Cognitive impairment and associations with structural brain networks, endocrine status, and risk genotypes in patients with newly diagnosed prostate cancer referred to androgen-deprivation therapy

Background: Evidence suggests that patients with prostate cancer (PCPs) receiving androgen-deprivation therapy (ADT) are at risk for cognitive impairment). Research with other populations with cancer indicates that cognitive impairment may also occur before systemic treatment. The authors assessed cognitive impairment in untreated PCPs referred to ADT and explored associations with structural brain networks, endocrine status, and selected genotypes.

Methods: Forty untreated PCPs and 27 healthy controls (HCs) who completed a questionnaire package underwent neuropsychological testing, magnetic resonance imaging, and blood sampling. Cognitive impairment was defined as a z score ≤-2 on 1 neuropsychological test or ≤-1.5 on 2 neuropsychological tests. Structural brain networks were investigated using diffusion-weighted imaging and graph theory. Associations of cognitive performance with patient-reported outcome measures (PROMs), brain networks, testosterone levels, and genotypes (apolipoprotein ε [APOE], catechol-O-methyltransferase [COMT], and brain-derived neurotrophic factor [BDNF]) were explored.

Results: PCPs performed poorer than HCs on 7 of 15 neuropsychological tests and exhibited a higher frequency of cognitive impairment (57.5% vs 22.2%; P ≤ .01 to .03). All neuropsychological outcomes were associated with ≥1 PROM (P ≤ .01 to .04). Compared with the HC group, the PCP group exhibited altered global network organization as well as disrupted regional network characteristics in frontal and temporal regions (P < .01). PCPs had lower testosterone levels (P < .01) than HCs, which correlated with better visuospatial performance (r = -0.33; P = .04). No effects were found of APOE, COMT, or BDNF.

Conclusions: The current results suggest that untreated PCPs may demonstrate cognitive impairment and that psychological and behavioral symptoms (PROMs), as well as impairment in structural brain networks, might be the underlying mechanisms.