Microglial activation is inversely associated with cognition in individuals living with HIV on effective antiretroviral therapy

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Objective:Despite viral suppression, HIV-associated cognitive impairment persists and may be partially due to persistent immune signalling by cells of the myeloid-lineage. Here, we aimed to understand the contribution of activated microglia located in vulnerable brain regions (e.g. frontal, subcortical) of HIV-infected, virally suppressed (HIV+VS) individuals in relation to cognitive and motor function.Design:Twenty-one HIV+VS individuals underwent PET with [11C]DPA-713 to image the translocator protein 18 kDa (TSPO), a marker of microglial activation, and completed a comprehensive neuropsychological test battery.Methods:Multivariable linear regressions were used to examine the contribution of [11C]DPA-713 binding to cognitive performance.Results:Higher [11C]DPA-713 binding was associated with lower cognition among HIV+VS individuals. [11C]DPA-713 binding in middle frontal gyrus/frontal cortex, hippocampus/temporal cortex and occipital cortex was inversely associated with performance on a number of cognitive domains, including verbal memory, processing speed/attention/concentration, executive function, working memory and motor function. [11C]DPA-713 binding in parietal cortex, cerebellum and thalamus was associated with only specific cognitive domains including visual construction and verbal memory. Binding was not associated with global cognitive performance.Conclusion:The findings add to the growing body of evidence that immune-mediated brain injury may contribute to domain specific, HIV-associated, cognitive vulnerabilities despite viral suppression.

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