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.
Aged
Androgen Antagonists
/ therapeutic use
Apolipoproteins E
/ blood
Brain
Brain-Derived Neurotrophic Factor
/ blood
Case-Control Studies
Catechol O-Methyltransferase
/ blood
Cognitive Dysfunction
/ blood
Diffusion Magnetic Resonance Imaging
Genotype
Humans
Male
Neuropsychological Tests
Patient Reported Outcome Measures
Prospective Studies
Prostatic Neoplasms
/ blood
Risk
Testosterone
/ blood
apolipoprotein ε (APOE)
brain-derived neurotrophic factor (BDNF)
catechol-O-methyltransferase (COMT)
cognitive dysfunction
connectome
neuropsychological tests
prostatic neoplasms
testosterone
Journal
Cancer
ISSN: 1097-0142
Titre abrégé: Cancer
Pays: United States
ID NLM: 0374236
Informations de publication
Date de publication:
01 05 2021
01 05 2021
Historique:
revised:
03
11
2020
received:
10
09
2020
accepted:
03
11
2020
pubmed:
23
12
2020
medline:
16
11
2021
entrez:
22
12
2020
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Substances chimiques
Androgen Antagonists
0
Apolipoproteins E
0
Brain-Derived Neurotrophic Factor
0
Testosterone
3XMK78S47O
BDNF protein, human
7171WSG8A2
Catechol O-Methyltransferase
EC 2.1.1.6
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1495-1506Subventions
Organisme : NIMH NIH HHS
ID : R61 MH119289
Pays : United States
Organisme : C. C. Klestrup og hustru Henriette Klestrups Mindelegat
ID : 10761
Organisme : Fabrikant Einar Willumsens Mindelegat
ID : 600073
Organisme : Aase og Ejnar Danielsens Fond
ID : 10-002133
Organisme : Fonden til Laegevidenskabens Fremme
ID : 17-L-0141
Informations de copyright
© 2020 American Cancer Society.
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