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ToolsSacripante, Riccardo, James, Tabitha, Hornberger, Michael, Blake, Joshua and Renoult, Louis (2025) Semantic memory in healthy Apolipoprotein ε4 carriers: A systematic review. Cortex. ISSN 0010-9452 (In Press)
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Abstract
The Apolipoprotein epsilon 4 (APOE ε4) genetic variant is notoriously linked to enhanced risk of developing Alzheimer’s Disease (AD). Several studies have examined how this allele could influence cognitive functioning in healthy adults, and whether ε4 carriers show a subtle cognitive decline that would indicate preclinical AD pathology. Research has predominantly focused on episodic memory, where ε4 carriers are usually impaired, while semantic memory functioning has received less attention. To evaluate current evidence on the influence of APOE ε4 on semantic memory, we systematically reviewed the research literature assessing semantic memory in non-clinical adult populations according to the PRISMA guidelines. We reviewed 17 studies that revealed high heterogeneity in how semantic memory is conceptualised and assessed. When tested via standard neuropsychological tests (i.e., category fluency, naming, language comprehension, and general knowledge), ε4 carriers did not significantly differ from non-carriers. Instead, ε4 carriers showed lower performance than non-carriers when assessed via more complex semantic memory tasks (i.e., longer category fluency tasks, autobiographical memory tasks, measures of semantic clustering). The impact of APOE ε4 on semantic memory thus appears to be restricted to these more complex tasks, which could constitute a better match to episodic memory tasks for which APOE effects are typically observed, though a mediating role of executive functions should also be considered. Future research investigating autobiographical memory retrieval in ε4 carriers could provide a more sensitive and ecologically valid assessment of semantic memory and would help disentangle personal and general forms of semantic memory.
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