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HSV\u20101 antibodies were assayed in baseline sera collected from 2009\u20132015. Linear mixed\u2010effects models were used to compare outcomes by HSV\u20101 seropositivity and high HSV\u20101 IgG titres\/IgM status.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There was no association between baseline HSV\u20101 seropositivity and rates of cognitive decline or whole brain atrophy. Having high HSV\u20101 IgG titres\/IgM was associated with a slightly greater decline in MMSE points per year (difference in slope\u2009\u2212\u20090.365, 95% CI: \u22120.958 to \u22120.072), but not with rate of whole brain atrophy. Symptomatic mutation carriers declined fastest on both MMSE and BSI measures, however, this was not influenced by HSV\u20101. Among asymptomatic mutation carriers, rates of decline on MMSE and BSI were slightly greater among those who were HSV\u20101 seronegative. Among mutation\u2010negative individuals, no differences were seen by HSV\u20101. Stratifying by <jats:italic>APOE4<\/jats:italic> status yielded inconsistent results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>We found no evidence for a major role of HSV\u20101, measured by serum antibodies, in cognitive decline or whole brain atrophy among individuals at high risk of early\u2010onset AD.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51669","type":"journal-article","created":{"date-parts":[[2022,10,3]],"date-time":"2022-10-03T09:13:19Z","timestamp":1664788399000},"page":"1727-1738","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Herpes simplex virus and rates of cognitive decline or whole brain atrophy in the Dominantly Inherited Alzheimer 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