Androgen deprivation therapy and cognitive decline—associations with brain connectomes, endocrine status, and risk genotypes

Buskbjerg, Cecilie R; Amidi, Ali; Buus, Simon; Gravholt, Claus Højbjerg; Hosseini, S. M. Hadi; Zachariae, Robert

doi:10.1038/s41391-021-00398-1

Cited by 13 publications

(11 citation statements)

References 55 publications

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“…47 After 6 months, patients who were receiving leuprolide and bicalutamide had a higher rate of performance decline than the HC group on verbal memory and visual memory. 56 This finding was also observed after 9 months with intermittent leuprolide acetate in association with flutamide or bicalutamide. 30 After 12 months, a randomized controlled trial showed that performance on a verbal memory test was lower in the ADT group than in the PC− group.…”

Section: Studies With Control Groupmentioning

confidence: 67%

Does hormone therapy impact cognition in patients with prostate cancer? A systematic review and meta‐analysis

Boué,

Joly,

Lequesne

et al. 2024

Cancer

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BackgroundHormone therapy, which is widely prescribed for prostate cancer, might induce cognitive impairment and affect the autonomy of elderly patients. However, previous studies provided conflicting results. The aim of this systematic review and meta‐analysis was to synthesize the longitudinal impact of hormone therapy on objective (cognitive tests) and subjective (questionnaires) cognition.MethodsA search was performed of the PubMed, Web of Science, and PsycINFO databases. Studies that longitudinally assessed cognition in patients undergoing androgen‐deprivation therapy and new‐generation hormone therapy were considered. To perform a meta‐analysis, available scores were aggregated and classified into six objective domains and one subjective domain. Weighted mean effect sizes were computed using a random effect model.ResultsTwenty studies were included in the systematic review (1440 patients), and 15 could be included in the meta‐analysis (1093 patients). In the systematic review, 20%–50% of patients had objective cognitive impairment before treatment initiation. The meta‐analysis revealed a decline in subjective cognition (g = −0.44; p = .03) with androgen‐deprivation therapy and new‐generation hormone therapy. All other effect sizes were small (from g = −0.02 to g = 0.18), and none of them indicated a significant decline in objective cognition. Significant heterogeneity was observed in all domains of objective cognition.ConclusionsThis synthesis presents the first meta‐analytic evidence of the negative impact of androgen‐deprivation therapy and new‐generation hormone therapy on subjective cognition. In contrast, there was no conclusive evidence of a decline in objective cognition. The high heterogeneity underscores the need for homogeneous cognitive research on prostate cancer.Plain Language Summary There is no consensus on the cognitive impairment induced by hormone therapy for prostate cancer, despite the implications for patients’ care and daily life. This synthesis of published studies demonstrated an increase in perceived cognitive difficulties but did not prove a decline in cognitive performance during treatment.

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Section: Studies With Control Groupmentioning

confidence: 67%

Does hormone therapy impact cognition in patients with prostate cancer? A systematic review and meta‐analysis

Boué,

Joly,

Lequesne

et al. 2024

Cancer

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“…Impaired cognitive function associated with cancer is often referred to as cancer-related cognitive impairment (CRCI); however, this is a broad diagnosis across many diseases. This manuscript focuses on CI as it relates to PCa and PCa treatment as there is little actionable clinical data in this healthcare space [ 5 , 12 ]. For simplicity, and to help bring awareness to the gap in this clinical niche, CI associated with PCa treatment is referred to as prostate cancer treatment-related cognitive impairment (PCa-TRCI) in this manuscript.…”

Section: Introductionmentioning

confidence: 99%

Treatment-Related Cognitive Impairment in Patients with Prostate Cancer: Patients’ Real-World Insights for Optimizing Outcomes

Cowan,

Olivier,

Tombal

et al. 2023

Adv Ther

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Cognitive impairment (CI) is an issue that needs to be at the forefront of unmet healthcare needs in patients with prostate cancer (PCa) as it can negatively impact quality of life during long-term care. CI in patients with prostate cancer is thought to be influenced by treatment, androgen deprivation therapy (ADT), and novel androgen receptor (AR) pathway inhibitors in particular; however, current understanding is limited on how treatment affects cognition. Additionally, the experience of patients with CI who are receiving PCa treatment is not well understood or represented in clinical literature, which is a barrier to optimal patient outcomes in managing prostate cancer treatment-related cognitive impairment (PCa-TRCI). To help understand the patient journey and elucidate management gaps in PCa-TRCI, an international roundtable of healthcare provider and patient panelists was convened. The panelists focused on four key topic areas: (1) the patient experience when afflicted with, or at risk of, PCa-TRCI, (2) the physical, emotional, and social impact of CI on patients’ quality of life (QoL), (3) the challenges that patients with PCa-TRCI face, and their impact on clinical decision-making, and (4) ways in which managing PCa-TRCI should evolve to improve patient outcomes. The purpose of the roundtable was to include patients in a direct discussion with healthcare providers (HCPs) regarding the patient journey and highlight real-world evidence of areas where patient outcomes could be improved in the absence of clinical evidence. The resulting discussion highlighted important healthcare gaps for patients with, and at risk of, PCa-TRCI and offered potential solutions as a roadmap to effective medicine. Graphical Abstract

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“…Genetic mutations associated with Alzheimer's disease have been identified in patients with prostate cancer [34,35], and variants of several genes, including the apolipoprotein E gene and the rs1047776 single-nucleotide polymorphism in GNB3, may increase the risk of cognitive dysfunction [6,10,36 between apolipoprotein E, brain-derived neurotrophic factor genotype, and treatment-related cognitive decline was observed. Patients with prostate cancer treated with ADT did not demonstrate alterations in brain connectome metrics over time compared to healthy controls [37]. Crawford et al also review the case for a potential correlation between higher serum levels of follicle-stimulating hormone, ADT, and poorer cognitive performance, suggesting a biological rationale for cognitive change in patients with prostate cancer receiving ADT [38].…”

Section: Drug Treatment and Other Factors Associated With Cognitive D...mentioning

confidence: 99%

Assessment and Management of Cognitive Function in Patients with Prostate Cancer Treated with Second-Generation Androgen Receptor Pathway Inhibitors

et al. 2022

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Preservation of cognitive function is an important outcome in oncology. Optimal patient management requires an understanding of cognitive effects of the disease and its treatment and an efficacious approach to assessment and management of cognitive dysfunction, including selection of treatments to minimize the risk of cognitive impairment. Awareness is increasing of the potentially detrimental effects of cancer-related cognitive dysfunction on functional independence and quality of life. Prostate cancer occurs most often in older men, who are more likely to develop cognitive dysfunction than younger individuals; this population may be particularly vulnerable to treatment-related cognitive disorders. Prompt identification of treatment-induced cognitive dysfunction is a crucial aspect of effective cancer management. We review the potential etiologies of cognitive decline in patients with prostate cancer, including the potential role of androgen receptor pathway inhibitors; commonly used tools for assessing cognitive function validated in metastatic castration-resistant prostate cancer and adopted in non-metastatic castration-resistant prostate cancer trials; and strategies for management of cognitive symptoms. Many methods are currently used to assess cognitive function. The prevalence and severity of cognitive dysfunction vary according to the instruments and criteria applied. Consensus on the definition of cognitive dysfunction and on the most appropriate approaches to quantify its extent and progression in patients treated for prostate cancer is lacking. Evidence-based guidance on the appropriate tools and time to assess cognitive function in patients with prostate cancer is required. Plain Language SummaryMen with prostate cancer are usually elderly and may have other health conditions. Old age, poor health, and some medications can all affect a person's ability to think clearly, make sound judgments, remember things, and learn new information. These mental difficulties can make it hard for people to do day-to-day tasks such as shopping or making a meal, looking after themselves, or taking medications correctly. People may also have problems with friendships and relationships. Therefore, before a man starts treatment for prostate cancer, he and his doctor must consider the likelihood that his mental ability might be affected by the treatment in order to choose the most suitable treatment option. Initially, the doctor can use short screening tests, such as asking the patient to remember and repeat numbers or words, draw objects, name things in a picture, or complete a survey. If these tests show that the patient might be having mental difficulties, he may be invited for additional tests with a specialist, called a neuropsychologist. A patient with, or at risk of, mental difficulties will be offered a care plan, which might include one or more of the following: selecting or switching treatments to avoid side effects; using memory aids; treatment for pain, difficulty sleeping, depression, or other problems that mi...

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Androgen deprivation therapy and cognitive decline—associations with brain connectomes, endocrine status, and risk genotypes

Cited by 13 publications

References 55 publications

Does hormone therapy impact cognition in patients with prostate cancer? A systematic review and meta‐analysis

Does hormone therapy impact cognition in patients with prostate cancer? A systematic review and meta‐analysis

Treatment-Related Cognitive Impairment in Patients with Prostate Cancer: Patients’ Real-World Insights for Optimizing Outcomes

Assessment and Management of Cognitive Function in Patients with Prostate Cancer Treated with Second-Generation Androgen Receptor Pathway Inhibitors

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