Learning deficit in cognitively normal APOE ε4 carriers with LOW β‐amyloid

• Published in: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
• Main Authors: Yen Ying Lim, Jenalle E. Baker, Andrea Mills, Loren Bruns Jr, Christopher Fowler, Jurgen Fripp, Stephanie R. Rainey‐Smith, David Ames, Colin L Masters, Paul Maruff
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2021
• Subjects: Alzheimer's disease; amyloid; apolipoprotein E; learning; memory; Neurology. Diseases of the nervous system; RC346-429; Geriatrics; RC952-954.6; Orca
• Online Access: https://doi.org/10.1002/dad2.12136; https://doaj.org/article/29e1c02bde994115af43b8750883003a

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.