Apolipoprotein E and Change in Episodic Memory in Blacks and Whites

Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Ill., USA.
Neuroepidemiology (Impact Factor: 2.48). 01/2013; 40(3):211-219. DOI: 10.1159/000342778
Source: PubMed

ABSTRACT Background: Apolipoprotein E (APOE) ε4 is related to faster decline in episodic memory in Whites, but the relation is unknown in Blacks. The purpose of this study was to determine whether ε4 has a selective effect on decline in episodic memory in Blacks. Methods: Data are from two cohort studies with similar design. The sample consisted of 1,211 participants [28.4% Blacks, mean age = 78.6 years (SD = 7.4), education = 14.7 years (SD = 3.1)] without dementia at baseline, who underwent annual clinical evaluations for up to 6 years. Summary measures of 5 cognitive abilities were derived from 18 neuropsychological tests. Results: In mixed models that controlled for age, sex, education, and race, possession of ε4 (present in 32.9% of Blacks and 21.0% of Whites, p < 0.001) was related to faster decline in episodic memory and 4 other cognitive abilities (all p values <0.01). In separate models that examined the interaction of race and ε4 on decline, there was no significant difference between Blacks and Whites in the effect of ε4 on decline in episodic memory, perceptual speed, or visuospatial ability. By contrast, the effect of ε4 differed for semantic memory and working memory. Results were similar after adjusting for vascular conditions. Conclusions: The results suggest that APOE ε4 is related to a faster rate of decline in episodic memory in Blacks similar to Whites. In addition, there were racial differences in the effect of ε4 in other cognitive abilities such that the ε4 allele was related to faster decline in semantic memory and working memory for Whites but not for Blacks.

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    ABSTRACT: Research shows that lipid levels may be associated with cognitive function, particularly among women. We aimed to examine total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), high-density lipoprotein (HDL), and HDL/LDL ratio in relation to cognitive performance, measured with six well-established cognitive domains and a composite cognitive score (CCS). In this cross-sectional study, biomarkers and neuropsychological assessment were available for 141 adults with MMSE scores ≥ 24 (mean age = 69 years, 47% female, mean education = 14.4 years) attending a neuropsychological evaluation. Ordinary least squares regressions were adjusted for age, gender, education, and depressive symptoms in Model 1 and also for apolipoprotein E4 (APOE4) status in Model 2. High-density lipoprotein cholesterol (HDL-C) was associated with better CCS (β = 0.24; p = 0.014). This association was significant among women (β = 0.30; p = 0.026) and not among men (β = 0.20; p = 0.124). HDL-C was also related to attention/working memory (β = 0.24; p = 0.021), again only among women (β = 0.37; p = 0.012) and not men (β = 0.15; p = 0.271). Adjusting for APOE4 yielded significance for high HDL-C and CCS (β = 0.24; p = 0.022). HDL-C was the main lipoprotein affecting cognitive function, with results somewhat more pronounced among women. Research should investigate the possibility of finding ways to boost HDL-C levels to potentially promote cognitive function.
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    ABSTRACT: We aimed to evaluate the combined effects of HIV and APOE ε4 allele(s) on glial metabolite levels, and on known cognitive deficits associated with either condition, across the ages.METHODS: One hundred seventy-seven participants, primarily of white and mixed race (97 seronegative subjects: aged 44.7 ± 1.3 years, 85 [87.6%] men, 28 [28.9%] APOE ε4+; 80 HIV+ subjects: aged 47.3 ± 1.1 years, 73 [91.3%] men, 23 [28.8%] APOE ε4+), were assessed cross-sectionally for metabolite concentrations using proton magnetic resonance spectroscopy in 4 brain regions and for neuropsychological performance.RESULTS: Frontal white matter myo-inositol was elevated in subjects with HIV across the age span but showed age-dependent increase in seronegative subjects, especially in APOE ε4+ carriers. In contrast, only seronegative APOE ε4+ subjects showed elevated myo-inositol in parietal cortex. All APOE ε4+ subjects had lower total creatine in basal ganglia. While all HIV subjects showed greater cognitive deficits, HIV+ APOE ε4+ subjects had the poorest executive function, fluency memory, and attention/working memory. Higher myo-inositol levels were associated with poorer fine motor function across all subjects, slower speed of information processing in APOE ε4+ subjects, and worse fluency in HIV+ APOE ε4+ subjects.CONCLUSIONS: In frontal white matter of subjects with HIV, the persistent elevation and lack of normal age-dependent increase in myo-inositol suggest that persistent glial activation attenuated the typical antagonistic pleiotropic effects of APOE ε4 on neuroinflammation. APOE ε4 negatively affects energy metabolism in brain regions rich in dopaminergic synapses. The combined effects of HIV infection and APOE ε4 may lead to greater cognitive deficits, especially in those with greater neuroinflammation. APOE ε4 allele(s) may be a useful genetic marker to identify white and mixed-race HIV subjects at risk for cognitive decline.
    Neurology 05/2014; 82(24). DOI:10.1212/WNL.0000000000000526 · 8.30 Impact Factor
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    ABSTRACT: Objective To determine whether a polygenic risk score for Alzheimer's disease (AD) predicts dementia probability and memory functioning in non-Hispanic black (NHB) and non-Hispanic white (NHW) participants from a sample not used in previous genome-wide association studies.Methods Non-Hispanic white and NHB Health and Retirement Study (HRS) participants provided genetic information and either a composite memory score (n = 10,401) or a dementia probability score (n = 7690). Dementia probability score was estimated for participants' age 65+ from 2006 to 2010, while memory score was available for participants age 50+. We calculated AD genetic risk scores (AD-GRS) based on 10 polymorphisms confirmed to predict AD, weighting alleles by beta coefficients reported in AlzGene meta-analyses. We used pooled logistic regression to estimate the association of the AD-GRS with dementia probability and generalized linear models to estimate its effect on memory score.ResultsEach 0.10 unit change in the AD-GRS was associated with larger relative effects on dementia among NHW aged 65+ (OR = 2.22; 95% CI: 1.79, 2.74; P < 0.001) than NHB (OR=1.33; 95% CI: 1.00, 1.77; P = 0.047), although additive effect estimates were similar. Each 0.10 unit change in the AD-GRS was associated with a −0.07 (95% CI: −0.09, −0.06; P < 0.001) SD difference in memory score among NHW aged 50+, but no significant differences among NHB (β = −0.01; 95% CI: −0.03, 0.02; P = 0.546). The estimated effect of the GRS was significantly smaller among NHB than NHW (P < 0.05) for both outcomes.Conclusion This analysis provides evidence for differential relative effects of the GRS on dementia probability and memory score among NHW and NHB in a new, national data set.
    09/2014; 4(5). DOI:10.1002/brb3.248


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