Cognitive Dysfunction in Patients Treated with Androgen Deprivation Therapy: A Multimodality Functional Imaging Study to Evaluate Neuroinflammation.

IF 2.3 Q3 ONCOLOGY Prostate Cancer Pub Date : 2023-10-18 eCollection Date: 2023-01-01 DOI:10.1155/2023/6641707
Azeem Saleem, Syed Imran Ali Shah, Stephen A Mangar, Christopher Coello, Matthew B Wall, Gaia Rizzo, Terry Jones, Patricia M Price
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Abstract

Background: Androgen deprivation therapy (ADT) for prostate cancer is implicated as a possible cause of cognitive impairment (CI). CI in dementia and Alzheimer's disease is associated with neuroinflammation. In this study, we investigated a potential role of neuroinflammation in ADT-related CI.

Methods: Patients with prostate cancer on ADT for ≥3 months were categorized as having ADT-emergent CI or normal cognition (NC) based on self-report at interview. Neuroinflammation was evaluated using positron emission tomography (PET) with the translocator protein (TSPO) radioligand [11C]-PBR28. [11C]-PBR28 uptake in various brain regions was quantified as standardized uptake value (SUVR, normalized to cerebellum) and related to blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) choice-reaction time task (CRT) activation maps.

Results: Eleven patients underwent PET: four with reported CI (rCI), six with reported NC (rNC), and one status unrecorded. PET did not reveal any between-group differences in SUVR regionally or globally. There was no difference between groups on brain activation to the CRT. Regardless of the reported cognitive status, there was strong correlation between PET-TSPO signal and CRT activation in the hippocampus, amygdala, and medial cortex.

Conclusions: We found no difference in neuroinflammation measured by PET-TSPO between patients with rCI and rNC. However, we speculate that the strong correlation between TSPO uptake and BOLD-fMRI activation in brain regions involved in memory and known to have high androgen-receptor expression mediating plasticity (hippocampus and amygdala) might reflect inflammatory effects of ADT with compensatory upregulated/increased synaptic functions. Further studies of this imaging readout are warranted to investigate ADT-related CI.

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雄激素剥夺治疗患者的认知功能障碍:评估神经炎症的多模态功能成像研究。
背景:前列腺癌症的雄激素剥夺治疗(ADT)可能是认知障碍(CI)的一个原因。痴呆和阿尔茨海默病的CI与神经炎症有关。在本研究中,我们研究了神经炎症在ADT相关CI中的潜在作用。方法:癌症前列腺患者ADT≥3 根据访谈时的自我报告,月被归类为ADT突发CI或正常认知(NC)。使用正电子发射断层扫描(PET)和转运蛋白(TSPO)放射性配体[11C]-PBR28评估神经炎症。[11C]-PBR28在不同大脑区域的摄取被量化为标准摄取值(SUVR,标准化为小脑),并与血氧水平依赖性功能磁共振成像(BOLD-fMRI)选择反应时间任务(CRT)激活图相关。结果:11例患者接受了PET检查:4例报告CI(rCI),6例报告NC(rNC),1例未记录状态。PET未显示SUVR在区域或全球范围内的任何组间差异。两组对CRT的大脑激活没有差异。无论报告的认知状态如何,PET-TSPO信号与海马、杏仁核和内侧皮层的CRT激活之间都存在很强的相关性。结论:PET-TSPO检测rCI和rNC患者的神经炎症没有差异。然而,我们推测,TSPO摄取与大脑中参与记忆且已知具有高雄激素受体表达介导可塑性的区域(海马体和杏仁核)的BOLD fMRI激活之间的强相关性可能反映了ADT的炎症效应,其具有代偿性上调/增加的突触功能。有必要对这种成像读数进行进一步研究,以研究ADT相关的CI。
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来源期刊
Prostate Cancer
Prostate Cancer ONCOLOGY-
CiteScore
2.70
自引率
0.00%
发文量
9
审稿时长
13 weeks
期刊介绍: Prostate Cancer is a peer-reviewed, Open Access journal that provides a multidisciplinary platform for scientists, surgeons, oncologists and clinicians working on prostate cancer. The journal publishes original research articles, review articles, and clinical studies related to the diagnosis, surgery, radiotherapy, drug discovery and medical management of the disease.
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