The Risk of New Onset Dementia and/or Alzheimer Disease among Patients with Prostate Cancer Treated with Androgen Deprivation Therapy: A Systematic Review and Meta-Analysis

Abstract

Purpose: Androgen deprivation therapy is a standard therapy for some patients with localized and almost all patients with metastatic prostate cancer. Although several clinical cohort studies have identified an impact of androgen deprivation therapy on cognitive function, the previous reviews were not able to perform a well designed quantitative synthesis to summarize the risk of dementia and/or Alzheimer disease. Consequently there is still a lack of systematic review and meta-analysis regarding the impact of this risk including more recent studies. Materials and Methods: We conducted a systematic review and meta-analysis of the literature assessing the differential incidence of dementia and/or Alzheimer disease as outcomes in patients with prostate cancer who did vs did not receive androgen deprivation therapy. We queried PubMedÒ and Web of ScienceÔ databases from January 1 to 3, 2020. We used random or fixed effects meta-analytic models in the presence or absence of heterogeneity per the I 2 statistic. We performed 6 meta-analyses for all cause dementia, Alzheimer disease and all cause dementia or Alzheimer disease according to the duration of androgen deprivation therapy (up to 12 or more than 12 months). Results: A total of 14 studies were selected after considering inclusion and exclusion criteria. Nine of them reported all cause dementia (ie all types of dementia including Alzheimer disease), with 8 reporting Alzheimer disease. Five studies assessed these outcomes according to the duration of androgen deprivation therapy. The risk of new onset dementia (all cause) and Alzheimer disease was higher in patients with prostate cancer who received androgen deprivation therapy compared to those who did not (HR 1.21, 95% CI 1.11e1.33 and HR 1.16, 95% CI 1.09e1.24). The risk of dementia (all cause) was higher in patients with prostate cancer who received androgen deprivation therapy for more than 12 months (HR 1.36, 95% CI 1.07e1.72); however, for those who had less than 12 months of androgen deprivation therapy exposure the difference was not statistically significant 1.06 (95% CI 0.77e1.28). There was no association between the androgen deprivation therapy duration and the risk of Alzheimer disease (HR 1.21, 95% CI 0.97e1.51 for exposure up to 12 months and HR 1.39, 95% CI 0.69e2.79 for exposure greater than 12 months).

Association between SARS-CoV-2 infection and disease severity among prostate cancer patients on androgen deprivation therapy: a systematic review and meta-analysis

“…ADT, the mainstay treatment in advanced and metastatic PCa patients, is associated with several adverse events (AEs) such as cardiac diseases and metabolic syndrome, osteoporosis, fractures, and cognitive disorders. This, indeed, can affect PCa patients' performance status and overall survival [23][24][25]. O'Callaghan et al calculated that to prevent one COVID-19 case, 434 men need to be treated with ADT [26].…”

The Efficacy and Safety of Relugolix Compared with Degarelix in Advanced Prostate Cancer Patients: A Network Meta-analysis of Randomized Trials

“…Consequently, a longer follow-up comparison was not feasible in the current network meta-analysis. Cardiac diseases, metabolic syndrome, and cognitive disorders are the main AEs of long-term ADT [7,22]. Thus, we have to be cautious about the results of the present study and wait for the longer follow-up results of the HERO trial.…”

Biomarkers to Evaluate Androgen Deprivation Therapy for Prostate Cancer and Risk of Alzheimer’s Disease and Neurodegeneration: Old Drugs, New Concerns

“…The more recent meta-analysis from Sari Motlagh et al. that does not suffer these limitations, established a stronger link between ADT use and the development of AD/dementia ( 15 ).…”

“…In an attempt to perform a well-designed quantitative synthesis to summarize the risk of dementia and/or AD disease with ADT use, a systematic review and meta-analysis of the literature was conducted very recently by Sari Motlagh et al. ( 15 ). ADT consisted of GnRH agonists or antagonist (use of anti-androgens only or orchiectomy were excluded) and the control group included only PCa patients.…”

“…We will focus on the most recent and largest cohort studies results on the subject (Table 1). We will begin by the studies establishing a correlation between cognitive impairment/AD and ADT (9,10,(12)(13)(14), then describe two studies which question this potential link (8,11) and finally, we will present a recent meta-analysis of these observational cohort studies conducted by Sari Motlagh et al (15).…”