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To investigate potential predictors of LLD, we assessed cognitive scores and neurodegenerative and vascular biomarkers in healthy older adults who later developed depression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Longitudinal data from the Alzheimer's Disease Neuroimaging Initiative of 241 cognitively unimpaired and non\u2010depressed older adults aged 56\u201390 at baseline with at least 4\u00a0years of follow\u2010up were included. Participants were classified based on whether they developed an incident depression (<jats:italic>n<\/jats:italic>\u00a0=\u00a096) or not (<jats:italic>n<\/jats:italic>\u00a0=\u00a0145). Cognitive measures of memory, executive functioning, and language, and biomarkers proposed to be related to LLD: hippocampal volume, white matter hyperintensity volume (WMH), and cortical and cerebrospinal fluid (CSF) amyloid beta levels, were compared between the incident depression and the never\u2010depressed groups at four time points: at baseline, the visit prior to onset, at onset, and after the onset of depression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the incident depression group, there was a mild decline in cognitive scores from baseline to the visit before depression onset compared with the never\u2010depressed group. The cognitive differences between the groups became more marked after depression onset. Baseline cortical amyloid burden, CSF amyloid beta levels, and WMH were significant predictors of incident depression. Compared to the non\u2010depressed group, hippocampal volume was not reduced before onset, but was reduced following depression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Amyloid pathology and WMH can predict future development of LLD in cognitively unimpaired individuals and may be involved in precipitating vulnerability for depression in older adults.<\/jats:p><\/jats:sec>","DOI":"10.1002\/gps.5686","type":"journal-article","created":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T15:48:49Z","timestamp":1643644129000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Brain pathology and cognitive scores prior to onset of late\u2010life depression"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6070-4921","authenticated-orcid":false,"given":"Ina S.","family":"Almdahl","sequence":"first","affiliation":[{"name":"Department of Old Age Psychiatry Oslo University Hospital Oslo Norway"},{"name":"Institute of Clinical Medicine Faculty of Medicine University of Oslo Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingrid","family":"Agartz","sequence":"additional","affiliation":[{"name":"Department of Psychiatric Research Diakonhjemmet Hospital Oslo Norway"},{"name":"Norwegian Centre for Mental Disorders Research (NORMENT) Institute of Clinical Medicine University of Oslo Oslo Norway"},{"name":"Department of Clinical Neuroscience Centre for Psychiatric Research, Karolinska Institutet Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth","family":"Hugdahl","sequence":"additional","affiliation":[{"name":"Department of Biological and Medical Psychology University of Bergen Bergen Norway"},{"name":"Division of Psychiatry Haukeland University Hospital Bergen Norway"},{"name":"Department of Radiology Haukeland University Hospital Bergen Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria S.","family":"Korsnes","sequence":"additional","affiliation":[{"name":"Department of Old Age Psychiatry Oslo University Hospital Oslo Norway"},{"name":"Department of Psychology Faculty of Social Sciences University of Oslo Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"for the Alzheimer\u2019s Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,2,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32154-2"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30925-9"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psc.2013.07.001"},{"key":"e_1_2_10_5_1","unstructured":"WHO.2017. 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