Abstract
Androgen deprivation therapy (ADT) is a standard treatment for prostate cancer patients, routinely used in the palliative or in the curative setting in association with radiotherapy. Among the systemic long-term side effects of ADT, growing data suggest a potentially increased risk of dementia/Alzheimer’s disease in prostate cancer patients treated with hormonal manipulation. While pre-clinical data suggest that androgen ablation may have neurotoxic effects due to Aβ accumulation and increased tau phosphorylation in small animal brains, clinical studies have measured the impact of ADT on long-term cognitive function, with conflicting results, and studies on biological changes after ADT are still lacking. The aim of this review is to report on the current evidence on the association between the ADT use and the risk of cognitive impairment in prostate cancer patients. We will focus on the contribution of Alzheimer’s disease biomarkers, namely through imaging, to investigate potential ADT-induced brain modifications. The evidence from these preliminary studies shows brain changes in gray matter volume, cortical activation and metabolism associated with ADT, however with a large variability in biomarker selection, ADT duration and cognitive outcome. Importantly, no study investigated yet biomarkers of Alzheimer’s disease pathology, namely amyloid and tau. These preliminary data emphasize the need for larger targeted investigations.
Highlights
Prostate cancer (PCa) is the most common cancer diagnosed among men in countries worldwide and it is the second leading cause of men cancer-related death (1)
Aim of the present narrative review is to shed light on clinical and pre-clinical evidence supporting the potential link between androgen ablation and neurocognitive disorders, to explore the current Alzheimer’s disease (AD) biomarkers and to help clinicians integrate this risk for PCa patients care
We will first summarize the clinical results of the main studies assessing the risk of AD/dementia in PCa patients treated with Androgen deprivation therapy (ADT)
Summary
Prostate cancer (PCa) is the most common cancer diagnosed among men in countries worldwide and it is the second leading cause of men cancer-related death (1). We will first summarize the clinical results of the main studies assessing the risk of AD/dementia in PCa patients treated with ADT. Some of these studies (as well as a wellconducted meta-analysis of these studies) establish a correlation between ADT and dementia, but not all of them. These contradictory results can be balanced with the fact that imaging studies in PCa patient’s cohorts show changes in neural activation and brain structure when treated with ADT, and that preclinical data on small animals support an association between testosterone deprivation and AD pathogenesis. We will discuss the clinical repercussions of this specific potential risk for PCa patients as well as the future perspectives in this field
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