Dataset Information

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

ABSTRACT: BACKGROUND:Dyslipidemia and apolipoprotein E4 (APOE ?4) 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 ?4 genotype accelerated cognitive decline in HIV(+) but not HIV(-) men (P = .01), with trajectories diverging from HIV(-) ?4 carriers after age 50. Total cholesterol levels did not modify the association of ?4 genotype with decline (P = .9). CONCLUSIONS:Elevated cholesterol and APOE ?4 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.

SUBMITTER: Mukerji SS

PROVIDER: S-EPMC5036920 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Mukerji Shibani S SS Locascio Joseph J JJ Misra Vikas V Lorenz David R DR Holman Alex A Dutta Anupriya A Penugonda Sudhir S Wolinsky Steven M SM Gabuzda Dana D

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20160722 8

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 27448678

Similar Datasets

Project description:The ability to detect preclinical Alzheimer's disease is of great importance, as this stage of the Alzheimer's continuum is believed to provide a key window for intervention and prevention. As Alzheimer's disease is characterized by multiple pathological changes, a biomarker panel reflecting co-occurring pathology will likely be most useful for early detection. Towards this end, 175 late middle-aged participants (mean age 55.9 ± 5.7 years at first cognitive assessment, 70% female) were recruited from two longitudinally followed cohorts to undergo magnetic resonance imaging and lumbar puncture. Cluster analysis was used to group individuals based on biomarkers of amyloid pathology (cerebrospinal fluid amyloid-?42/amyloid-?40 assay levels), magnetic resonance imaging-derived measures of neurodegeneration/atrophy (cerebrospinal fluid-to-brain volume ratio, and hippocampal volume), neurofibrillary tangles (cerebrospinal fluid phosphorylated tau181 assay levels), and a brain-based marker of vascular risk (total white matter hyperintensity lesion volume). Four biomarker clusters emerged consistent with preclinical features of (i) Alzheimer's disease; (ii) mixed Alzheimer's disease and vascular aetiology; (iii) suspected non-Alzheimer's disease aetiology; and (iv) healthy ageing. Cognitive decline was then analysed between clusters using longitudinal assessments of episodic memory, semantic memory, executive function, and global cognitive function with linear mixed effects modelling. Cluster 1 exhibited a higher intercept and greater rates of decline on tests of episodic memory. Cluster 2 had a lower intercept on a test of semantic memory and both Cluster 2 and Cluster 3 had steeper rates of decline on a test of global cognition. Additional analyses on Cluster 3, which had the smallest hippocampal volume, suggest that its biomarker profile is more likely due to hippocampal vulnerability and not to detectable specific volume loss exceeding the rate of normal ageing. Our results demonstrate that pathology, as indicated by biomarkers, in a preclinical timeframe is related to patterns of longitudinal cognitive decline. Such biomarker patterns may be useful for identifying at-risk populations to recruit for clinical trials.

Project description:In epidemiologic studies, human immunodeficiency virus (HIV)-infected men on antiretroviral therapy (ART) are at higher risk of incident diabetes mellitus compared with women with similar treatment histories. We used metabolomics to determine whether a sex difference in plasma amino acids, acylcarnitines, and organic acids predictive of diabetes and impaired energy metabolism is present in HIV-infected persons on long-term ART.We enrolled 70 HIV-infected adults (43% women) on efavirenz, tenofovir, and emtricitabine (Atripla) with HIV-1 RNA <50?copies/mL for over 2 years. Half of the HIV-infected subjects were obese, and these were matched with 30 obese HIV-negative controls. All subjects had no history of diabetes, statin use, or heavy alcohol use. Fasting insulin sensitivity was measured using homeostatic model assessment 2 (HOMA2), and adipose tissue was measured using dual-energy x-ray absorptiometry (DEXA). Liquid chromatography/mass spectrometry was used to quantitate fasting plasma branched chain and aromatic amino acids predictive of incident diabetes, and C3 and C5 acylcarnitinines and organic acids indicative of impaired energy metabolism.HIV-infected women had more baseline risk factors for insulin resistance: women were older (46 vs 44 years) and had a longer ART duration (8.4 vs 5.1 years, P?<?0.05 for both) compared with men but had similar CD4+ count (median 701?cells/?L), smoking and hepatic C prevalence, and body mass index (BMI) (median 30.3?kg/m). However, women had higher insulin sensitivity compared with men (P?<?0.01), and lower plasma levels of isoleucine, leucine, valine, phenylalanine, and tyrosine (P?<?0.01 for all), and lower C3 and C5 acylcarnitines (P?<?0.01 for all), in multivariable regression models after adjusting for DEXA fat mass index, age, race, CD4+ count, smoking, and ART duration. In the obese HIV-infected subjects and HIV-negative controls, the relationship of sex and plasma metabolite levels did not significantly differ according to HIV-status.HIV-infected women on non-nucleoside reverse transcriptase inhibitor-based ART had superior glucose tolerance and lower plasma metabolites associated with the development of diabetes compared with men with similar metabolic disease risk profiles. The relationship between sex and plasma metabolite levels did not significantly differ according to HIV-status among obese subjects, suggesting the observed sex-differences may not be specific to HIV infection.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets