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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