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Distinct associations of peripheral mtDNA copy number and bioenergetic function with cognition in women with HIV and psychiatric comorbidities
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AIDS Aug 2026
Download the PDF here
Download the PDF here
Discussion
This study provides evidence that distinct peripheral mitochondrial markers are differentially associated with cognitive performance in virally suppressed WWH with cognitive impairment. Whereas mtDNAcn showed only modest and domain-specific associations with cognition, mitochondrial bioenergetic function demonstrated strong relationships with both verbal and working memory performance. Specifically, increased mitochondrial proton leak was associated with poorer verbal recall, verbal recognition, and working memory. In addition, higher mtDNAcn was associated with reduced maximum respiration and spare respiratory capacity, suggesting a complex relationship between mitochondrial content and functional capacity in WWH. Together, these findings suggest that mitochondrial genomic content and mitochondrial bioenergetic function capture different aspects of mitochondrial health and may relate differently to cognitive outcomes in WWH.
Mitochondrial functional measures demonstrated the strongest relationships with cognition in this study. Greater mitochondrial proton leak was associated with poorer verbal and working memory performance, particularly delayed verbal recall and recognition as well as poorer working memory. Proton leak reflects reduced efficiency of the mitochondrial electron transport chain and is often considered an indicator of mitochondrial dysfunction. Increased proton leak can arise from oxidative damage to mitochondrial membranes which disrupt the proton gradient required for ATP production.
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