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

Introduction In cognitively normal (CN) adults, increased rates of amyloid beta (Aβ) accumulation can be detected in low Aβ (Aβ-) apolipoprotein E (APOE) e4 carriers. We aimed to determine the effect of e4 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- e4 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- e4 carriers compared to non-carriers (d = 1.2). Discussion In Aβ- CNs, e4 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.