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

Abstract

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.

The effects of androgen deprivation on working memory and quality of life in prostate cancer patients: The roles of hypothalamic connectivity

“…Second, working memory represents one aspect of cognitive functions. Studies are needed to employ a more comprehensive battery of neuropsychological tests and other neural metrics to fully investigate potential cognitive dysfunction in prostate cancer patients receiving ADT 65 . Finally, as patients may undergo ADT for a longer duration, the current findings should be considered as specific to patients with only 6 months of exposure to ADT.…”

Cognitive changes and brain connectomes, endocrine status, and risk genotypes in testicular cancer patients–A prospective controlled study

“…In contrast, we have previously reported an association between high CAG repeat length and better verbal memory performance at the baseline assessment of the present TCP sample. 3 This finding, however, was in contrast with previous studies with prostate cancer patients 30 and healthy older men 29 reporting associations between high CAG repeat length and poorer cognitive functions. Accordingly, given the limited and conflicting evidence, it remains unclear how CAG repeat length might exert an effect on cognitive functions in different populations.…”

“…26 Notably, it has also been indicated that CAG repeat length may in itself exert an effect on cognitive functions; however, existing findings have been equivocal. 3,[26][27][28][29][30] Given that only a subgroup of cancer survivors develop CD, it is important to elucidate risk factors, including genetic risk. 1 Previous research has suggested a role for the APOE (e.g., 5,31 ) encoding the glycoprotein apolipoprotein ε, COMT (e.g., 32 ) encoding catechol-O-methyltransferase, and BDNF 1,33 encoding brain-derived neurotrophic factor.…”

A Comprehensive Review and Androgen Deprivation Therapy and Its Impact on Alzheimer’s Disease Risk in Older Men with Prostate Cancer

“…This shows that testosterone levels in the bloodstream may provide neuroprotective effects, as indicated by a direct relationship between testosterone levels and cognitive function. 12 , 65 , 67 , 68 …”