Abstract
Aging is associated with deficits in several cognitive domains as well as a decline in brain dopamine activity. Catechol-O-methyl transferase (COMT), an enzyme involved in the degradation of dopamine, is a critical determinant of the availability of this neurotransmitter in the prefrontal cortex. A functional single nucleotide polymorphism in the COMT gene, Val158Met, modulates the activity of this enzyme and affects cognition and the brain regions underlying this function. The effects of COMT Val158Met polymorphism are magnified in the aging brain. Here, we review the evidence supporting a role of COMT genetic variation in cognitive as well as structural and functional brain changes associated with senescence. We will address the potential modulatory role of genetic and non-genetic factors on the neural and cognitive effects of COMT Val158Met in late life. Furthermore, we will discuss the viability of a COMT-targeted treatment for improving cognitive efficiency in aging.
Keywords: Catechol-O-methyl transferase, dopamine, aging, cognition, catechol-O-methyl transferase inhibitors, COMT Inhibitors, COMT, Working memory, functional magnetic resonance imaging, Dopamine transporter, val158Met, BDNF-Met, ACE Inhibitors
CNS & Neurological Disorders - Drug Targets
Title:Catechol-O-Methyl Transferase Modulates Cognition in Late Life: Evidence and Implications for Cognitive Enhancement
Volume: 11 Issue: 3
Author(s): Fabio Sambataro, Maria Pennuto and Robert Christian Wolf
Affiliation:
Keywords: Catechol-O-methyl transferase, dopamine, aging, cognition, catechol-O-methyl transferase inhibitors, COMT Inhibitors, COMT, Working memory, functional magnetic resonance imaging, Dopamine transporter, val158Met, BDNF-Met, ACE Inhibitors
Abstract: Aging is associated with deficits in several cognitive domains as well as a decline in brain dopamine activity. Catechol-O-methyl transferase (COMT), an enzyme involved in the degradation of dopamine, is a critical determinant of the availability of this neurotransmitter in the prefrontal cortex. A functional single nucleotide polymorphism in the COMT gene, Val158Met, modulates the activity of this enzyme and affects cognition and the brain regions underlying this function. The effects of COMT Val158Met polymorphism are magnified in the aging brain. Here, we review the evidence supporting a role of COMT genetic variation in cognitive as well as structural and functional brain changes associated with senescence. We will address the potential modulatory role of genetic and non-genetic factors on the neural and cognitive effects of COMT Val158Met in late life. Furthermore, we will discuss the viability of a COMT-targeted treatment for improving cognitive efficiency in aging.
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Sambataro Fabio, Pennuto Maria and Christian Wolf Robert, Catechol-O-Methyl Transferase Modulates Cognition in Late Life: Evidence and Implications for Cognitive Enhancement, CNS & Neurological Disorders - Drug Targets 2012; 11 (3) . https://dx.doi.org/10.2174/187152712800672463
DOI https://dx.doi.org/10.2174/187152712800672463 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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