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

AIDS. 2018 Jul 31;32(12):1661-1667. doi: 10.1097/QAD.0000000000001858.

Abstract

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. [C]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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Dementia Complex / pathology*
  • Adult
  • Anti-Retroviral Agents / therapeutic use*
  • Female
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV Infections / pathology*
  • Humans
  • Male
  • Microglia / pathology*
  • Middle Aged
  • Neuropsychological Tests
  • Positron-Emission Tomography
  • Receptors, GABA / analysis

Substances

  • Anti-Retroviral Agents
  • Receptors, GABA
  • TSPO protein, human