PPAR-γ Pro12Ala genotype and risk of cognitive decline in elders

Yaffe, K.; Kanaya, A.M.; Lindquist, K.; Hsueh, W.C.; Cummings, S.R.; Beamer, B.; Newman, A.; Rosano, C.; Li, R.; Harris, T.; for the Health ABC Study,

doi:10.1016/j.neurobiolaging.2006.09.010

« Previous Next »Neurobiology of Aging
Volume 29, Issue 1 , Pages 78-83, January 2008

PPAR-γ Pro12Ala genotype and risk of cognitive decline in elders

K. Yaffe
- Department of Psychiatry and Neurology, University of California, San Francisco, CA, United States
- Department of Epidemiology, University of California, San Francisco, CA, United States
- San Francisco VA Medical Center, San Francisco, CA, United States
- Corresponding author at: c/o University of California, San Francisco, P.O. Box 181, 4150 Clement Street, San Francisco, CA 94121, United States. Tel.: +1 415 221 4810; fax: +1 415 750 6641.
A.M. Kanaya
- Department of Epidemiology, University of California, San Francisco, CA, United States
- Department of Medicine, University of California, San Francisco, CA, United States
K. Lindquist
- Department of Geriatrics, University of California, San Francisco, CA, United States
W.C. Hsueh
- Department of Medicine, University of California, San Francisco, CA, United States
S.R. Cummings
- California Pacific Medical Center, San Francisco, CA, United States
B. Beamer
- Department of Medicine, Johns Hopkins University, Baltimore, MD, United States
A. Newman
- Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, United States
C. Rosano
- Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, United States
R. Li
- Center for Genomics and Bioinformatics, Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, United States
T. Harris
- Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, MD, United States
for the Health ABC Study

Received 15 May 2006; received in revised form 3 August 2006; accepted 13 September 2006. published online 20 October 2006.

Abstract

Background

The Pro12Ala polymorphism of peroxisome proliferator-activated receptor-gamma (PPAR-γ) has been associated with decreased risk of diabetes and obesity, both disorders linked to cognitive impairment. We tested whether this polymorphism is associated with cognition.

Methods

Two thousand nine hundred sixty-one participants (mean age, 74.1; 41% Black; 52% women) were administered the Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) at baseline and 4 year follow-up. Test scores were adjusted for age, sex, education, cerebrovascular disease, depression and APOE genotype and additionally for race. We determined the association between Ala allele and development of cognitive decline (3MS decline of ≥5 points).

Results

At baseline, unadjusted scores on both cognitive tests were higher for Ala carriers compared to non-carriers (3MS, 94.2 versus 92.5, p<0.001; DSST, 40.2 versus 34.5, p<0.001). Similarly, follow-up scores were higher for Ala carriers. Multivariable adjustment led to similar results; additional adjustment for race attenuated the baseline 3MS results. After 4 years, 17.5% of Ala carriers developed cognitive decline compared to 25% among non-carriers (unadjusted OR=0.61; 95%CI, 0.46–0.82; adjusted OR=0.75; 95%CI, 0.55–1.02). Further adjustment for metabolic variables including fasting blood glucose and lipid level did not change the results.