Cognitive functioning in men receiving androgen deprivation therapy for prostate cancer: a systematic review and meta-analysis

Abstract

Purpose Prior research examining the impact of androgen deprivation therapy (ADT) for prostate cancer on cognitive performance has found inconsistent relationships. The purpose of this study was to systematically review the existing literature and determine the effect of ADT on performance across seven cognitive domains using meta-analysis. Methods A search of PubMed Medline, PsycINFO, Cochrane Library, and Web of Knowledge/Science databases yielded 157 unique abstracts reviewed by independent pairs of raters. Fourteen studies with a total of 417 patients treated with ADT were included in the meta-analysis. Objective neuropsychological tests were categorized into seven cognitive domains: attention/working memory, executive functioning, language, verbal memory, visual memory, visuomotor ability, and visuospatial ability. Results Separate effect sizes were calculated for each cognitive domain using pairwise comparisons of patients who received ADT with 1) prostate cancer patient controls, 2) non-cancer controls, or 3) ADT patients’ own pre-ADT baselines. Patients treated with ADT performed worse than controls or their own baseline on visuomotor tasks (g=−0.67, p=.008; n=193). The magnitude of the deficits was larger in studies with a shorter time to follow-up (p=.04). No significant effect sizes were observed for the other six cognitive domains (p=.08=–.98). Conclusions Prostate cancer patients who received ADT performed significantly worse on visuomotor tasks compared to non-cancer control groups. These findings are consistent with the known effects of testosterone on cognitive functioning in healthy men. Knowledge of the cognitive effects of ADT may help patients and providers better understand the impact of ADT on quality of life.

Cognitive decline in prostate cancer patients undergoing ADT: a potential role for exercise training

“…However, in men with PCa treated with ADT, the rate of decline in these processes appears to be accelerated (McGinty et al 2014). Furthermore, the use of ADT has been associated with an almost two-fold increased risk for developing Alzheimer's disease (AD), with the risk increasing with treatment duration (Nead et al 2016).…”

“…Brain imaging studies have also shown that the adverse effects to spatial ability and memory are related to changes in cerebral function and brain volume (Cherrier et al 2009, Chao et al 2012. However, a meta-analysis of 14 studies that objectively measured cognitive function in PCa survivors on ADT confirmed that the largest effect size in relation to ADT and cognitive function was for the visuomotor control domain (effect size, g = −0.67) (McGinty et al 2014), which may indicate an effect of reduced testosterone on tasks involving both vision and manual manipulation.…”

“…In summary, the available evidence indicates that ADT adversely affects the cognitive domains of verbal, visual, spatial and working memory (Green et al 2002, Beer et al 2006, Cherrier et al 2009), spatial reasoning and spatial ability (Cherrier et al 2003(Cherrier et al , 2009, psychomotor and visuomotor function (Green et al 2004, Salminen et al 2004, auditory learning (Bussiere et al 2005), executive function and processing speed (Green et al 2002, Cherrier et al 2009, with the most significant effects on visuomotor ability (McGinty et al 2014). Given that a randomised study design of ADT use is not ethical for men with advanced PCa, future observational studies that aim to measure cognitive function in PCa patients should closely adhere to current guidelines for assessing the cognitive function in cancer patients, such as those recommended by the International Cognition and Cancer Task Force (ICCTF) (Wefel et al 2011).…”

“…Combined or multimodal exercise interventions that include a motor component (movement speed, balance, motor coordination and flexibility) have also been shown to improve cognitive function in older adults (VoelckerRehage et al 2010). Although questions still remain as to the optimal type and dose of exercise that is most effective to improve cognitive function in older adults, a meta-analysis of single or bimodal exercise trials indicated a small-to-moderate effect on cognitive performance with combined aerobic and PRT compared to aerobic training alone in older adults (Colcombe & Kramer 2003 Kulkarni & Moningi (2015) and McGinty et al (2014). D-KEFS, Delis-Kaplan executive function system; WAIS-R, Wechsler adult intelligence scale-revised; WAIS-III, Wechsler adult intelligence scale-third edition; WMS-R, Wechsler memory scales-re-vised edition; WMS-III, Wechsler memory scales-third edition.…”

“…Despite improving survival, research has consistently reported a range of adverse effects associated with the use of ADT including deterioration in 24:4 musculoskeletal health, an increase in cardiometabolic risk and a reduction in health-related quality of life (HR-QoL) (Gardner et al 2014). A growing body of evidence indicates that ADT may also adversely affect cognitive function, including information processing (Green et al 2002), spatial abilities (Cherrier et al 2009) and memory (Bussiere et al 2005), visuo-motor speed (McGinty et al 2014) and executive function (Cherrier et al 2009). However, current guidelines for the assessment and management of PCa for men treated with ADT do not recommend an assessment of cognitive function or methods for attenuating cognitive decline associated with treatment (Bussiere et al 2005, Grossmann & Zajac 2011.…”