title: Lipid Profiles and APOE4 Allele Impact Midlife Cognitive Decline in HIV-Infected Men on Antiretroviral Therapy.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute.|Department of Neurology, Massachusetts General Hospital, Boston.
authors.forename: Shibani S
authors.initials: SS
authors.lastname: Mukerji
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Boston.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Locascio
authors.affiliation: Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute.
authors.forename: Vikas
authors.initials: V
authors.lastname: Misra
authors.affiliation: Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute.
authors.forename: David R
authors.initials: DR
authors.lastname: Lorenz
authors.affiliation: Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute.
authors.forename: Alex
authors.initials: A
authors.lastname: Holman
authors.affiliation: Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute.
authors.forename: Anupriya
authors.initials: A
authors.lastname: Dutta
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Penugonda
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Wolinsky
authors.affiliation: Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute.
authors.forename: Dana
authors.initials: D
authors.lastname: Gabuzda
mesh_terms: D000367:Age Factors; D000368:Aged; D000483:Alleles; D023241:Antiretroviral Therapy, Highly Active; D053327:Apolipoprotein E4 / Q000235:genetics*; D015415:Biomarkers; D060825:Cognitive Dysfunction / Q000097:blood* / Q000175:diagnosis / Q000209:etiology*; D004198:Disease Susceptibility; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D008055:Lipids / Q000097:blood*; D008297:Male; D000073216:Mental Status and Dementia Tests; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D053327:Apolipoprotein E4; D015415:Biomarkers; D008055:Lipids
keywords: APOE; HIV-1; aging; cholesterol; cognitive decline