinical and public health significance in reducing ADRD risk.<\/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>Poor cardiorespiratory fitness (CRF) has been identified as a potential risk factor for Alzheimer's disease and related dementias (ADRD). Thus, we assessed the potential impact of changes in CRF over time on ADRD risk.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>CRF changes reflected inverse and proportional changes in ADRD risk.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Low\u2010fit individuals who improved their CRF by \u22650.1 metabolic equivalents (METs) had a 13%\u201324% lower ADRD risk. Conversely, a decline in CRF by \u22652.0 METs was associated with a 14% increased ADRD risk among Moderate\u2010fit and a 18% increase among High\u2010fit individuals.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/trc2.70171","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T06:35:25Z","timestamp":1765866925000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Long\u2010term changes in cardiorespiratory fitness and incidence of Alzheimer's disease and related dementias among US Veterans"],"prefix":"10.1002","volume":"11","author":[{"given":"Peter","family":"Kokkinos","sequence":"first","affiliation":[{"name":"Department of Kinesiology and Health School of Arts and Sciences Rutgers University  New Brunswick New Jersey USA"},{"name":"Department of Cardiology Washington DC, VA Medical Center  Washington District of Columbia USA"},{"name":"George Washington University  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Cardiology Washington DC, VA Medical Center  Washington District of Columbia USA"},{"name":"George Washington University  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Zamrini","sequence":"additional","affiliation":[{"name":"George Washington University  Washington District of Columbia USA"},{"name":"Department of Cardiology Irvine Clinical Research  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Faselis","sequence":"additional","affiliation":[{"name":"Department of Cardiology Washington DC, VA Medical Center  Washington District of Columbia USA"},{"name":"George Washington University  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Sui","sequence":"additional","affiliation":[{"name":"Department of Exercise Science University of South Carolina  Columbia South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charity J","family":"Morgan","sequence":"additional","affiliation":[{"name":"Department of Cardiology University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen M.","family":"Sheriff","sequence":"additional","affiliation":[{"name":"Department of Cardiology Washington DC, VA Medical Center  Washington District of Columbia USA"},{"name":"George Washington University  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Myers","sequence":"additional","affiliation":[{"name":"Cardiology 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