TY - JOUR
T1 - Microglial activation is inversely associated with cognition in individuals living with HIV on effective antiretroviral therapy
AU - Rubin, Leah H.
AU - Sacktor, Ned
AU - Creighton, Jason
AU - Du, Yong
AU - Endres, Christopher J.
AU - Pomper, Martin G.
AU - Coughlin, Jennifer M.
N1 - Funding Information:
This research was supported by NIH 5R21MH082277, NIH 5R01MH092443, NIH R01EB012547, NIH 5T32EB006351, NIEHS ES007062, Lupus Foundation of America, Alexander Wilson Schweizer Fellowship (JC) and NFL Charities.
Funding Information:
We acknowledge NIH 5R21MH082277, NIH 5R01MH092443, NIH R01EB012547, NIEHS ES007062, NIH 5T32EB006351, the Lupus Foundation for America, the AlexanderWilson Schweizer Fellowship (JC) and NFL Charities for financial support.We are also grateful to the Johns Hopkins PET Center for provision of the radiotracer. This research was supported by NIH 5R21MH082277, NIH 5R01MH092443, NIH R01EB012547, NIH 5T32EB006351, NIEHS ES007062, Lupus Foundation of America, Alexander Wilson Schweizer Fellowship (JC) and NFL Charities.
Funding Information:
We acknowledge NIH 5R21MH082277, NIH 5R01MH092443, NIH R01EB012547, NIEHS ES007062, NIH 5T32EB006351, the Lupus Foundation for America, the Alexander Wilson Schweizer Fellowship (JC) and NFL Charities for financial support. We are also grateful to the Johns Hopkins PET Center for provision of the radiotracer.
Publisher Copyright:
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2018
Y1 - 2018
N2 - Objective: Despite viral suppression, HIV-associated cognitive impairment persists and may be partially due to persistent immune signalling by cells of the myeloidlineage. 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.
AB - Objective: Despite viral suppression, HIV-associated cognitive impairment persists and may be partially due to persistent immune signalling by cells of the myeloidlineage. 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.
KW - Cognition
KW - HIV
KW - Neuroinflammation
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U2 - 10.1097/QAD.0000000000001858
DO - 10.1097/QAD.0000000000001858
M3 - Article
C2 - 29746297
AN - SCOPUS:85056552101
SN - 0269-9370
VL - 32
SP - 1661
EP - 1667
JO - AIDS
JF - AIDS
IS - 12
ER -