{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:33:56Z","timestamp":1776213236895,"version":"3.50.1"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"National Institute on Aging, National Institutes of Health"},{"name":"Veteran\u2019s Administration"},{"name":"National Institute on Aging at the National Institutes of Health","award":["R01 AG050595"],"award-info":[{"award-number":["R01 AG050595"]}]},{"name":"National Institute on Aging at the National Institutes of Health","award":["R01 AG076838"],"award-info":[{"award-number":["R01 AG076838"]}]},{"name":"National Institute on Aging at the National Institutes of Health","award":["R01 AG037985"],"award-info":[{"award-number":["R01 AG037985"]}]},{"name":"National Institute on Aging at the National Institutes of Health","award":["R01 AG064955"],"award-info":[{"award-number":["R01 AG064955"]}]},{"name":"National Institute on Aging at the National Institutes of Health","award":["K01 AG081559"],"award-info":[{"award-number":["K01 AG081559"]}]},{"name":"National Institute on Aging at the National Institutes of Health","award":["K01 AG063805"],"award-info":[{"award-number":["K01 AG063805"]}]},{"name":"National Institute on Aging at the National Institutes of Health","award":["K01 AG084815"],"award-info":[{"award-number":["K01 AG084815"]}]},{"name":"National Institute on Aging at the National Institutes of Health","award":["P01 AG055367"],"award-info":[{"award-number":["P01 AG055367"]}]},{"name":"National Institute of Mental Health at the National Institutes of Health","award":["R25 MH101072"],"award-info":[{"award-number":["R25 MH101072"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cumulative deficit frailty (CDF) is a syndrome characterized by the accumulation of negative physical, functional and psychosocial insults. Accumulation of CDF and changes in brain structure both occur during the transition to older age and are associated with the development of Alzheimer\u2019s disease (AD) and related dementias. However, how these phenomena are temporally related to each other during the aging process is not well understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We examined bidirectional relationships between CDF and brain structure using structural MRI-based brain-predicted age difference and an AD brain signature. Longitudinal MRI and questionnaire-based data were collected from men in the Vietnam Era Twin Study of Aging at three study waves (average ages 56, 62, and 68).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Best-fitting longitudinal random intercepts cross-lagged panel models support the strong overall association between CDF and brain structural integrity with significant covariance between random intercepts for CDF and brain-predicted age difference (r\u2009=\u20090.36, p\u2009&amp;lt;\u2009.001) and between CDF and AD brain signature (r = \u22120.16, p\u2009=\u2009.005) after controlling for chronological age, smoking, race\/ethnicity, and education. Significant bidirectional negative cross-lagged associations suggested attenuation over time of the association between CDF and nonspecific brain aging (\u03b2s = \u22120.33 to \u22120.23, p\u2009\u2264\u2009.012) but not between CDF and AD brain signature.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CDF was associated with age-related brain structure via strong time-invariant common variance as well as weaker across-time factors. By contrast, the association between CDF and AD-related brain structure was via moderate common variance and was not temporally dynamic. Together, this suggests that CDF is differentially associated with age-related and AD-related brain changes and may be a clinically relevant risk factor for pathological brain aging.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/gerona\/glaf283","type":"journal-article","created":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T12:55:46Z","timestamp":1766235346000},"source":"Crossref","is-referenced-by-count":1,"title":["Association of cumulative deficit frailty with brain age and Alzheimer\u2019s disease-related brain structure starting in late-middle age"],"prefix":"10.1093","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5719-9028","authenticated-orcid":false,"given":"Jack F V","family":"Hunt","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University of California San Diego, La Jolla , California,","place":["United States"]},{"name":"Department of Psychiatry, University of Washington , Seattle, Washington,","place":["United 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California,","place":["United States"]},{"name":"Center for Behavior Genetics of Aging, University of California, La Jolla , San Diego, California,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5702-5995","authenticated-orcid":false,"given":"Tyler R","family":"Bell","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California San Diego, La Jolla , California,","place":["United States"]},{"name":"Center for Behavior Genetics of Aging, University of California, La Jolla , San Diego, California,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0406-9024","authenticated-orcid":false,"given":"Rongxiang","family":"Tang","sequence":"additional","affiliation":[{"name":"Center for Behavior Genetics of Aging, University of California, La Jolla , San Diego, California,","place":["United 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