Imaging the translocator protein 18 kDa within cognitive control and declarative memory circuits in virally-suppressed people with HIV.

IF 3.4 2区医学 Q3 IMMUNOLOGY AIDS Pub Date : 2024-10-11 DOI:10.1097/QAD.0000000000004034

Leah H Rubin, Pauline M Maki, Yong Du, Shannon Eileen Sweeney, Riley O'toole, Hwanhee Nam, Hannah Lee, Ana R Soule, Steven P Rowe, Wojciech G Lesniak, Il Minn, Raha Dastgheyb, Eran F Shorer, Katrina A Wugalter, Joan Severson, Yunkou Wu, Andrew W Hall, William B Mathews, Michael Kassiou, Robert F Dannals, Seble G Kassaye, Todd T Brown, Arnold Bakker, Martin G Pomper, Jennifer M Coughlin

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Abstract

Objectives: Virally-suppressed people with HIV (VS-PWH) show heterogeneity in patterns of cognitive dysfunction. To better understand the relationship between the neuroimmune response and cognition, we used positron emission tomography (PET) to image the translocator protein 18 kDa (TSPO). The study examined HIV-serostatus differences in TSPO as well as associations between regional TSPO and select cognitive processes defined using the Research Domain Criteria (RDoC) framework.

Design: Cross-sectional investigation in VS-PWH (n = 25) versus HIV-uninfected individuals (n = 18) of cognitive control and declarative memory, as well as [11C]DPA-713 PET measures of TSPO within cognitive control and declarative memory regions of interest.

Methods: Group differences in [11C]DPA-713 binding (VT) in cognitive control or declarative memory regions were examined using linear mixed models. Tests of associations between factor-derived cognitive system measures and PET measures were performed, controlling for TSPO genotype.

Results: There were no group differences in any of the four factor-derived cognitive system measures. VS-PWH had higher log [11C]DPA-713 VT across cognitive control regions(unstandardized beta coefficient reflecting mean difference [B] = 0.23, SE = 0.11, 95% confidence interval [CI] 0.01, 0.45, P = 0.04) and declarative memory regions (B = 0.24, SE = 0.11, 95%CI 0.02, 0.45, P = 0.03). Higher log [11C]DPA-713 VT in cognitive control regions related to poorer cognitive control in each group, and to worse self-reported cognitive performance in VS-PWH. Log [11C]DPA-713 VT in each declarative memory region did not associate with measured declarative memory.

Conclusions: A localized neuroimmune response marked by high TSPO in brain regions that subserve cognitive control may contribute to poorer cognitive control in VS-PWH.

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对病毒抑制型艾滋病病毒感染者认知控制和陈述性记忆回路中的转运蛋白 18 kDa 进行成像。

目的：病毒抑制型艾滋病病毒感染者（VS-PWH）的认知功能障碍模式具有异质性。为了更好地了解神经免疫反应与认知之间的关系，我们使用正电子发射断层扫描（PET）对转运体蛋白 18 kDa（TSPO）进行成像。该研究检测了 TSPO 的 HIV 血清学差异，以及区域 TSPO 与使用研究领域标准 (RDoC) 框架定义的特定认知过程之间的关联：设计：横断面调查 VS-PWH（n = 25）与 HIV 未感染者（n = 18）的认知控制和陈述性记忆，以及认知控制和陈述性记忆相关区域内 TSPO 的[11C]DPA-713 PET 测量：使用线性混合模型检验认知控制或陈述性记忆区域中[11C]DPA-713结合（VT）的组间差异。在控制 TSPO 基因型的情况下，对因子衍生认知系统测量和 PET 测量之间的关联进行了测试：结果：四个因子衍生认知系统测量结果均无组间差异。VS-PWH 在认知控制区域（反映平均差异的非标准化贝塔系数 [B] = 0.23，SE = 0.11，95% 置信区间 [CI] 0.01，0.45，P = 0.04）和陈述性记忆区域（B = 0.24，SE = 0.11，95%CI 0.02，0.45，P = 0.03）具有更高的对数[11C]DPA-713 VT。认知控制区域较高的对数[11C]DPA-713 VT与各组较差的认知控制有关，也与 VS-PWH 自我报告的认知表现较差有关。每个陈述性记忆区域的对数[11C]DPA-713 VT与测量的陈述性记忆无关：结论：认知控制脑区的高TSPO标记的局部神经免疫反应可能会导致VS-PWH患者的认知控制能力更差。

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来源期刊

AIDS 医学-病毒学

CiteScore

5.90

自引率

5.30%

发文量

478

审稿时长

3 months

期刊介绍： Publishing the very latest ground breaking research on HIV and AIDS. Read by all the top clinicians and researchers, AIDS has the highest impact of all AIDS-related journals. With 18 issues per year, AIDS guarantees the authoritative presentation of significant advances. The Editors, themselves noted international experts who know the demands of your work, are committed to making AIDS the most distinguished and innovative journal in the field. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool.