@article{9ee00e1ae80343bdabc22bdc2e2f9776,
title = "Learning deficit in cognitively normal apoe ε4 carriers with low β-amyloid",
abstract = "Introduction: In cognitively normal (CN) adults, increased rates of amyloid beta (Aβ) accumulation can be detected in low Aβ (Aβ–) apolipoprotein E (APOE) ε4 carriers. We aimed to determine the effect of ε4 on the ability to benefit from experience (ie, learn) in Aβ–CNs. Methods: Aβ– CNs(n= 333) underwent episodic memory assessments every 18 months for 108 months. A subset (n = 48) completed the Online Repeatable Cognitive Assessment-Language Learning Test (ORCA-LLT) over 6 days. Results: Aβ– ε4 carriers showed significantly lower rates of improvement on episodic memory over 108 months compared to non-carriers (d = 0.3). Rates of learning on the ORCA-LLT were significantly slower in Aβ– ε4 carriers compared to non-carriers (d = 1.2). Discussion: In Aβ– CNs,ε4 is associated with a reduced ability to benefit from experience. This manifested as reduced practice effects (small to moderate in magnitude) over 108 months on the episodic memory composite, and a learning deficit (large in magnitude) over 6 days on the ORCA-LLT. Alzheimer{\textquoteright}s disease (AD)–related cognitive abnormalities can manifest before preclinical AD thresholds.",
keywords = "Alzheimer{\textquoteright}s disease, Amyloid, Apolipoprotein E, Learning, Memory",
author = "Lim, {Yen Ying} and Baker, {Jenalle E.} and Andrea Mills and Loren Bruns and Christopher Fowler and Jurgen Fripp and Rainey-Smith, {Stephanie R.} and David Ames and Masters, {Colin L.} and Paul Maruff",
note = "Funding Information: YYL reports grants from the National Health and Medical Research Council (GNT1111603, GNT1147465). Funding for the ORCA study was provided by the Dementia Australia Research Foundation and the Victorian Medical Research Acceleration Fund. Funding Information: Funding for the AIBL study was provided in part by the study partners (Australian Commonwealth Scientific Industrial and Research Organization [CSIRO], Edith Cowan University [ECU], Mental Health Research Institute [MHRI], Alzheimer{\textquoteright}s Australia [AA], National Ageing Research Institute [NARI], Austin Health, CogState Ltd., Hollywood Private Hospital, Sir Charles Gardner Hospital). The study also received support from the National Health and Medical Research Council (NHMRC) and the Dementia Collaborative Research Centres program (DCRC2), as well as ongoing funding from the Science and Industry Endowment Fund (SIEF). Funding Information: Alzheimer{\textquoteright}s Australia (Victoria and Western Australia) assisted with promotion of the AIBL study and the screening of telephone calls from volunteers. We acknowledge the financial support of the Cooperative Research Centre (CRC) for Mental Health. The CRC program is an Australian Government Initiative. We thank all those who participated in the study for their commitment and dedication to helping advance research into the early detection and causation of AD. Publisher Copyright: {\textcopyright} 2020 The Authors. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
doi = "10.1002/dad2.12136",
language = "English",
volume = "13",
journal = "Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring",
issn = "2352-8729",
publisher = "John Wiley & Sons",
number = "1",
}
