Learning deficit in cognitively normal apoe ε4 carriers with low β-amyloid

• Published in: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
• Main Authors: Lim, Yen Ying, Baker, Jenalle E., Mills, Andrea, Bruns, Loren, Fowler, Christopher, Fripp, Jurgen, Rainey-Smith, Stephanie R., Ames, David, Masters, Colin L., Maruff, Paul
• Format: Text
• Language: unknown
• Published: Edith Cowan University, Research Online, Perth, Western Australia 2021
• Subjects: Alzheimer’s disease; Amyloid; Apolipoprotein E; Learning; Memory; Medicine and Health Sciences; Orca
• Online Access: https://ro.ecu.edu.au/ecuworkspost2013/10419; https://ro.ecu.edu.au/cgi/viewcontent.cgi?article=11425&context=ecuworkspost2013

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’s disease (AD)–related cognitive abnormalities can manifest before preclinical AD thresholds.