Effects of androgen deprivation on brain function in prostate cancer patients – a prospective observational cohort analysis

Abstract

BackgroundDespite a lack of consensus regarding effectiveness, androgen deprivation therapy (ADT) is a common treatment for non-metastatic, low-risk prostate cancer. To examine a particular clinical concern regarding the possible impact of ADT on cognition, the current study combined neuropsychological testing with functional magnetic resonance imaging (fMRI) to assess both brain activation during cognitive performance as well as the integrity of brain connectivity.MethodsIn a prospective observational cohort analysis of men with non-metastatic prostate cancer at a Veterans Affairs medical center, patients receiving ADT were compared with patients not receiving ADT at baseline and at 6 months. Assessments included fMRI, the N-back task (for working memory), the stop-signal task (for cognitive control), and a quality of life questionnaire.ResultsAmong 36 patients enrolled (18 in each group), 30 completed study evaluations (15 in each group); 5 withdrew participation and 1 died. Results for the N-back task, stop-signal task, and quality of life were similar at 6 months vs. baseline in each group. In contrast, statistically significant associations were found between ADT use (vs. non use) and decreased medial prefrontal cortical activation during cognitive control, as well as decreased connectivity between the medial prefrontal cortex and other regions involved with cognitive control.ConclusionsAlthough ADT for 6 months did not affect selected tests of cognitive function, brain activations during cognitive control and functional brain connectivity were impaired on fMRI. The long-term clinical implications of these changes are not known and warrant future study.

Changes in cerebral metabolic activity in men undergoing androgen deprivation therapy for non-metastatic prostate cancer

“…Chao and colleagues (2012) reported decreased medial prefrontal cortical activation during a working memory task, as well as decreased connectivity between the medial prefrontal cortex and other regions in men on ADT compared to controls. 52 …”

Brain network alterations and vulnerability to simulated neurodegeneration in breast cancer

“…Although most cancer diagnoses originate outside the central nervous system (CNS), cognitive decline affects an estimated 19-78% of these patients (Wefel and Schagen, 2012). Neuroimaging studies suggest that this cognitive impairment stems from subtle but diffuse brain injury (Chao, et al, 2012; D'Agata, et al, 2013; Hsieh, et al, 2014; Koppelmans, et al, 2014) [see reviews by: (de Ruiter and Schagen, 2013; McDonald and Saykin, 2013; Scherling and Smith, 2013)].…”

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

“…Furthermore, these changes were positively correlated with changes in executive function in the aerobic training group, but the stretching/balance group also showed alterations in functional connectivity, possibly representing experience-dependent plasticity (Voss et al 2010). These findings may be relevant to men with PCa treated with ADT as there is some evidence from a study of 30 PCa survivors (median age 68 years), which found that 6 months of ADT was associated with decreased grey matter volume, reduced brain functional connectivity and reduced neural activations during cognitive control tasks (Chao et al 2012(Chao et al , 2013. Collectively, the current evidence indicate that regular exercise training can offer protective benefits to cognitive function in healthy older adults, but in men with PCa receiving ADT, the direct link between exercise and cognitive function has not been established.…”

“…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). Thirteen prospective studies have objectively assessed cognitive function in patients receiving ADT (Table 1) (Green et al 2002, Cherrier et al 2003, 2009, Salminen et al 2003, Almeida et al 2004, Alibhai et al 2010, Matousek & Sherwin 2010, Mohile et al 2010, Chao et al 2012, Tan et al 2013, Gonzalez et al 2015. Five of these studies reported no effect (Almeida et al 2004, Matousek & Sherwin 2010, Mohile et al 2010, Chao et al 2012, Tan et al 2013, which is likely related in part to methodological differences in participant characteristics, study design and analyses.…”

“…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.…”