We investigated the relationship between cerebrospinal fluid (CSF) and plasma biomarkers of inflammation, neurodegeneration, and neurocognitive performance in people with HIV (PWH), using longitudinal Show more
We investigated the relationship between cerebrospinal fluid (CSF) and plasma biomarkers of inflammation, neurodegeneration, and neurocognitive performance in people with HIV (PWH), using longitudinal samples from two previously published cohorts: ACTG A5090 (virally suppressed on antiretroviral therapy, ART) and A736 (ART-naïve or failing). We analyzed paired CSF and plasma samples, as well as 7-domain standardized neurocognitive test scores, at baseline and 24 weeks. Biomarkers included markers of inflammation (e.g., TNF-α, IL-6, IP-10) and neurodegeneration (e.g., NFL, p-Tau217, Aβ42), which were quantified via high-sensitivity immunoassays. Associations with cognition were tested using regression, mediation, and interaction models. Cross-sectional analyses revealed nominal associations between inflammatory markers and cognitive performance, with plasma IL-6 and IP-10 at baseline, and CSF TNFα at week 24 showing the strongest correlations (p < 0.05, uncorrected); however, none survived correction for multiple comparisons. Conversely, higher CSF Aβ42 and plasma BDNF were positively associated with memory and executive function. Longitudinally, biomarker changes did not significantly predict change in global cognition (ΔNPZ-8); the strongest trend (p-Tau217, ρ = -0.12, p = 0.38) was not statistically significant, and multivariate models failed to identify robust predictors (R These results suggest a potential role of CSF TNFα in mediating the neurocognitive effects of HIV and highlight compartment-specific inflammatory dynamics. Plasma TNFα, GFAP, and NFL may serve as peripheral indicators of CNS pathology, though with only moderate concordance. Astrocyte-tau interactions require cautious interpretation pending replication in larger cohorts. Show less
Exercise and heat stress have been reported to independently provide benefits to brain health. We tested the hypothesis that 8 weeks of post-exercise local heating, passive local heating only, or exer Show more
Exercise and heat stress have been reported to independently provide benefits to brain health. We tested the hypothesis that 8 weeks of post-exercise local heating, passive local heating only, or exercise training only improves cognitive performance compared to a control group. Sixty young, healthy participants (n = 30 female, age: 23 [3] years) were randomised into one of four groups: control (CON), aerobic exercise (EX), local heating (HEAT), or combined heat and exercise (HEATEX). Participants completed supervised sessions three times per week for 8 weeks. Exercise sessions were completed at 70-75% of maximum heart rate on a cycle ergometer, and local heating sessions involved hot water immersion (42°C) of the feet (both 45 min duration). The HEATEX group performed both the EX and HEAT components sequentially in the same session (90 min total duration). Cognitive performance was measured at baseline and at the end of the 8-week intervention using the digit symbol substitution task (DSST) and the Stroop test. There was a main effect of time (P < 0.001) where DSST performance improved; however, there was no group effect (P = 0.089) or time by group interaction (P = 0.119). There was no effect of the interventions on Stroop cost (baseline: 90 [SD: 70] ms; post-intervention: 84 [SD: 70] ms; time by condition interaction P = 0.205). Similarly, there were no effects of the interventions on circulating plasma concentrations of brain-derived neurotrophic factor (interaction P = 0.189). Eight weeks of exercise training and/or local heating is not sufficient to improve cognitive performance in young, moderately fit individuals. Show less