Positive effects of cholinergic stimulation favor young APOE ε4 carriers
Résumé
The potential of putative cognitive-enhancing compounds to improve mental processing both in healthy and vulnerable populations is an area of growing interest to scientific and clinical communities. The possible influence of individual genetic differences on efficacy of these compounds has yet to be considered. We sought to investigate the profile of young-adult apolipoprotein E (APOE) ε4 carriers across cognitive domains given that possession of this gene variant increases risk of developing dementia in later life. We also explored whether APOE genotype interacts with the cognitive enhancer, nicotine. 1mg of the cholinergic agonist nicotine was administered via nasal spray to healthy non-smoking young adults (aged 18-30) with either ε3/ε3 (N = 29) or ε4 (at least one ε4 allele, N = 27) genotype. Participants were matched on age, sex and IQ, in a placebo controlled, double blind 2 (drug: placebo, nicotine) x 2 (genotype: ε3, ε4) between subjects design. Here we demonstrate that, paradoxically, possession of the ε4 allele confers a cognitive advantage on tasks mediated by the frontal lobe, and that young carriers of the ε4 allele show larger cognitive benefit from procholinergic nicotinic stimulation. These results are the first to demonstrate that genetic differences influence the efficacy of a cognitive enhancer.
Origine : Fichiers produits par l'(les) auteur(s)