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Lipid Profiles and APOE4 Allele Impact Midlife Cognitive Decline in HIV-Infected Men on Antiretroviral Therapy

View Article: PubMed Central - PubMed

ABSTRACT

Elevated cholesterol and APOE ε4 genotype were independent risk factors for cognitive decline in antiretroviral therapy–adherent human immunodeficiency virus (HIV)-infected men aged 50–65 years, whereas higher high-density lipoprotein attenuated cognitive decline. Treatment of dyslipidemia may reduce midlife cognitive decline among HIV-infected individuals.

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Related in: MedlinePlus

APOEϵ4 allele and total cholesterol have independent effects on cognitive decline in antiretroviral therapy–treated human immunodeficiency virus–infected (HIV+) men. The distribution of APOE genotypes among HIV+ and human immunodeficiency virus–uninfected (HIV–) subjects (A), and estimated slopes for cognitive scores for APOEϵ4 allele and HIV infection status (B) are shown. Cognitive scores for subjects with unknown or ϵ2/ϵ2 genotypes are shown in gray (B). Among those with ϵ4 genotype, cognitive decline for HIV+ϵ4 carriers (C) and noncarriers (D) modified by total cholesterol are shown. The annual rate of decline is estimated for a man with baseline age 50 years, and cohort mean IQ score 108, baseline Center for Epidemiological Studies Depression Scale score 9, and CD4 count held at 800 cells/mL. APOEϵ4 carriers had lower baseline cognitive scores than noncarriers (P = .03), an association that was not modified by HIV infection (P = .14). HIV+APOEϵ4 carriers showed accelerated decline in cognitive scores between ages 50 and 65 years, and the rate of accelerated decline was faster than predicted for HIV+ noncarriers (P = .01). Elevated total cholesterol levels were associated with faster rates of decline among HIV+ϵ4 noncarriers (P < 0.01), while the accelerated rate of decline in HIV+ϵ4 carriers was not further modified by cholesterol (P = .9).
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CIW495F3: APOEϵ4 allele and total cholesterol have independent effects on cognitive decline in antiretroviral therapy–treated human immunodeficiency virus–infected (HIV+) men. The distribution of APOE genotypes among HIV+ and human immunodeficiency virus–uninfected (HIV–) subjects (A), and estimated slopes for cognitive scores for APOEϵ4 allele and HIV infection status (B) are shown. Cognitive scores for subjects with unknown or ϵ2/ϵ2 genotypes are shown in gray (B). Among those with ϵ4 genotype, cognitive decline for HIV+ϵ4 carriers (C) and noncarriers (D) modified by total cholesterol are shown. The annual rate of decline is estimated for a man with baseline age 50 years, and cohort mean IQ score 108, baseline Center for Epidemiological Studies Depression Scale score 9, and CD4 count held at 800 cells/mL. APOEϵ4 carriers had lower baseline cognitive scores than noncarriers (P = .03), an association that was not modified by HIV infection (P = .14). HIV+APOEϵ4 carriers showed accelerated decline in cognitive scores between ages 50 and 65 years, and the rate of accelerated decline was faster than predicted for HIV+ noncarriers (P = .01). Elevated total cholesterol levels were associated with faster rates of decline among HIV+ϵ4 noncarriers (P < 0.01), while the accelerated rate of decline in HIV+ϵ4 carriers was not further modified by cholesterol (P = .9).

Mentions: Cohort characteristics of APOEϵ4 carriers and noncarriers were similar to the larger study cohort (Supplementary Table 3), and ε4 genotype frequencies were comparable (Figure 3A). Among HIV+ϵ4 carriers vs noncarriers, there were no differences in median baseline CD4 count or ART medications used, but HIV+ϵ4 carriers had higher baseline triglyceride levels (P < .001). While longitudinal decline in cognitive scores was observed among all HIV+ individuals, the rate of decline accelerated among HIV+APOEϵ4 carriers (P = .01; Table 3). Divergent estimated slopes in Figure 3B illustrate that the estimated cognitive trajectory for HIV+ϵ4 carriers deviates rapidly from HIV+ϵ4 noncarriers and HIV– controls aged 50–65 years. Given that there were no significant differences in the intercept between HIV+ carriers and noncarriers at study entry (Supplementary Table 4), cognitive decline for HIV+ϵ4 carriers is expected to start after age 50. In post hoc analyses accelerated rate of decline in perceptual speed, but no other cognitive domains, was estimated for HIV+ϵ4 carriers (P = .03; Supplementary Table 4). Given that cholesterol levels and APOEϵ4 genotype were associated with cognitive decline in HIV+ men, we next examined whether these covariates interact to influence the rate of decline. The 3-way interaction term between HIV infection, cholesterol, and time (P = .002; Table 3) remained significant for cognitive decline among HIV+ϵ4 carriers. While accelerated rates of decline were estimated among HIV+APOEϵ4 carriers vs noncarriers (P < .01), the annual rate of decline among ϵ4 carriers was not further modified by cholesterol levels (P = .9; Figure 3C and 3D and Table 3). Thus, cholesterol levels and presence of the ϵ4 allele have independent effects on cognitive decline in HIV+ subjects, and do not substantially influence their respective associations.Table 3.


Lipid Profiles and APOE4 Allele Impact Midlife Cognitive Decline in HIV-Infected Men on Antiretroviral Therapy
APOEϵ4 allele and total cholesterol have independent effects on cognitive decline in antiretroviral therapy–treated human immunodeficiency virus–infected (HIV+) men. The distribution of APOE genotypes among HIV+ and human immunodeficiency virus–uninfected (HIV–) subjects (A), and estimated slopes for cognitive scores for APOEϵ4 allele and HIV infection status (B) are shown. Cognitive scores for subjects with unknown or ϵ2/ϵ2 genotypes are shown in gray (B). Among those with ϵ4 genotype, cognitive decline for HIV+ϵ4 carriers (C) and noncarriers (D) modified by total cholesterol are shown. The annual rate of decline is estimated for a man with baseline age 50 years, and cohort mean IQ score 108, baseline Center for Epidemiological Studies Depression Scale score 9, and CD4 count held at 800 cells/mL. APOEϵ4 carriers had lower baseline cognitive scores than noncarriers (P = .03), an association that was not modified by HIV infection (P = .14). HIV+APOEϵ4 carriers showed accelerated decline in cognitive scores between ages 50 and 65 years, and the rate of accelerated decline was faster than predicted for HIV+ noncarriers (P = .01). Elevated total cholesterol levels were associated with faster rates of decline among HIV+ϵ4 noncarriers (P < 0.01), while the accelerated rate of decline in HIV+ϵ4 carriers was not further modified by cholesterol (P = .9).
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CIW495F3: APOEϵ4 allele and total cholesterol have independent effects on cognitive decline in antiretroviral therapy–treated human immunodeficiency virus–infected (HIV+) men. The distribution of APOE genotypes among HIV+ and human immunodeficiency virus–uninfected (HIV–) subjects (A), and estimated slopes for cognitive scores for APOEϵ4 allele and HIV infection status (B) are shown. Cognitive scores for subjects with unknown or ϵ2/ϵ2 genotypes are shown in gray (B). Among those with ϵ4 genotype, cognitive decline for HIV+ϵ4 carriers (C) and noncarriers (D) modified by total cholesterol are shown. The annual rate of decline is estimated for a man with baseline age 50 years, and cohort mean IQ score 108, baseline Center for Epidemiological Studies Depression Scale score 9, and CD4 count held at 800 cells/mL. APOEϵ4 carriers had lower baseline cognitive scores than noncarriers (P = .03), an association that was not modified by HIV infection (P = .14). HIV+APOEϵ4 carriers showed accelerated decline in cognitive scores between ages 50 and 65 years, and the rate of accelerated decline was faster than predicted for HIV+ noncarriers (P = .01). Elevated total cholesterol levels were associated with faster rates of decline among HIV+ϵ4 noncarriers (P < 0.01), while the accelerated rate of decline in HIV+ϵ4 carriers was not further modified by cholesterol (P = .9).
Mentions: Cohort characteristics of APOEϵ4 carriers and noncarriers were similar to the larger study cohort (Supplementary Table 3), and ε4 genotype frequencies were comparable (Figure 3A). Among HIV+ϵ4 carriers vs noncarriers, there were no differences in median baseline CD4 count or ART medications used, but HIV+ϵ4 carriers had higher baseline triglyceride levels (P < .001). While longitudinal decline in cognitive scores was observed among all HIV+ individuals, the rate of decline accelerated among HIV+APOEϵ4 carriers (P = .01; Table 3). Divergent estimated slopes in Figure 3B illustrate that the estimated cognitive trajectory for HIV+ϵ4 carriers deviates rapidly from HIV+ϵ4 noncarriers and HIV– controls aged 50–65 years. Given that there were no significant differences in the intercept between HIV+ carriers and noncarriers at study entry (Supplementary Table 4), cognitive decline for HIV+ϵ4 carriers is expected to start after age 50. In post hoc analyses accelerated rate of decline in perceptual speed, but no other cognitive domains, was estimated for HIV+ϵ4 carriers (P = .03; Supplementary Table 4). Given that cholesterol levels and APOEϵ4 genotype were associated with cognitive decline in HIV+ men, we next examined whether these covariates interact to influence the rate of decline. The 3-way interaction term between HIV infection, cholesterol, and time (P = .002; Table 3) remained significant for cognitive decline among HIV+ϵ4 carriers. While accelerated rates of decline were estimated among HIV+APOEϵ4 carriers vs noncarriers (P < .01), the annual rate of decline among ϵ4 carriers was not further modified by cholesterol levels (P = .9; Figure 3C and 3D and Table 3). Thus, cholesterol levels and presence of the ϵ4 allele have independent effects on cognitive decline in HIV+ subjects, and do not substantially influence their respective associations.Table 3.

View Article: PubMed Central - PubMed

ABSTRACT

Elevated cholesterol and APOE &epsilon;4 genotype were independent risk factors for cognitive decline in antiretroviral therapy&ndash;adherent human immunodeficiency virus (HIV)-infected men aged 50&ndash;65 years, whereas higher high-density lipoprotein attenuated cognitive decline. Treatment of dyslipidemia may reduce midlife cognitive decline among HIV-infected individuals.

No MeSH data available.


Related in: MedlinePlus