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This study aimed to investigate the effects of A\u03b2 and microglial responses on global cognitive impairment.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>In this longitudinal study, 28 patients with mild cognitive impairment and 11 healthy controls underwent <jats:sup>11<\/jats:sup>C\u2010PK11195 and <jats:sup>11<\/jats:sup>C\u2010Pittsburgh compound B positron emission tomography (PET), structural magnetic resonance imaging scans, and global cognitive ratings at baseline and 2\u2010year follow\u2010up. Correlations between PET uptake and global cognition were assessed. Additionally, the mediation effect of the microglial response on the association between A\u03b2 load and global cognition was assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>A\u03b2 load and the microglial response were both independently detrimental to global cognitive performance at baseline; however, at 2\u2010year follow\u2010up the association between A\u03b2 load and global cognitive ratings was partially mediated by the microglial response.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>As AD progresses, the associated microglial response partially mediates the detrimental effect of aggregated A\u03b2 on cognition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>This was a longitudinal study of amyloid beta (A\u03b2), microglial responses, and global cognitive performance.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>A\u03b2 and microglial responses both affect cognition in early Alzheimer's disease.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Microglial response partially mediates the effect of A\u03b2 on cognition in later stages.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.14298","type":"journal-article","created":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T07:04:20Z","timestamp":1728630260000},"page":"8028-8037","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Microglial responses partially mediate the effect of A\u03b2 on cognition in Alzheimer's disease"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5721-9885","authenticated-orcid":false,"given":"Lasse S.","family":"Madsen","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine Center of Functionally Integrative Neuroscience Aarhus University  Aarhus 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