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

Lim, Y.Y., Baker, J.E., Mills, A., Bruns, L., Fowler, C., Fripp, J., Rainey‐Smith, S.R., Ames, D., Masters, C.L. and Maruff, P. (2021) Learning deficit in cognitively normal APOE ε4 carriers with LOW β‐amyloid. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, 13 (1). Art. e12136.

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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.


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.


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).


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.

Item Type: Journal Article
Publisher: Elsevier Inc. on behalf of the Alzheimer’s Association
Copyright: © 2020 The Authors.
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