{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:58:44Z","timestamp":1791244724303,"version":"4.1.0"},"posted":{"date-parts":[[2026,1,23]]},"group-title":"Epidemiology","reference-count":35,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Initial data indicate SARS-CoV-2 and herpes zoster negatively impact cognition, but studies examining their independent or synergistic impact specifically for late-onset Alzheimer disease (LOAD) risk are lacking. Retrospective cohort analysis of older individuals (age \u226565 between January 20, 2020 and May 16, 2025; n\u223c1.5 million) from the U.S. National Clinical Cohort Collaborative (N3C) COVID-19 Enclave indicates that, in adjusted Cox proportional hazard models, those with \u22651 reported COVID-19 infection were at increased LOAD risk compared with those with no reported infection (HR=1.13, 95% CI: 1.10-1.16). Recombinant zoster vaccinated patients had decreased LOAD risk regardless of sex, race, age at baseline and number of clinic visits (HR=0.71, 95% CI: 0.69-0.74); however, COVID-19 infection mitigated the protective effect of the vaccination. Recombinant zoster vaccination and reduced exposure to COVID-19 infection in the later decades of life may reduce the risk of developing Alzheimer disease over at least a five-year period.<\/jats:p>","DOI":"10.64898\/2026.01.21.26344555","type":"posted-content","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T22:20:50Z","timestamp":1769206850000},"source":"Crossref","is-referenced-by-count":1,"title":["Opposing and antagonizing effects of SARS-CoV-2\/COVID-19 infection and recombinant zoster vaccination on the risk of late-onset Alzheimer disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4910-0264","authenticated-orcid":false,"given":"Carly M.","family":"Rose","sequence":"first","affiliation":[{"name":"Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiying","family":"Liu","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9729-6519","authenticated-orcid":false,"given":"William S.","family":"Bush","sequence":"additional","affiliation":[{"name":"Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan L.","family":"Haines","sequence":"additional","affiliation":[{"name":"Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott M.","family":"Williams","sequence":"additional","affiliation":[{"name":"Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6437-6248","authenticated-orcid":false,"given":"Dana C.","family":"Crawford","sequence":"additional","affiliation":[{"name":"Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026042200350615000_2026.01.21.26344555v2.1","doi-asserted-by":"crossref","first-page":"3800","DOI":"10.1021\/acschemneuro.4c00339","article-title":"Alzheimer\u2019s Disease: Exploring the Landscape of Cognitive Decline","volume":"15","year":"2024","journal-title":"ACS Chemical Neuroscience"},{"key":"2026042200350615000_2026.01.21.26344555v2.2","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1212\/CON.0000000000000700","article-title":"Late-onset Alzheimer Disease","volume":"25","year":"2019","journal-title":"Continuum"},{"key":"2026042200350615000_2026.01.21.26344555v2.3","doi-asserted-by":"crossref","first-page":"e70235","DOI":"10.1002\/alz.70235","article-title":"2025 Alzheimer\u2019s disease facts and figures","volume":"21","year":"2025","journal-title":"Alzheimer\u2019s & Dementia"},{"key":"2026042200350615000_2026.01.21.26344555v2.4","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1997.03550160069041"},{"key":"2026042200350615000_2026.01.21.26344555v2.5","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1001\/jamaneurol.2023.3599","article-title":"APOE Genotype and Alzheimer Disease Risk Across Age, Sex, and Population Ancestry","volume":"80","year":"2023","journal-title":"JAMA Neurology"},{"key":"2026042200350615000_2026.01.21.26344555v2.6","doi-asserted-by":"crossref","unstructured":"Sharp, E.S. & Gatz, M . 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