ArticleNeuroImage2011
Impact of apolipoprotein E ε4 and HIV on cognition and brain atrophy: antagonistic pleiotropy and premature brain aging.
Article in NeuroImage, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 2 of them syntheses that pooled it.
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Who cites it
81 citing papers in PubMed, 2 syntheses or guidelines pooled it, 111 citations in OpenAlex.
- The impact of APOE ε4 on cognitive performance in adults with HIV: a systematic review and meta-analysis.AIDS (London, England) · 2026Pooled it
- HIV-associated executive dysfunction in the era of modern antiretroviral therapy: A systematic review and meta-analysis.Journal of clinical and experimental neuropsychology · 2018Pooled it
- Trial
- Adaptive working memory training improved brain function in human immunodeficiency virus-seropositive patients.Annals of neurology · 2017Trial
- Liposomal-Cannabidiol Nanoformulation to Suppress HIV Replication and Reduce Oxidative Stress in Infected Microglia.ACS biomaterials science & engineering · 2025Article
- Microglia and macrophages alterations in the CNS during acute SIV infection: A single-cell analysis in rhesus macaques.PLoS pathogens · 2024Article
- Neurocognitive profile in HIV subjects on INSTI-regimen- one year follow up: Is there room for optimism?PloS one · 2024Article
- Specificity and efficiency of tamoxifen-mediated Cre induction is equivalent regardless of age.iScience · 2023Article
- Independent and combined effects of methamphetamine use disorders and APOEε4 allele on cognitive performance and brain morphometry.Addiction (Abingdon, England) · 2023Article
- Apolipoprotein E and viral infection: Risks and Mechanisms.Molecular therapy. Nucleic acids · 2023Review
- Review
- Neurofunctional characteristics of executive control in older people with HIV infection: a comparison with Parkinson's disease.Brain imaging and behavior · 2022Article
- Prior Methamphetamine Use Disorder History Does Not Impair Interoceptive Processing of Soft Touch in HIV Infection.Viruses · 2021Article
- Current Considerations for Clinical Management and Care of People with HIV: Findings from the 11th Annual International HIV and Aging Workshop.AIDS research and human retroviruses · 2021Article
- Reductions in Gray Matter Linked to Epigenetic HIV-Associated Accelerated Aging.Cerebral cortex (New York, N.Y. : 1991) · 2021Article
- CAGE-seq reveals that HIV-1 latent infection does not trigger unique cellular responses in a Jurkat T cell model.Journal of virology · 2021Article
- Association of Immunosuppression and Viral Load With Subcortical Brain Volume in an International Sample of People Living With HIV.JAMA network open · 2021Article
- Apolipoprotein E Genetic Variation and Its Association With Cognitive Function in Rural-Dwelling Older South Africans.Frontiers in genetics · 2021Article
- Neurocognitive Impairment and Associated Genetic Aspects in HIV Infection.Current topics in behavioral neurosciences · 2021Article
- Transcriptomic and Genetic Profiling of HIV-Associated Neurocognitive Disorders.Frontiers in molecular biosciences · 2021Review
21 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveThe apolipoprotein E (APOE) ε4 allele may accelerate the progression of HIV disease, and increase the risk for developing HIV-associated neurocognitive disorder (HAND). Whether APOEε4 allele(s) and age may influence brain atrophy in HIV patients is unknown and was evaluated.
methodsAutomated morphometry on magnetic resonance images, using FreeSurfer analyses, neuropsychological testing and APOE genotyping were performed in 139 subjects [70 seronegative controls (SN); 69 clinically-stable HIV subjects].
resultsCompared to SN, HIV subjects had smaller volumes throughout the brain regardless of their HAND status. Compared to APOEε4- subjects, SN controls with APOEε4 had better memory and larger global brain volumes (cerebral white matter and cortex) while HIV subjects with the APOEε4 allele(s) had poorer cognition (verbal fluency, learning, executive function and memory) and smaller cerebral and cerebellar white matter and subcortical structures. Further stratification of age showed that younger (<50 years) APOEε4+SN subjects had larger putamen and cerebral white matter, while younger APOEε4+HIV subjects had poorer performance on verbal fluency and smaller brain volumes [3-way (HIV-status×APOEε4×Age) interaction-p-values=0.005 to 0.03].
interpretationThese findings suggest that APOEε4 allele(s) may show antagonistic pleiotropy on cognition and brain atrophy in SN controls, but may lead to premature aging with neurodegeneration in younger HIV patients prior to the development of HAND. Potential mechanisms for such interactions may include stronger neuro-inflammation or greater amyloid deposition in younger HIV subjects with APOEε4 allele(s). Early screening for the APOEε4 allele and brain atrophy with morphometry may guide neuroprotective intervention of cognitively normal HIV subjects prior to the development of HAND. Longitudinal follow-up studies and larger sample sizes are needed to validate these cross-sectional results.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.