title: COMT genotype and cognitive function: an 8-year longitudinal study in white and black elders.
abstract: OBJECTIVE
  Catechol-O-methyltransferase (COMT), an enzyme that catalyzes the degradation of dopamine, is necessary for cognitive function. Few studies have examined the prospective association between COMT (val(158)met) genotype and cognition in older adults.
  
  
  METHODS
  We assessed a biracial cohort of 2,858 elderly subjects without dementia who were followed for 8 years. The Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) were administered at baseline and years 3, 5, and 8. COMT by race, gender, and APOE status interactions were examined.
  
  
  RESULTS
  Stratified by race and adjusted for covariates, repeated-measures mixed-effects models showed no association between COMT genotype and baseline cognitive function in black or white subjects. In white subjects, COMT was associated with change in 3MS (Met/Met: -2.3 [0.60], Met/Val: -1.7 [0.40], and Val/Val: -1.2 [0.50]) and DSST (Met/Met: -5.60 [1.00], Met/Val: -4.80 [0.70], Val/Val: -4.00 [0.90]). In black subjects, COMT was associated with change in the DSST (Met/Met: -4.10 [2.1], Met/Val: -4.80 [0.90], Val/Val -2.60 [1.00]).
  
  
  CONCLUSIONS
  These findings suggest that the Val allele has a protective impact on cognitive decline in late life.
authors.affiliation: Department of Psychiatry, School of Medicine, University of California, San Francisco, CA 94121, USA. afiocco@klaru-baycrest.on.ca
authors.forename: A J
authors.initials: AJ
authors.lastname: Fiocco
authors.forename: K
authors.initials: K
authors.lastname: Lindquist
authors.forename: R
authors.initials: R
authors.lastname: Ferrell
authors.forename: R
authors.initials: R
authors.lastname: Li
authors.forename: E M
authors.initials: EM
authors.lastname: Simonsick
authors.forename: M
authors.initials: M
authors.lastname: Nalls
authors.forename: T B
authors.initials: TB
authors.lastname: Harris
authors.forename: K
authors.initials: K
authors.lastname: Yaffe
mesh_terms: D000367:Age Factors; D000368:Aged; D000375:Aging / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence / Q000235:genetics; D019943:Amino Acid Substitution / Q000235:genetics; D044383:Black People; D001923:Brain Chemistry / Q000235:genetics; D002394:Catechol O-Methyltransferase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D003072:Cognition Disorders / Q000201:enzymology* / Q000208:ethnology / Q000235:genetics*; D019610:Cytoprotection / Q000235:genetics; D004252:DNA Mutational Analysis; D003704:Dementia / Q000201:enzymology* / Q000208:ethnology / Q000235:genetics*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009483:Neuropsychological Tests; D044469:Racial Groups / Q000235:genetics; D013997:Time Factors; D014633:Valine / Q000235:genetics; D044465:White People
chemical_list: D005819:Genetic Markers; D002394:Catechol O-Methyltransferase; D014633:Valine; D004298:Dopamine
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