Positive Effects of Cholinergic Stimulation Favor Young APOE ε4 Carriers

Marchant, Natalie L, King, Sarah L, Tabet, Naji and Rusted, Jennifer M (2010) Positive Effects of Cholinergic Stimulation Favor Young APOE ε4 Carriers. Neuropsychopharmacology, 35 (5). pp. 1090-1096. ISSN 0893-133X

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Abstract

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) 4 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. A total of 1 mg of the cholinergic agonist nicotine was administered through nasal spray to healthy non-smoking young adults (aged 18-30) with either 3/3 (N29) or 4 (at least one 4 allele, N27) genotype. Participants were matched on age, sex, and IQ in a placebo-controlled, double-blind 2 (drug: placebo, nicotine) × 2 (genotype: 3, 4) between subjects design. Here, we show that, paradoxically, possession of the 4 allele confers a cognitive advantage on tasks mediated by the frontal lobe, and that young carriers of the 4 allele show larger cognitive benefit from procholinergic nicotinic stimulation. These results are the first to show that genetic differences influence the efficacy of a cognitive enhancer.

Item Type: Article
Schools and Departments: School of Psychology > Psychology
Subjects: B Philosophy. Psychology. Religion > BF Psychology
Depositing User: Natalie Marchant
Date Deposited: 06 Feb 2012 15:30
Last Modified: 26 Apr 2012 14:43
URI: http://sro.sussex.ac.uk/id/eprint/13024
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