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

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.

Abstract

Background.  Dyslipidemia and apolipoprotein E4 ( APOE ϵ4) allele are risk factors for age-related cognitive decline, but how these risks are modified by human immunodeficiency virus (HIV) infection is unclear.

Methods.  In a longitudinal nested study from the Multicenter AIDS Cohort Study, 273 HIV type 1–infected (HIV ⁺) men aged 50–65 years with baseline HIV RNA <400 copies/mL and on continuous antiretroviral therapy (ART) in ≥95% of follow-up visits were matched by sociodemographic variables to 516 HIV-uninfected (HIV ^–) controls. The association between lipid markers (total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides), APOE genotype, and cognitive decline in HIV infection was examined using mixed-effects models.

Results.  The median baseline age of participants was 51, 81% were white, and 89% had education >12 years. HIV ⁺ men had similar baseline total cholesterol and LDL-C, but lower HDL-C and higher triglycerides than controls ( P < .001). Higher total cholesterol and LDL-C were associated with faster rates of cognitive decline ( P < .01), whereas higher HDL-C attenuated decline ( P = .02) in HIV ⁺ men. In HIV ⁺ men with elevated cholesterol, statin use was associated with a slower estimated rate of decline ( P = .02). APOE ϵ4 genotype accelerated cognitive decline in HIV ⁺ but not HIV ^– men ( P = .01), with trajectories diverging from HIV ^– ε4 carriers after age 50. Total cholesterol levels did not modify the association of ϵ4 genotype with decline ( P = .9).

Conclusions.  Elevated cholesterol and APOE ϵ4 genotype are independent risk factors for cognitive decline in ART-adherent HIV ⁺ men aged >50 years. Treatment of dyslipidemia may be an effective strategy to reduce cognitive decline in older HIV ⁺ individuals.