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Short-term memory in middle-aged individuals with different APOE alleles was examined using a recently developed task which is sensitive to medial temporal lobe (MTL) damage. Individuals (age-range: 40-51 years) with ε3/ε3, ε3/ε4 and ε4/ε4 APOE genotypes (N = 60) performed a delayed estimation task with a sensitive continuous measure of report. The paradigm allowed us to measure memory for items and their locations, as well as maintenance of identity-location feature binding in memory. There was a significant gene-dosage dependent effect of the ε4 allele on performance: memory decay or forgetting was slower in ε4 carriers, as measured by localization error and after controlling for misbinding errors. Furthermore ε4 carriers made less misbinding errors. These findings were specific to male carriers only. Thus, male ε4 carriers are at a behavioral advantage in midlife on a sensitive task of short-term memory. The results would be consistent with an antagonistic pleiotropy hypothesis and hightight the interaction of gender on the influence of APOE in cognition.

Original publication




Journal article


Cortex; a journal devoted to the study of the nervous system and behavior

Publication Date





98 - 105


Oxford Centre for Human Brain Activity, Department of Psychiatry, University of Oxford, Oxford, UK; Department of Experimental Psychology, University of Oxford, Oxford, UK. Electronic address:


Humans, Alzheimer Disease, Memory, Short-Term, Neuropsychological Tests, Sex Factors, Genotype, Heterozygote, Alleles, Adult, Middle Aged, Female, Male, Apolipoprotein E4