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- W1973428080 abstract "In many populations, a significant association has been observed between Apolipoprotein E (APOE) genotype and risk of AD. The role of APOE has recently been expanded to include cognitive decline however this relationship has not been defined in African Americans. To further characterize the role of APOE on cognitive decline in African Americans, twelve single nucleotide polymorphisms (SNPs) located throughout the gene were genotyped in 1500 subjects. In addition, thirteen SNPs within the phosphodiesterase 4D gene (PDE4D) that showed association with ischemic stroke in an Icelandic population were analyzed. Demented and cognitively impaired subjects at baseline were eliminated. Mixed effects models were run separately to test the effect of the interaction between each SNP and time since baseline with individual cognitive scores over time as measured by the Community Screening Instrument for Dementia. The models were adjusted for the individual SNP, time since baseline, age, gender, years of education, and interactions between time with gender, years of education and age. P-values were adjusted using the Bonferroni adjustment for multiple comparisons. The APOE ϵ4 SNP (rs429358) was significantly associated with cognitive decline (p=0.0001). Two other SNPs (rs434132: p=0.0142 and rs7259620: p=0.0001) located upstream were also associated with decline in cognitive function. Only one PDE4D SNP (rs3909458) was significant for cognitive decline (p = 0.0208). This SNP was the most distal of the thirteen that were genotyped. Interestingly, two SNPs upstream of the promoter region of APOE showed significant association with cognitive decline in African Americans. This may be due to the level of heterozygosity of the markers, the proximate location of the markers to the ϵ4 SNP or may confer some functional relevance to the region. One SNP within PDE4D showed association with cognitive decline. PDE4D is a relatively large gene and several additional SNPs would need to be genotyped and analyzed to pursue the validity of this initial association. However, since this gene was originally associated with stroke, it may be useful in teasing out different causes of cognitive decline." @default.
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- W1973428080 date "2008-07-01" @default.
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- W1973428080 title "P3-289: Apolipoprotein E and phosphodiesterase 4D variants associated with cognitive decline in elderly African-Americans" @default.
- W1973428080 doi "https://doi.org/10.1016/j.jalz.2008.05.1857" @default.
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