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COMT genotype and cognitive function: an 8-year longitudinal study in white and black elders.

ABSTRACT: 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.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.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]).These findings suggest that the Val allele has a protective impact on cognitive decline in late life.

SUBMITTER: Fiocco AJ

PROVIDER: S-EPMC2860484 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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COMT genotype and cognitive function: an 8-year longitudinal study in white and black elders.

Fiocco A J AJ Lindquist K K Ferrell R R Li R R Simonsick E M EM Nalls M M Harris T B TB Yaffe K K

Neurology 20100401 16

<h4>Objective</h4>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.<h4>Methods</h4>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 ba ...[more]

PMID: 20404311

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Project description:BackgroundAlbuminuria, a kidney marker of microvascular disease, may herald microvascular disease elsewhere, including in the brain.Study designCross sectional.Setting & participantsBoston, MA, elders receiving home health services to maintain independent living who consented to brain magnetic resonance imaging.PredictorUrine albumin-creatinine ratio (ACR).OutcomePerformance on a cognitive battery assessing executive function and memory by using principal components analysis and white matter hyperintensity volume on brain imaging, evaluated in logistic and linear regression models.ResultsIn 335 participants, mean age was 73.4 +/- 8.1 years and 123 participants had microalbuminuria or macroalbuminuria. Each doubling of ACR was associated with worse executive function (beta = -0.05; P = 0.005 in univariate and beta = -0.07; P = 0.004 in multivariable analyses controlling for age, sex, race, education, diabetes, cardiovascular disease, hypertension, medications, and estimated glomerular filtration rate [eGFR]), but not with worse memory or working memory. Individuals with microalbuminuria or macroalbuminuria were more likely to be in the lower versus the highest tertile of executive functioning (odds ratio, 1.18; 95% confidence interval, 1.06 to 1.32; odds ratio, 1.19; 95% confidence interval, 1.05 to 1.35 per doubling of ACR in univariate and multivariable analyses, respectively). Albuminuria was associated with qualitative white matter hyperintensity grade (odds ratio, 1.13; 95% confidence interval, 1.02 to 1.25; odds ratio, 1.15; 95% confidence interval, 1.02 to 1.29 per doubling of ACR) in univariate and multivariable analyses and with quantitative white matter hyperintensity volume (beta = 0.11; P = 0.007; beta = 0.10; P = 0.01) in univariate and multivariable analyses of log-transformed data. Results were similar when excluding individuals with macroalbuminuria.LimitationsSingle measurement of ACR, indirect creatinine calibration, and reliance on participant recall for elements of medical history.ConclusionsAlbuminuria is associated with worse cognitive performance, particularly in executive functioning, as well as increased white matter hyperintensity volume. Albuminuria likely identifies greater brain microvascular disease burden.

Project description:ObjectiveTo determine whether variants in the estrogen receptors 1 (alpha) and 2 (beta) (ESR1 and ESR2) genes are associated with cognitive impairment in non-demented elderly men and women.BackgroundSeveral single nucleotide polymorphisms (SNPs) on ESR1 and ESR2 genes have been associated with a range of hormone sensitive diseases such as breast cancer and osteoporosis. Genetic variations in ESR may also influence cognitive aging but are less studied, especially among men.MethodsWe studied 2527 participants enrolled in an ongoing prospective study of community-dwelling elders. Four SNPs from ESR1 and four from ESR2 were analyzed. We measured cognitive function with the Modified Mini-Mental Status Examination (3MS) at baseline and biannually; cognitive impairment was defined as a decline of five or more points over 4 years. We calculated odds of developing cognitive impairment across SNPs using gender-stratified logistic regression and adjusted analyses for age, education, baseline 3MS score and in addition for race.ResultsOne thousand three hundred and forty-three women (mean age 73.4) and 1184 men (mean age 73.7) comprised our cohort. Among women, after multivariate adjustment, two of the ESR1 SNPs (rs8179176, rs9340799) and two of the ESR2 SNPs (rs1256065, rs1256030) were associated with likelihood of developing cognitive impairment, although the association for rs8179176 was of trend level significance. In men, one of the ESR1 SNPs (rs728524) and two of the ESR2 (rs1255998, rs1256030) were associated with cognitive impairment. Further adjustment for race attenuated the results somewhat. There was no association between any ESR SNP and level of bioavailable estradiol but testosterone level did vary among two of the SNPs (p<0.05).ConclusionWe found that among non-demented community elders, several SNPs in the ESR1 and ESR2 genes were associated with risk of developing cognitive impairment. These findings suggest that estrogen receptor genetic variants may play a role in cognitive aging.

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COMT genotype and cognitive function: an 8-year longitudinal study in white and black elders.

Publications

COMT genotype and cognitive function: an 8-year longitudinal study in white and black elders.

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