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Glucocorticoid Receptor Function and Cognitive Performance in Women With HIV.
Leah H Rubin1, Mandakh Bekhbat, Susie Turkson
1From the Department of Neurology and Psychiatry (Rubin), Johns Hopkins University School of Medicine; Department of Epidemiology (Rubin, Springer, Gange), Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland; Emory University School of Medicine (Bekhbat); Department of Biostatistics and Bioinformatics, Rollins School of Public Health (Mehta), Emory University, Atlanta, Georgia; Department of Psychiatry, Psychology and Obstetrics & Gynecology (Maki), University of Illinois at Chicago, Chicago, Illinois; Departments of Medicine, Epidemiology & Population Health, and Obstetrics & Gynecology and Women's Health (Anastos), Albert Einstein College of Medicine, Bronx; Department of Neurology (Gustafson), SUNY-Downstate Health Sciences University, Brooklyn, New York; Department of Medicine (Spence), Georgetown University, Washington, DC; Institute for Health Promotion and Disease Prevention Research (Milam), University of Southern California, Los Angeles; Weill Institute for Neurosciences, Department of Neurology, and Division of Infectious Diseases (Chow), University of California, San Francisco, San Francisco, California; The Core Center, Bureau of Health Services of Cook County (Weber), Chicago, Illinois; and Department of Anatomy and Neurobiology, School of Medicine (Neigh), Virginia Commonwealth University, Richmond, Virginia.
Glucocorticoid receptor (GCR) function alterations may impact cognition in older adults with HIV. This study found that HIV status and age may alter GCR downstream effects, potentially via epigenetic changes in target genes.
Area of Science:
- Neuroscience
- Immunology
- Endocrinology
Background:
- Alterations in glucocorticoid receptor (GCR) function are implicated as a risk factor for cognitive decline in aging populations, particularly among individuals with human immunodeficiency virus (HIV).
- Understanding how HIV serostatus and age interact to influence GCR function and its association with cognitive performance is crucial for identifying at-risk individuals and developing targeted interventions.
Purpose of the Study:
- To investigate whether HIV serostatus and age modify the relationship between GCR function and cognitive performance in women.
- To explore the association between HIV status, age, and GCR function, and to examine potential moderating effects on cognition.
Main Methods:
- Eighty women with HIV and 80 HIV-uninfected women, stratified by age (younger and older groups), were recruited from the Women's Interagency HIV Study.
- Participants underwent comprehensive neuropsychological testing, and peripheral blood mononuclear cells were analyzed for GCR function.
- Multivariable linear regression models were used to assess associations and interactions between HIV serostatus, age, GCR function, and cognitive outcomes.
Main Results:
- Among older women with HIV, higher FKBP5 expression was linked to poorer attention/working memory, an association not observed in HIV-uninfected women.
- No significant interactions were found between HIV serostatus and age regarding dexamethasone-stimulated gene expression or inflammatory markers.
- HIV serostatus was associated with differential expression of GCR target genes PER1 and DUSP1 following dexamethasone stimulation.
Conclusions:
- HIV serostatus and age may modulate the downstream effects of GCR function, even if receptor engagement remains similar.
- These modifications in GCR downstream influence could potentially be mediated by epigenetic alterations in GCR target genes.
- The findings highlight the complex interplay between HIV, aging, and the neuroendocrine system in cognitive health.
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