{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T14:07:37Z","timestamp":1789135657703,"version":"build-2803163510"},"posted":{"date-parts":[[2026,9,8]]},"group-title":"Neurology","reference-count":42,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To evaluate whether educational attainment and Alzheimer disease genetic risk were associated with GLP-1 receptor agonist initiation and dementia incidence and whether adjustment for these measured factors materially changed the estimated association between GLP-1 receptor agonist initiation and incident dementia among adults with type 2 diabetes.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Research Design and Methods<\/jats:title>\n                  <jats:p>We conducted an observational cohort study using linked electronic health record, survey, and genetic data from 14,364 All of Us Research Program participants with type 2 diabetes. We estimated associations of educational attainment and Alzheimer disease genetic risk with treatment initiation and incident dementia and compared GLP-1 receptor agonist initiators with initiators of non-sodium-glucose cotransporter 2 inhibitor second-line therapies, with a separate sodium-glucose cotransporter 2 inhibitor comparison. Models were estimated before and after additional adjustment for educational attainment, APOE \u03b54, and non-APOE genetic risk.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Among 14,364 participants (mean age, 60.2 years; 54.2% female), the mean follow-up duration was 4.3 years. The estimated hazard ratio for dementia comparing GLP-1 receptor agonist initiation with non-SGLT2 inhibitor second-line therapy was 0.85 (95% CI 0.64-1.12) before adjustment for education or Alzheimer disease genetic risk and 0.84 (95% CI 0.64-1.12) after adjustment for educational attainment, APOE \u03b54, and non-APOE genetic risk.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Among adults with type 2 diabetes, adjustment for measured educational attainment and Alzheimer disease genetic susceptibility produced little change in the estimated association between GLP-1 receptor agonist initiation and incident dementia. These findings do not exclude confounding by these factors in other populations or residual confounding from socioeconomic, clinical, behavioral, and health-care-related factors.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>Observational studies have reported associations between GLP-1 receptor agonist use and lower dementia risk, but important social and genetic factors are often unavailable in electronic health record data.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>We examined whether educational attainment and Alzheimer disease genetic susceptibility were associated with treatment initiation and dementia and whether adjustment for these factors changed GLP-1 receptor agonist\u2013dementia estimates.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Adding measured education and genetic susceptibility produced little change in the estimated conditional hazard ratios.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>These results do not exclude residual confounding and should not be interpreted as evidence that GLP-1 receptor agonists prevent dementia.<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.04.26362304","type":"posted-content","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T15:24:36Z","timestamp":1788881076000},"source":"Crossref","is-referenced-by-count":0,"title":["Education and Alzheimer Disease Genetic Risk in Associations of GLP-1 Receptor Agonists With Dementia Among Adults With Type 2 Diabetes"],"prefix":"10.64898","author":[{"given":"Jingxuan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115"},{"name":"Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02129"},{"name":"Department of Epidemiology, Boston University, Boston, MA 02118"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M.","family":"Pederson","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Boston University, Boston, MA 02118"},{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94158"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Flanders","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Brown University, Providence, RI 02903"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minhyuk","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94158"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Buto","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Boston University, Boston, MA 02118"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendra D.","family":"Sims","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Boston University, Boston, MA 02118"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruijia","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Boston University, Boston, MA 02118"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elyse","family":"Couch","sequence":"additional","affiliation":[{"name":"Department of Health Services, Policy, & Practice, Brown University, Providence, RI 02903"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Gilsanz","sequence":"additional","affiliation":[{"name":"Division of Research, Kaiser Permanente Northern California, Pleasanton CA 94588"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaleen N.","family":"Hayes","sequence":"additional","affiliation":[{"name":"Department of Health Services, Policy, & Practice, Brown University, Providence, RI 02903"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew R.","family":"Zullo","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Brown University, Providence, RI 02903"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Stokes","sequence":"additional","affiliation":[{"name":"Division of Research, Kaiser Permanente Northern California, Pleasanton CA 94588"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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