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There is increasing interest in the preclinical or asymptomatic phase of Alzheimer\u2019s disease.<\/jats:p>\n                  <jats:p>Here we examined in 35 cognitively intact older adults (age range 52\u201378\u2009years at baseline, 17 male) in a longitudinal study design the association between accumulation of amyloid over a 5\u20136-year period, measured using PET, and functional changes in the language network measured over the same time period using task-related functional MRI. In the same participants, we also determined the association between the longitudinal functional MRI changes and a cross-sectional measure of tau load as measured with 18F-AV1451 PET.<\/jats:p>\n                  <jats:p>As predicted, the principal change occurred in posterior temporal cortex. In the cortex surrounding the right superior temporal sulcus, the response amplitude during the associative-semantic versus visuo-perceptual task increased over time as amyloid load accumulated (Pcorrected = 0.008). In a whole-brain voxel-wise analysis, amyloid accumulation was also associated with a decrease in response amplitude in the left inferior frontal sulcus (Pcorrected = 0.009) and the right dorsomedial prefrontal cortex (Pcorrected = 0.005). In cognitively intact older adults, cross-sectional tau load was not associated with longitudinal changes in functional MRI response amplitude.<\/jats:p>\n                  <jats:p>Our findings confirm the central role of the neocortex surrounding the posterior superior temporal sulcus as the area of predilection within the language network in the earliest stages of Alzheimer\u2019s disease. Amyloid accumulation has an impact on cognitive brain circuitry in the asymptomatic phase of Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.1093\/brain\/awab335","type":"journal-article","created":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T15:55:47Z","timestamp":1631634947000},"page":"3756-3768","source":"Crossref","is-referenced-by-count":25,"title":["Changes in the language system as amyloid-\u03b2 accumulates"],"prefix":"10.1093","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7964-7963","authenticated-orcid":false,"given":"Mariska","family":"Reinartz","sequence":"first","affiliation":[{"name":"Laboratory for Cognitive Neurology, Department of Neurosciences, Leuven Brain Institute, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvy","family":"Gabel","sequence":"additional","affiliation":[{"name":"Laboratory for Cognitive Neurology, Department of Neurosciences, Leuven Brain Institute, KU Leuven, 3000 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Neurosciences, Leuven Brain Institute, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffi","family":"De Meyer","sequence":"additional","affiliation":[{"name":"Laboratory for Cognitive Neurology, Department of Neurosciences, Leuven Brain Institute, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koen","family":"Van Laere","sequence":"additional","affiliation":[{"name":"Division of Nuclear Medicine, UZ Leuven, 3000 Leuven, Belgium"},{"name":"Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Sunaert","sequence":"additional","affiliation":[{"name":"Translational MRI, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Dupont","sequence":"additional","affiliation":[{"name":"Laboratory for 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