Yaffe K, Kanaya A M, Lindquist K, Hsueh W C, Cummings S R, Beamer B, Newman A, Rosano C, Li R, Harris T
Department of Psychiatry and Neurology, University of California, San Francisco, CA 94121, United States.
Neurobiol Aging. 2008 Jan;29(1):78-83. doi: 10.1016/j.neurobiolaging.2006.09.010. Epub 2006 Oct 18.
The Pro12Ala polymorphism of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) 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.
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 > or = 5 points).
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.
The PPAR-gamma Ala12 allele carriers may have less risk of developing cognitive decline.
过氧化物酶体增殖物激活受体γ（PPAR-γ）的Pro12Ala多态性与糖尿病和肥胖风险降低相关，而这两种疾病均与认知障碍有关。我们测试了这种多态性是否与认知相关。
2961名参与者（平均年龄74.1岁；41%为黑人；52%为女性）在基线和4年随访时接受了改良简易精神状态检查（3MS）和数字符号替换测验（DSST）。测试分数针对年龄、性别、教育程度、脑血管疾病、抑郁和载脂蛋白E基因型进行了调整，另外还针对种族进行了调整。我们确定了Ala等位基因与认知功能下降（3MS下降≥5分）之间的关联。
在基线时，Ala携带者在两项认知测试中的未调整分数均高于非携带者（3MS，94.2对92.5，p<0.001；DSST，40.2对34.5，p<0.001）。同样，Ala携带者的随访分数也更高。多变量调整导致了类似的结果；对种族进行额外调整减弱了基线3MS结果。4年后，17.5%的Ala携带者出现认知功能下降，而非携带者中这一比例为25%（未调整的比值比=0.61；95%置信区间，0.4-0.82；调整后的比值比=0.75；95%置信区间，0.55-1.02）。对包括空腹血糖和血脂水平在内的代谢变量进行进一步调整并未改变结果。
PPAR-γ Ala12等位基因携带者发生认知功能下降的风险可能较低。
