Discussion
Alzheimer’s dementia, anxiety, injury or neuronal dysfunction, HIV., neurotoxicity, HAND, visual anxiety stressors, AD
NEURODEGENERATIVE DISORDERS, PATHOPHYSIOLOGY, DISORDERS, SECONDARY, PATHOLOGY, PATHOGENESIS
The present study presents a secondary analysis of a large dataset of biomarkers analyzed from the blood/plasma and CSF during a 24-week randomized placebo-controlled clinical trial of patients with HAND. We conducted multiple biomarker comparisons, some of which are validated as biomarkers of HAND and others from Alzheimer’s dementia. We hypothesized that the AD biomarkers could help determine the effects of neuroprotective agents because of the similarities in the pathogenesis of HAND and AD. Plasma DA was significantly changed following treatment with lithium. The reduction in the plasma DA was also reduced in the placebo arm with a similar statistical significance of These findings could not support the neuroprotective benefits of lithium in moderate to severe HAND. Contrary, a previous study showed some evidence of lithium neuroprotection against HIV. In a small pilot study of PWH with HAND, lithium treatment for 10 weeks normalized neuronal metabolism and integrity (Schifitto et al. It is also relevant to note that despite the attempt to use a broader approach to neuropathogenesis, the selected biomarkers are not directly linked with the putative pathway of lithium mechanism of action except for BDNF. A reduction in the BDNF occurs in various neuropsychiatric disorders and neurodegenerative disorders (Benussi et al. Lithium response is associated with the Val66Met functional polymorphism of the BDNF gene located on chromosome 11p13 (Rybakowski Elevated DA results in activation of GSK-3-β, and lithium antagonizes this effect due to inhibition of GSK-3-β (Beaulieu et al. Unfortunately, we do not have serial blood pressure measurements to support our conjecture and the only study we know of that assessed a link between plasma catecholamine levels and anxiety and found no statistically significant changes used visual anxiety stressors (Gutierrrez-Martin et al. Because of the similarities between HAND and AD pathophysiology, we explored possible changes in the AD biomarkers at the end of the intervention (24 weeks). However, lithium did not change any of these biomarkers. In experimental animal models of AD, lithium's ability to prevent or reduce AD pathology has been demonstrated. Lithium was shown to reduce amyloid-beta synthesis in drosophila models of AD (Sofola-Adesakin et al. It is important to note that some of the biomarkers were within normal ranges, indicating no evidence of ongoing injury or neuronal dysfunction in both treatment arms. In addition, participants showed improvement in the GDS, likely secondary to the practice effect (Decloedt et al. In our study, over 80% of the participants were treated with non-nucleoside reverse transcriptase inhibitor-based ART regimens, mainly efavirenz (EFV). In vitro studies found that EFV and specifically its metabolite 8-hydroxy-EFV (8-OH-EFV) may cause neurotoxicity at therapeutic concentrations (Robertson et al. 