Catechol-O-Methyl Transferase Modulates Cognition in Late Life: Evidence and Implications for Cognitive Enhancement

Author(s): Fabio Sambataro, Maria Pennuto, Robert Christian Wolf.

Journal Name: CNS & Neurological Disorders - Drug Targets
(Formerly Current Drug Targets - CNS & Neurological Disorders)

Volume 11 , Issue 3 , 2012

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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

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Article Details

VOLUME: 11
ISSUE: 3
Year: 2012
Page: [195 - 208]
Pages: 14
DOI: 10.2174/187152712800672463
Price: $58

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