Cohen, Jacqueline
(2019)
Relationship between cognition and statin use by genotype at APOE and three proinflammatory cytokine loci in the Long Life Family Study.
Master Essay, University of Pittsburgh.
Abstract
In the United States, greater than one-third of adults over the age of 40 years are using cholesterol lowering medication, and 90% of these medications are statins. The relationship between statin use and cognition is unclear: some studies report that statin use is associated with cognitive impairment, whereas other studies report that statins may have a protective effect against cognitive decline. Because cardiovascular disease and Alzheimer’s Disease (AD) are major public health issues, knowledge of the effects of statin use on AD is critical. In this study, I investigated the relationship between measures of cognition and statin use, as well as the interaction effect of statin use and genotype at APOE and three proinflammatory cytokine loci (IL1B, IL6, and TNF⍺), by analyzing data from the Long Life Family Study (LLFS) comprising of 1691 probands and their siblings (mean age=90yo), their 2439 offspring (mean age=61yo) and 808 spouses of the offspring (mean age=61yo). Cognitive outcome was measured by two quantitative and four verbal cognitive traits, as well as the Mini-Mental State Exam (MMSE) (in the proband generation only). Each generation was examined separately. Statin use was 16% among probands and 11% among offspring. As expected, mean cognitive scores for all measures were lower among probands than among offspring. Before adjusting for covariates, the study results showed significantly higher scores in probands taking statins for 3/7 cognitive traits (p≤0.005) and lower scores in offspring taking statins for 3/6 cognitive traits (p<0.02). After adjustment for age, sex, and education, statin use was only associated with cognitive measures digit forward in probands/siblings (p=0.038) and vegetable recall in offspring/spouses (p=0.001). Few significant genetic effects on cognition were seen, except IL6-174 in the probands/siblings and TNFɑ-308 SNP in the offspring/spouses with digit backward (p≤0.05), and IL6-174 and IL1B-31 by statin use interaction with animal recall in the probands/siblings (p<0.05). The above indicate additional studies on individuals with early stages of AD are needed. Because APOE is a significant risk factor in both cardiovascular disease and AD, additional pharmacological and pharmacogenetic studies of the effects of statins, particularly among APOE ε4/ε4 homozygotes, are warranted.
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