Risk of Dementia and Depression in Young and Middle-aged Men Presenting with Nonmetastatic Prostate Cancer Treated with Androgen Deprivation Therapy

Tully, Karl; Nguyen, David‐Dan; Herzog, Peter; Jin, Ginger Zhe; Noldus, Joachim; Nguyen, Paul L.; Kibel, Adam S.; Sun, Maxine; McGregor, Bradley A.; Basaria, Shehzad; Trinh, Quoc‐Dien

doi:10.1016/j.euo.2019.08.003

Cited by 26 publications

(19 citation statements)

References 34 publications

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“… 23 One of the most recent large retrospective cohort studies using TRICARE Military Database investigated the effect of ADT, particularly on the risk of depression along with those of dementia in 9,117 men (40–64 years old) diagnosed with localized PCa. 20 In this study, patients with ADT were determined to have a significantly higher risk of depression (HR, 2.07) and dementia (HR, 1.70). A dose–response relationship was noted between outcome and ADT duration.…”

Section: Dementia and Adt In Men With Prostate Cancermentioning

confidence: 98%

“… 12 , 13 More recently, reports on the association of ADT with increased risk of Alzheimer's disease (AD) and other types of dementia based on large electronic databases have also demonstrated contradictory results. 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 Apart from these controversies, the prevalence of dementia in South Korea among elderly men (≥65 years) was recorded to be as high as 9.2%, 24 which indicates that exploring the correlation between ADT and risk of dementia is based on a population already at increased risk and therefore requires careful considerations. In this current review, we discuss the general impact of androgen level on cognitive function and further examine the results from previous studies that have investigated the association of ADT with cognitive dysfunction or risk of dementia in PCa patients.…”

Section: Introductionmentioning

confidence: 99%

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Androgen deprivation therapy and risk of cognitive dysfunction in men with prostate cancer: is there a possible link?

Shim

Bang

et al. 2022

Prostate International

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Section: Dementia and Adt In Men With Prostate Cancermentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Androgen deprivation therapy and risk of cognitive dysfunction in men with prostate cancer: is there a possible link?

Shim

Bang

et al. 2022

Prostate International

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“…Tully et al [ 31 ] used the TRICARE military database to show evidence of a significant correlation between ADT and dementia (HR=1.7) and depression (HR=2.07) in 9,117 40- to 64-year-old patients with localized PC either receiving ADT or not. The authors calculated an overall increased risk of 70% for the patients aged 40–64 years with ADT and 107% of depression compared to the non-ADT group, similar to earlier findings [ 20 32 ].…”

Section: Main Bodymentioning

confidence: 99%

How Does Androgen Deprivation Therapy Affect Mental Health including Cognitive Dysfunction in Patients with Prostate Cancer?

Lee

Park

Joung

et al. 2021

World J Mens Health

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Androgen deprivation therapy (ADT) is used to block the release of androgen in prostate cancer to promote the regression of cancer cells, and hence, disease progression. Its indication has been widened from the metastatic setting to the localized setting in prostate cancer. Long-term ADT for suppressing androgen release leads to a rapid decrease in androgen, termed as andropause, resulting in several dose and duration dependent adverse effects, including cognitive dysfunction such as dementia. Many retrospective and prospective studies, as well as meta-analyses, have attempted to confirm the crucial relationship between ADT and cognitive dysfunction, but pro and contrary opinions regarding this issue are ongoing owing to the absence of randomized controlled trials. Additionally, several recent studies have suggested the negative effects of dose-and duration-dependent ADT on cognitive dysfunction, especially in 40-65-year-old patients with prostate cancer, who are currently active workers in the society. This review article discusses several studies examining the influence of ADT on mental health based on diverse significant perspectives, especially cognitive dysfunction.

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“…There are well-documented neurocognitive side effects due to androgen ablation that have raised concerns regarding a potential association between androgen deprivation and neurodegenerative disease. [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] Reduced plasma level of testosterone has been reported in Alzheimer's, Multiple sclerosis, Parkinson's, and ALS (reviewed in Bianchi et al, 2020). 36 In Alzheimer's disease, reduced circulating and brain testosterone was reported and correlated with AD pathology suggesting that low testosterone is a factor that contributes to, rather than results from, the development of AD (reviewed in Rosario et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…There are well‐documented neurocognitive side effects due to androgen ablation that have raised concerns regarding a potential association between androgen deprivation and neurodegenerative disease 19–35 . Reduced plasma level of testosterone has been reported in Alzheimer's, Multiple sclerosis, Parkinson's, and ALS (reviewed in Bianchi et al, 2020) 36 .…”

Section: Introductionmentioning

confidence: 99%

Androgen‐targeting therapeutics mitigate the adverse effect of GnRH agonist on the risk of neurodegenerative disease in men treated for prostate cancer

et al. 2022

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Background Prostate cancer and multiple neurodegenerative diseases (NDD) share an age‐associated pattern of onset. Therapy of prostate cancer is known to impact cognitive function. The objective of this study was to determine the impact of multiple classes of androgen‐targeting therapeutics (ATT) on the risk of NDD. Methods A retrospective cohort study of men aged 45 and older with prostate within the US‐based Mariner claims data set between January 1 and 27, 2021. A propensity score approach was used to minimize measured and unmeasured selection bias. Disease risk was determined using Kaplan–Meier survival analyses. Results Of the 1,798,648 men with prostate cancer, 209,722 met inclusion criteria. Mean (SD) follow‐up was 6.4 (1.8) years. In the propensity score‐matched population, exposure to ATT was associated with a minimal increase in NDD incidence (relative risk [RR], 1.07; 95% CI, 1.05–1.10; p < 0.001). However, GnRH agonists alone were associated with significantly increased NDD risk (RR, 1.47; 95% CI, 1.30–1.66; p <0.001). Abiraterone, commonly administered with GnRH agonists and low‐dose prednisone, was associated with a significantly decreased risk (RR, 0.77; 95% CI, 0.68–0.87; p < 0.001) of any NDD. Conclusions Among patients with prostate cancer, GnRH agonist exposure was associated with an increased NDD risk. Abiraterone acetate reduced the risks of Alzheimer's disease and Parkinson's disease conferred by GnRH agonists, whereas the risk for ALS was reduced by androgen receptor inhibitors. Outcomes of these analyses contribute to addressing controversies in the field and indicate that GnRH agonism may be a predictable instigator of risk for NDD with opportunities for risk mitigation in combination with another ATT.

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Risk of Dementia and Depression in Young and Middle-aged Men Presenting with Nonmetastatic Prostate Cancer Treated with Androgen Deprivation Therapy

Cited by 26 publications

References 34 publications

Androgen deprivation therapy and risk of cognitive dysfunction in men with prostate cancer: is there a possible link?

Androgen deprivation therapy and risk of cognitive dysfunction in men with prostate cancer: is there a possible link?

How Does Androgen Deprivation Therapy Affect Mental Health including Cognitive Dysfunction in Patients with Prostate Cancer?

Androgen‐targeting therapeutics mitigate the adverse effect of GnRH agonist on the risk of neurodegenerative disease in men treated for prostate cancer

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