COMT genotype and cognitive function: an 8-year longitudinal study in white and black elders.
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.
Fiocco
A J
AJ
Department of Psychiatry, School of Medicine, University of California, San Francisco, CA 94121, USA. afiocco@klaru-baycrest.on.ca
Lindquist
K
K
Ferrell
R
R
Li
R
R
Simonsick
E M
EM
Nalls
M
M
Harris
T B
TB
Yaffe
K
K
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
D005819:Genetic Markers; D002394:Catechol O-Methyltransferase; D014633:Valine; D004298:Dopamine
Proc Natl Acad Sci U S A. 2003 May 13;100(10):6186-91
12716966
Biol Psychiatry. 2005 Dec 1;58(11):901-7
16043133
Metabolism. 2008 May;57(5):708-11
18442637
Am J Hum Genet. 2007 Apr;80(4):716-26
17357077
J Health Psychol. 2005 Nov;10(6):739-52
16176953
J Gerontol. 1981 Sep;36(5):591-7
7264244
Am J Hum Genet. 1998 Dec;63(6):1839-51
9837836
J Am Geriatr Soc. 2007 Feb;55(2):259-64
17302664
Neuropsychol Dev Cogn B Aging Neuropsychol Cogn. 2004 Jun;11(2-3):304-24
16755303
Biol Psychiatry. 1999 Aug 15;46(4):557-67
10459407
Neurology. 2008 Sep 30;71(14):1057-64
18367704
Arch Neurol. 1995 May;52(5):477-84
7733842
Science. 2006 Dec 22;314(5807):1930-3
17185601
Arch Neurol. 1987 Jul;44(7):720-2
3593061
BMC Neurosci. 2009 Sep 30;10:125
19793392
J Neurosci. 2007 Sep 19;27(38):10196-209
17881525
J Cogn Neurosci. 2005 Jul;17(7):1018-25
16102234
Neurosci Biobehav Rev. 2006;30(6):791-807
16901542
Front Hum Neurosci. 2008 Sep 23;2:11
18958211
Behav Genet. 2004 Sep;34(5):533-9
15319576
Biol Psychiatry. 2009 Sep 15;66(6):540-8
19539269
J Clin Epidemiol. 2003 Jul;56(7):622-8
12921930
Biol Psychiatry. 1999 Aug 1;46(3):312-28
10435197
J Neural Transm (Vienna). 2004 Apr;111(4):547-67
15057524
Neurosci Lett. 2007 Jun 21;421(1):57-61
17548151
Am J Hum Genet. 2004 Nov;75(5):807-21
15457404
Neuroimage. 2006 Oct 1;32(4):1722-32
16884927
Neurosci Lett. 2006 Dec 6;409(3):205-9
17029783
J Gerontol B Psychol Sci Soc Sci. 2002 Jul;57(4):S247-56
12084794
Nat Rev Neurosci. 2004 Feb;5(2):87-96
14735112
Neuroimage. 2007 Oct 1;37(4):1437-44
17689985
Neuropsychopharmacology. 2007 May;32(5):1011-20
17063156
Curr Alzheimer Res. 2007 Apr;4(2):103-9
17430231
Genetics. 2000 Jun;155(2):945-59
10835412
J Clin Psychiatry. 1987 Aug;48(8):314-8
3611032
Arch Neurol. 2009 Mar;66(3):324-8
19273750
Arch Neurol. 2009 Mar;66(3):329-35
19273751