{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T14:53:16Z","timestamp":1785855196309,"version":"3.56.0"},"reference-count":99,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"the National Institutes of Health","doi-asserted-by":"crossref","award":["R35CA197289, R35CA283926, and R01AG068193"],"award-info":[{"award-number":["R35CA197289, R35CA283926, and R01AG068193"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K08CA241337, P30AG010133, P30AG072976, P30CA008748, R01AG082348, R01CA129769, R01CA172119, R01CA237535, R01CA244673, R33AG075008, R56AG068086, U54CA137788"],"award-info":[{"award-number":["K08CA241337, P30AG010133, P30AG072976, P30CA008748, R01AG082348, R01CA129769, R01CA172119, R01CA237535, R01CA244673, R33AG075008, R56AG068086, U54CA137788"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institutes of Health National Cancer Institute","award":["P30CA51008"],"award-info":[{"award-number":["P30CA51008"]}]},{"name":"the Georgetown Lombardi Comprehensive Cancer Center for support of the Biostatistics and Bioinformatics Resource and the Non-Therapeutic Shared Resource"},{"name":"the UCLA Cousins Center for Psychoneuroimmunology"},{"name":"the Frank M. Ewing Foundation Endowed Chair of Hematology and Oncology"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Neural substrates of cancer-related cognitive impairment remain poorly understood, especially in older adults facing aging-related cognitive decline and comorbid chronic conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Breast cancer survivors aged \u226560 years (n\u2009=\u200964) and noncancer controls (n\u2009=\u200962) completed structural MRI and neuropsychological testing and self-reported cognition and health information at pretreatment baseline and 12- and 24-month follow-ups. Regional gray matter volume and brain age were evaluated using FreeSurfer and brainageR. Longitudinal linear mixed models tested effects of group, time, and group-by-time interactions on volume. Secondary analyses examined relationships between group, comorbidities, age, gray matter volume, and cognition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Survivors exhibited frontal (P\u2009=\u2009.025, q\u2009=\u20090.058), thalamic (P\u2009=\u2009.008, q\u2009=\u20090.052), and limbic (P\u2009=\u2009.015, q\u2009=\u20090.052) gray matter decline relative to controls over 24 months, with smaller effects in parietal (P\u2009=\u20090.055, q\u2009=\u20090.097) and temporal (P\u2009=\u20090.091, q\u2009=\u20090.127) regions. Survivors showed average yearly frontal and thalamic volume loss at twice the rate of controls (P\u2009&amp;lt;\u20090.05). Survivors with a high comorbidity burden (\u22653 comorbidities) exhibited the lowest frontal gray matter volume at all timepoints. A trend-level group-by-time interaction for brain age (P\u2009=\u20090.093) suggested accelerated brain aging in survivors. Survivors failed to show practice effects in the attention, processing speed, and executive functioning neuropsychological domain, whereas controls improved significantly over time (group-by-time interaction: P\u2009=\u20090.030).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Older breast cancer survivors tended to demonstrate gray matter decline and accelerated brain aging throughout the first 2 years of survivorship, with comorbidity burden amplifying frontal vulnerability. Findings highlight the need for longitudinal cognitive monitoring and targeted intervention, particularly for older survivors with high comorbidity burden.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration number<\/jats:title>\n                    <jats:p>ClinicalTrials.gov Identifier: NCT03451383.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jnci\/djag219","type":"journal-article","created":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T20:02:01Z","timestamp":1783281721000},"source":"Crossref","is-referenced-by-count":0,"title":["Longitudinal effects of comorbidities on brain structure and cognition in older breast cancer survivors"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6321-4717","authenticated-orcid":false,"given":"Chloe C","family":"Casagrande","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Georgetown University School of 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North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica N","family":"Bailey","sequence":"additional","affiliation":[{"name":"Department of Radiology and Imaging Sciences, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, and Indiana Alzheimer\u2019s Disease Research Center, Indiana University School of Medicine , Indianapolis, IN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1500-930X","authenticated-orcid":false,"given":"Kathleen","family":"Van Dyk","sequence":"additional","affiliation":[{"name":"Department of Supportive Care Medicine, Center for Cancer and Aging, City of Hope , Duarte, CA,","place":["United States"]},{"name":"Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine and UCLA Jonsson Comprehensive Cancer Center, University of California at Los Angeles , Los Angeles, CA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7332-6165","authenticated-orcid":false,"given":"James C","family":"Root","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center , New York, NY,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7936-2818","authenticated-orcid":false,"given":"Tim A","family":"Ahles","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center , New York, NY,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5516-0819","authenticated-orcid":false,"given":"Judith E","family":"Carroll","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine and UCLA Jonsson Comprehensive Cancer Center, University of California at Los Angeles , Los Angeles, CA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2490-005X","authenticated-orcid":false,"given":"Jeanne S","family":"Mandelblatt","sequence":"additional","affiliation":[{"name":"Institute for Cancer and Aging Research (I-CARE) and Cancer Prevention and Control Program at Georgetown Lombardi Comprehensive Cancer Center and Departments of Oncology and Medicine at Georgetown University School of Medicine, Georgetown University , Washington, DC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1376-8532","authenticated-orcid":false,"given":"Andrew J","family":"Saykin","sequence":"additional","affiliation":[{"name":"Department of Radiology and Imaging Sciences, Indiana University Melvin 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