Cognitive Dysfunction in Patients Treated with Androgen Deprivation Therapy: A Multimodality Functional Imaging Study to Evaluate Neuroinflammation
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. Meth...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Hindawi Limited
2023-01-01
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| Series: | Prostate Cancer |
| Online Access: | http://dx.doi.org/10.1155/2023/6641707 |
| _version_ | 1827009852597075968 |
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| author | Azeem Saleem Syed Imran Ali Shah Stephen A. Mangar Christopher Coello Matthew B. Wall Gaia Rizzo Terry Jones Patricia M. Price |
| author_facet | Azeem Saleem Syed Imran Ali Shah Stephen A. Mangar Christopher Coello Matthew B. Wall Gaia Rizzo Terry Jones Patricia M. Price |
| author_sort | Azeem Saleem |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T15:50:37Z |
| format | Article |
| id | doaj.art-1684da15646d4a439f700bff17360ac0 |
| institution | Directory Open Access Journal |
| issn | 2090-312X |
| language | English |
| last_indexed | 2025-02-18T12:55:25Z |
| publishDate | 2023-01-01 |
| publisher | Hindawi Limited |
| record_format | Article |
| series | Prostate Cancer |
| spelling | doaj.art-1684da15646d4a439f700bff17360ac02024-11-02T03:57:26ZengHindawi LimitedProstate Cancer2090-312X2023-01-01202310.1155/2023/6641707Cognitive Dysfunction in Patients Treated with Androgen Deprivation Therapy: A Multimodality Functional Imaging Study to Evaluate NeuroinflammationAzeem Saleem0Syed Imran Ali Shah1Stephen A. Mangar2Christopher Coello3Matthew B. Wall4Gaia Rizzo5Terry Jones6Patricia M. Price7InvicroDepartment of Surgery and CancerImperial UrologyInvicroInvicroInvicroDepartment of RadiologyDepartment of Surgery and CancerBackground. 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.http://dx.doi.org/10.1155/2023/6641707 |
| spellingShingle | Azeem Saleem Syed Imran Ali Shah Stephen A. Mangar Christopher Coello Matthew B. Wall Gaia Rizzo Terry Jones Patricia M. Price Cognitive Dysfunction in Patients Treated with Androgen Deprivation Therapy: A Multimodality Functional Imaging Study to Evaluate Neuroinflammation Prostate Cancer |
| title | Cognitive Dysfunction in Patients Treated with Androgen Deprivation Therapy: A Multimodality Functional Imaging Study to Evaluate Neuroinflammation |
| title_full | Cognitive Dysfunction in Patients Treated with Androgen Deprivation Therapy: A Multimodality Functional Imaging Study to Evaluate Neuroinflammation |
| title_fullStr | Cognitive Dysfunction in Patients Treated with Androgen Deprivation Therapy: A Multimodality Functional Imaging Study to Evaluate Neuroinflammation |
| title_full_unstemmed | Cognitive Dysfunction in Patients Treated with Androgen Deprivation Therapy: A Multimodality Functional Imaging Study to Evaluate Neuroinflammation |
| title_short | Cognitive Dysfunction in Patients Treated with Androgen Deprivation Therapy: A Multimodality Functional Imaging Study to Evaluate Neuroinflammation |
| title_sort | cognitive dysfunction in patients treated with androgen deprivation therapy a multimodality functional imaging study to evaluate neuroinflammation |
| url | http://dx.doi.org/10.1155/2023/6641707 |
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