title: Association study of a functional catechol-o-methyltransferase polymorphism and cognitive function in patients with dementia.
abstract: A functional catechol-o-methyltransferase (COMT Val158/108Met) polymorphism, a valine (Val) to methionine (Met) substitution, has been associated with cognitive processing in the normal brain, older age, mild cognitive impairment and in various dementias. COMT is involved in the breakdown of dopamine and other catecholamines, especially in the frontal cortex; hence the carriers of Met allele, with the lower enzymatic activity, are expected to perform better on particular neuro-cognitive tests. The study included 46 patients with dementia and 65 healthy older subjects. The neurological status was assessed, using the Mini Mental Status Examination (MMSE), and the batery of different neurological tests. In DNA samples COMT polymorphism was genotyped. Patients with dementia exhibited significant genotype-induced differences in scores for MMSE, Visual Association Test (VAT) duration of numbers test, VAT time of response to numbers test, VAT average response to numbers test and WPLCR/PPLR unanswered. Carriers of Met/Met genotype had significantly lower scores of MMSE, significantly longer time to respond to VAT duration of numbers test, VAT time of response to numbers test and VAT average response to numbers test, and significantly greater number of unanswered questions to WPLCR/PPLR when compared to Met/Val or Val/Val genotypes. Our preliminary data showed significantly impaired performance in several neuro-cognitive tests in carriers of Met/Met genotype in patients with dementia compared to either Met/Val or Val/Val genotype carriers. Although Met/Met genotype with more dopamine available in the frontal cortex should be associated with better neuro-cognitive test results than Met/Val or Val/Val genotype, our data on patients with dementia did not confirm this hypothesis. Further study on larger sample of patients is needed to clarify the role of COMT polymorphism in cognitive functions.
authors.affiliation: Rudjer BoSkovic Institute, Division of Molecular Medicine, Zagreb, Croatia.
authors.forename: Gordana
authors.initials: G
authors.lastname: Nedić
authors.forename: Fran
authors.initials: F
authors.lastname: Borovecki
authors.forename: Natasa
authors.initials: N
authors.lastname: Klepac
authors.forename: Zdenko
authors.initials: Z
authors.lastname: Mubrin
authors.forename: Sanja
authors.initials: S
authors.lastname: Hajnsek
authors.forename: Matea
authors.initials: M
authors.lastname: Nikolac
authors.forename: Dorotea
authors.initials: D
authors.lastname: Muck-Seler
authors.forename: Nela
authors.initials: N
authors.lastname: Pivac
mesh_terms: D000368:Aged; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003071:Cognition / Q000502:physiology*; D003704:Dementia / Q000201:enzymology / Q000235:genetics* / Q000523:psychology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic
chemical_list: D002394:Catechol O-Methyltransferase