Frontiers in Aging Neuroscience Aging Neuroscience

Abstract

but not in young participants. However, negative results have been reported as well (Potter et al., 2009), and the impact of COMT genotype on cognition is still a matter of debate (Barnett et al., 2008; Goldman et al., 2009). Potential interactions between genetic phenotype and environmental factors have been suggested that render neurons more or less vulnerable to aging processes and neurodegenerative changes (Mattson et al., 2004b; Lindenberger et al., 2008). For example, COMT genotype has been linked with the inter-individual cogni-tive response to extrinsic manipulation: Cognitive performance, in this case working memory, was found to be improved in Val/ Val-carriers after pharmacologically induced dopamine release by oral amphetamine administration, whereas performance in Met/ Met-carriers was decreased at high working memory load (Mattay et al., 2003). This genotype–drug interaction was also evident in functional magnetic resonance imaging (fMRI) during working memory tasks in the same study, where Val/Val-carriers showed a more efficient activation after amphetamine administration, which was similar to the activation seen in Met/Met-carriers after placebo , and vice versa (Mattay et al., 2003). Similarly, when using a behavioral manipulation, Loughead et al. (2009) could demonstrate