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

Abstract

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.

Keywords

• Alzheimer's disease
• amyloid
• apolipoprotein E
• learning
• memory