Does apolipoprotein E genotype influence cognition in middle-aged individuals?

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Purpose of review

The apolipoprotein ε4 (APOE ε4) allele has been recognized as a risk factor for the late-onset Alzheimer's disease. It may modulate cognitive performance in nondemented younger and older ε4 carriers. Does APOE ε4 genotype affect cognition in mid-aged population as well? In this review, a summary of current evidence concerning the effect of this genotype on cognition in middle-aged individuals will be presented.

Recent findings

Recent findings did not provide a clear cognitive signature of APOE ε4 genotype in mid-life. A positive, negative, and null effect on cognitive functions has been observed, especially on memory performance.


The discrepancy of the results may be because of several limitations. Future studies should be focused on a narrower participants’ age range and a wider level of education range. Moreover, cognition should be explored by means of more sensitive tasks. Finally, interaction between genotype and additional risk factors and other allelic variants should be taken into account to fully understand the APOE genotype effect on brain and cognition.

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