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: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2021
• Subjects: Orca
• Online Access: http://dx.doi.org/10.1002/dad2.12136; https://onlinelibrary.wiley.com/doi/pdf/10.1002/dad2.12136; https://onlinelibrary.wiley.com/doi/full-xml/10.1002/dad2.12136

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