NEUROLOGY 2010;74:1296-1302
© 2010 American Academy of Neurology
COMT genotype and cognitive function
An 8-year longitudinal study in white and black elders
A.J. Fiocco, PhD,
K. Lindquist, MS,
R. Ferrell, MD,
R. Li, MD,
E.M. Simonsick, PhD,
M. Nalls, PhD,
T.B. Harris, MD,
K. Yaffe, MD For the Health ABC Study
From the Departments of Psychiatry (A.J.F., K.Y.), Epidemiology and Biostatistics (K.Y.), Neurology (K.Y.), and Medicine (K.L.), School of Medicine, University of California, San Francisco; San Francisco Veterans Affairs Medical Center (K.Y.), San Francisco, CA; Department of Human Genetics (R.F.), Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA; Department of Preventive Medicine (R.L.), University of Tennessee Health Science Center, Memphis; Clinical Research Branch (E.M.S.), National Institute on Aging, Baltimore, MD; Laboratory of Neurogenetics (M.N.) and Laboratory of Epidemiology, Demography, and Biometry, Intramural Research Program (T.B.H.), National Institute on Aging, Bethesda, MD.
Address correspondence and reprint requests to Dr. Alexandra J. Fiocco, University of California, San Francisco, 4150 Clement St., Box 116H, San Francisco, CA 94121 afiocco{at}klaru-baycrest.on.ca
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 (val158met) 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]).
Conclusion: These findings suggest that the Val allele has a protective impact on cognitive decline in late life.
Abbreviations: 3MS = Modified Mini-Mental State Examination; BMI = body mass index; CES-D = Center for Epidemiologic Studies–Depression Scale; COMT = catechol-O-methyltransferase; DSST = Digit Symbol Substitution Test; Health ABC = Health Aging and Body Composition; PFC = prefrontal cortex.
Study funding: Funded by N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106. The measurement of F2-isoprostane was funded by 1R21DK068608-01A2. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. Dr. Fiocco is supported by the Canadian Institute of Health Research Fellowship in the area of Longitudinal Study on Aging. Dr. Yaffe was supported in part by AG031155 and an anonymous foundation.
Disclosure: Author disclosures are provided at the end of the article.
Received November 2, 2009. Accepted in final form February 3, 2010.
