作者
Logan Dumitrescu, Emily R Mahoney, Shubhabrata Mukherjee, Michael L Lee, William S Bush, Corinne D Engelman, Qiongshi Lu, David W Fardo, Emily H Trittschuh, Jesse Mez, Catherine Kaczorowski, Hector Hernandez Saucedo, Keith F Widaman, Rachel Buckley, Michael Properzi, Elizabeth Mormino, Hyun-Sik Yang, Tessa Harrison, Trey Hedden, Kwangsik Nho, Shea J Andrews, Doug Tommet, Niran Hadad, R Elizabeth Sanders, Douglas M Ruderfer, Katherine A Gifford, Annah M Moore, Francis Cambronero, Xiaoyuan Zhong, Neha S Raghavan, Badri Vardarajan, Alzheimer’s Disease Neuroimaging Initiative (ADNI), Alzheimer’s Disease Genetics Consortium (ADGC), A4 Study Team, Margaret A Pericak-Vance, Lindsay A Farrer, Li-San Wang, Carlos Cruchaga, Gerard Schellenberg, Nancy J Cox, Jonathan L Haines, C Dirk Keene, Andrew J Saykin, Eric B Larson, Reisa A Sperling, Richard Mayeux, David A Bennett, Julie A Schneider, Paul K Crane, Angela L Jefferson, Timothy J Hohman
发表日期
2020/8/1
期刊
Brain
卷号
143
期号
8
页码范围
2561-2575
出版商
Oxford University Press
简介
Approximately 30% of older adults exhibit the neuropathological features of Alzheimer’s disease without signs of cognitive impairment. Yet, little is known about the genetic factors that allow these potentially resilient individuals to remain cognitively unimpaired in the face of substantial neuropathology. We performed a large, genome-wide association study (GWAS) of two previously validated metrics of cognitive resilience quantified using a latent variable modelling approach and representing better-than-predicted cognitive performance for a given level of neuropathology. Data were harmonized across 5108 participants from a clinical trial of Alzheimer’s disease and three longitudinal cohort studies of cognitive ageing. All analyses were run across all participants and repeated restricting the sample to individuals with unimpaired cognition to identify variants at the earliest stages of disease. As expected, all …
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L Dumitrescu, ER Mahoney, S Mukherjee, ML Lee… - Brain, 2020