{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T04:02:08Z","timestamp":1777953728477,"version":"3.51.4"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"National Insitute on Aging","award":["R01AG11380"],"award-info":[{"award-number":["R01AG11380"]}]},{"name":"National Insitute on Aging","award":["R01AG18712"],"award-info":[{"award-number":["R01AG18712"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Background:<\/jats:p>\n                  <jats:p>Traumatic brain injury (TBI) is a well-recognized risk factor for late-life cognitive decline. However, few studies have examined individual differences in sex and genetics, which may modify risk. We examined sex differences in gene-TBI interactions for dementia risk genes apolipoprotein E (APOE) and selected brain-derived neurotrophic factor (BDNF) single-nucleotide polymorphisms (SNPs) in predicting late-life cognitive decline.<\/jats:p>\n                  <jats:p>Methods:<\/jats:p>\n                  <jats:p>We studied 4293 individuals without dementia at baseline (mean age: 74.93, SD: 6.87\u2009years, 57% female). Approximately 25% reported a history of TBI. Linear mixed effects models examined associations between sex, TBI characteristics, APOE genotype, BDNF SNPs and their interactions, with cognitive decline.<\/jats:p>\n                  <jats:p>Results:<\/jats:p>\n                  <jats:p>Compared to males, females experienced fewer TBIs across the lifespan, the majority occurring in late-life. Number of TBI interacted with sex and APOE genotype such that female APOE \u03b54 allele carriers with multiple TBIs exhibited worse outcomes on global cognition (P &amp;lt; .001; eg, \u03b54+\/TBI2+ estimated marginal means [EMMs] from baseline to year 10 = \u221217.22 points compared with \u03b54-\/TBI2+ = \u22127.21), whereas males did not exhibit differential decline by APOE \u03b54 alleles and TBI number. BDNF Val66Met genotype showed trend-level moderation of TBI history and cognitive decline, with slower decline experienced by heterozygous individuals with multiple TBIs compared with homozygous major allele carriers. There were few significant associations between timing and severity of TBI with cognitive outcomes.<\/jats:p>\n                  <jats:p>Conclusions:<\/jats:p>\n                  <jats:p>These results underscore the importance of considering individual differences of sex and APOE and BDNF-related gene variants on the long-term cognitive effects of TBI.<\/jats:p>","DOI":"10.1093\/gerona\/glag011","type":"journal-article","created":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T12:33:12Z","timestamp":1768653192000},"source":"Crossref","is-referenced-by-count":0,"title":["Sex differences in genetic modifiers of traumatic brain injury and late-life cognitive decline: the Cache County study"],"prefix":"10.1093","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7523-2833","authenticated-orcid":false,"given":"Mikaela A","family":"Drewel","sequence":"first","affiliation":[{"name":"Department of Psychology, Utah State University , Logan, Utah,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Department of Psychology, Utah State University , Logan, Utah,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gail B","family":"Rattinger","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences, Binghamton University , Binghamton, New York,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mona","family":"Buhusi","sequence":"additional","affiliation":[{"name":"Department of Psychology, Utah State University , Logan, Utah,","place":["United States"]},{"name":"Alzheimer\u2019s Disease and Dementia Research Center, Utah State University , Logan, Utah,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JoAnn T","family":"Tschanz","sequence":"additional","affiliation":[{"name":"Department of Psychology, Utah State University , Logan, Utah,","place":["United States"]},{"name":"Alzheimer\u2019s Disease and Dementia Research Center, Utah State University , Logan, Utah,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"key":"2026050412365967200_glag011-B1","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1097\/JNN.0000000000000570","article-title":"A meta-analysis of dynamic prevalence of cognitive deficits in the acute, subacute, and chronic phases after traumatic brain injury","volume":"53","author":"Tsai","year":"2021","journal-title":"J Neurosci Nurs"},{"key":"2026050412365967200_glag011-B2","doi-asserted-by":"publisher","first-page":"3876","DOI":"10.1523\/JNEUROSCI.09-11-03876.1989","article-title":"Penetrating head injury in young adulthood exacerbates cognitive decline in later years","volume":"9","author":"Corkin","year":"1989","journal-title":". 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