Biomarkers.

Area of Science:

• Neuroscience
• Metabolomics
• Public Health

Background:

• Socioeconomic factors such as income and employment significantly affect cognitive function, particularly declarative memory, in women living with HIV (WWH).
• Adverse social exposures may drive cognitive decline through intricate biological pathways.
• High-throughput metabolomics and causal mediation analysis were employed to investigate these biosocial links.

Purpose of the Study:

• To identify biological pathways mediating the relationship between socioeconomic status and cognitive trajectories in women.
• To explore the role of specific metabolites in linking income and employment to verbal learning and memory.

Main Methods:

• Utilized data from 324 women (225 WWH) in the Women's Interagency HIV Study, including biennial cognitive testing (Hopkins Verbal Learning Test-R) from 2009 onwards.
• Conducted serum metabolomic profiling using liquid chromatography tandem mass spectrometry.
• Employed multivariable generalized estimating equations, linear mixed-effects models, and regression-based multiple mediation analyses to assess metabolite associations and mediation effects, with a 5% false discovery rate.

Main Results:

• Identified 16 metabolites associated with verbal memory and 15 with verbal learning trajectories, with key metabolites including serotonin, taurine, and adenosine.
• Found that 30% of employment's effect and 18.2% of income's effect on verbal learning were mediated by metabolite levels.
• Determined that 35.6% of employment's effect and 25.4% of income's effect on verbal memory were mediated by altered metabolomic profiles.

Conclusions:

• Health determinants significantly influence biological processes involved in cognitive decline.
• Altered metabolomic signatures are key mediators linking socioeconomic factors to cognitive function in women.
• Biosocial interventions are crucial to mitigate the impact of social conditions on cognitive health.