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

• Main Authors: Lim, Y.Y., Baker, J.E., Mills, A., Bruns, L., Fowler, C., Fripp, J., Rainey‐Smith, S.R., Ames, D., Masters, C.L., Maruff, P.
• Format: Article in Journal/Newspaper
• Language: English
• Published: Elsevier Inc. on behalf of the Alzheimer’s Association 2021
• Subjects: Orca
• Online Access: https://researchrepository.murdoch.edu.au/id/eprint/60667/

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.