Positive effects of cholinergic stimulation favor young APOE epsilon4 carriers.

Marchant, Natalie L, King, Sarah L, Tabet, Naji and Rusted, Jennifer M (2010) Positive effects of cholinergic stimulation favor young APOE epsilon4 carriers. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 35 (5). pp. 1090-6. ISSN 1740-634X

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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) varepsilon4 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 varepsilon3/varepsilon3 (N=29) or varepsilon4 (at least one varepsilon4 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: varepsilon3, varepsilon4) between subjects design. Here, we show that, paradoxically, possession of the varepsilon4 allele confers a cognitive advantage on tasks mediated by the frontal lobe, and that young carriers of the varepsilon4 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: Brighton and Sussex Medical School > Neuroscience
School of Psychology > Psychology
Subjects: R Medicine
R Medicine > RC Internal medicine > RC0321 Neurosciences. Biological psychiatry. Neuropsychiatry
Depositing User: Tracey O'Gorman
Date Deposited: 12 Nov 2012 09:41
Last Modified: 04 Aug 2017 17:13
URI: http://sro.sussex.ac.uk/id/eprint/42001
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