{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T12:59:03Z","timestamp":1790427543923,"version":"4.1.0"},"posted":{"date-parts":[[2026,9,23]]},"group-title":"Addiction Medicine","reference-count":25,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"funder":[{"award":["R01 AG065234, R01 AG084723, P01 AG026276, R01 AA029308, U10 AA008401, UL1TR002345"],"award-info":[{"award-number":["R01 AG065234, R01 AG084723, P01 AG026276, R01 AA029308, U10 AA008401, UL1TR002345"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Alcohol use disorder (AUD) is an established contributor to neurocognitive impairment and a major modifiable risk factor for dementia. However, the extent to which lifetime AUD interacts with aging to accelerate subtle cognitive trajectories prior to overt clinical dementia remains unclear.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To investigate whether a lifetime history of DSM-5 AUD and correlated indices of alcohol consumption are associated with accelerated age-related cognitive decline in middle-aged and older adults.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Participants (N = 1,421) were drawn from the Collaborative Study on the Genetics of Alcoholism (COGA) prospective longitudinal study. Lifetime AUD status (defined as 2 or more DSM-5 criteria endorsed at peak drinking) and drinking patterns were derived from the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA). Cognitive performance across multiple domains was evaluated using the NIH Toolbox Cognition Battery to yield Total, Fluid, and Crystallized Composite Scores. Linear mixed-effects models examined main effects of AUD and age, as well as an AUD-by-age interaction, controlling for testing site.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>At the time of cognitive assessment, the overall sample had a mean age of 52.5 years (SD = 14.5) with a mean longitudinal observation period of 25.0 years (SD = 4.7). The sample was 60% female, 40% male, 7% Hispanic, 23% non-Hispanic Black, 68% non-Hispanic White, 2% other race\/ethnicity. 64% met lifetime criteria for AUD (n = 908). While baseline mean cognitive composite scores were similar between those with and without AUD, lifetime AUD was significantly associated with steeper age-related decline for both the Total Composite score (interaction estimate = \u22120.092, 95% CI [\u22120.173, \u22120.010], p = 0.03) and Fluid Composite score (interaction estimate = \u22120.13, 95% CI [\u22120.220, \u22120.040], p = 0.005). No significant AUD-by-age interaction was observed for Crystallized Composite scores (interaction estimate = \u22120.026, 95% CI [\u22120.092, 0.041], p = 0.449). Based on model projections, the AUD-associated cognitive deficit on Total Composite scores was equivalent to 7.1 additional years of cognitive aging at age 60 (95% CI [\u22120.5, 14.7]) and 13.8 additional years at age 75 (95% CI [0.2, 27.3]). Measures of current (past-year) drinking status and current drinks per week showed no significant interaction with age.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>A lifetime history of AUD acts as a catalyst for cognitive aging, significantly steepening the trajectory of age-related decline in total and fluid cognitive functioning well before the onset of clinical dementia. Cross-sectional measures of current drinking failed to capture these effects, demonstrating that evaluating cumulative lifetime drinking history is important for assessing alcohol-related cognitive decline.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.22.26363720","type":"posted-content","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T03:15:17Z","timestamp":1790219717000},"source":"Crossref","is-referenced-by-count":0,"title":["Alcohol use disorder accelerates age-related cognitive decline"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5429-3799","authenticated-orcid":false,"given":"Sarah M.","family":"Hartz","sequence":"first","affiliation":[{"name":"Washington University in St. Louis"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacquelyn","family":"Meyers","sequence":"additional","affiliation":[{"name":"SUNY Downstate Health Sciences 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