Androgen deprivation therapy and cognitive decline-associations with brain connectomes, endocrine status, and risk genotypes.
Androgen Antagonists
/ adverse effects
Androgens
Apolipoproteins E
/ genetics
Brain
/ diagnostic imaging
Brain-Derived Neurotrophic Factor
/ genetics
Catechol O-Methyltransferase
/ genetics
Cognitive Dysfunction
/ chemically induced
Connectome
Genotype
Humans
Male
Prostatic Neoplasms
/ drug therapy
Testosterone
Journal
Prostate cancer and prostatic diseases
ISSN: 1476-5608
Titre abrégé: Prostate Cancer Prostatic Dis
Pays: England
ID NLM: 9815755
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
27
01
2021
accepted:
19
05
2021
revised:
30
04
2021
pubmed:
6
6
2021
medline:
14
6
2022
entrez:
5
6
2021
Statut:
ppublish
Résumé
Evidence suggests that prostate cancer (PC) patients undergoing androgen deprivation therapy (ADT) are at risk for cognitive decline (CD), but the underlying mechanisms are less clear. In the present study, changes in cognitive performance and structural brain connectomes in PC patients undergoing ADT were assessed, and associations of cognitive changes with endocrine status and risk genotypes were explored. Thirty-seven PC patients underwent cognitive assessment, structural MRI, and provided blood samples prior to ADT and after 6 months of treatment. Twenty-seven age- and education-matched healthy controls (HCs) underwent the same assessments. CD was determined using a standardized regression-based approach and defined as z-scores ≤ -1.64. Changes in brain connectomes were evaluated using graph theory. Associations of CD with testosterone levels and genotypes (APOE, COMT, BDNF) were explored. Compared with HCs, PC patients demonstrated reduced testosterone levels (p < 0.01) and higher rates of decline for 13 out of 15 cognitive outcomes, with three outcomes related to two cognitive domains, i.e., verbal memory and visuospatial learning and memory, reaching statistical significance (p ≤ 0.01-0.04). Testosterone level changes did not predict CD. COMT Met homozygote PC patients evidenced larger reductions in visuospatial memory compared with Val carriers (p = 0.02). No between-group differences were observed in brain connectomes across time, and no effects were found of APOE and BDNF. Our results indicate that PC patients undergoing ADT may evidence CD, and that COMT Met homozygotes may be at increased risk of CD. The results did not reveal changes in brain connectomes or testosterone levels as underlying mechanisms. More research evaluating the role of ADT-related disruption of the dynamics of the hypothalamic-pituitary-gonadal axis is needed.
Sections du résumé
BACKGROUND
Evidence suggests that prostate cancer (PC) patients undergoing androgen deprivation therapy (ADT) are at risk for cognitive decline (CD), but the underlying mechanisms are less clear. In the present study, changes in cognitive performance and structural brain connectomes in PC patients undergoing ADT were assessed, and associations of cognitive changes with endocrine status and risk genotypes were explored.
METHODS
Thirty-seven PC patients underwent cognitive assessment, structural MRI, and provided blood samples prior to ADT and after 6 months of treatment. Twenty-seven age- and education-matched healthy controls (HCs) underwent the same assessments. CD was determined using a standardized regression-based approach and defined as z-scores ≤ -1.64. Changes in brain connectomes were evaluated using graph theory. Associations of CD with testosterone levels and genotypes (APOE, COMT, BDNF) were explored.
RESULTS
Compared with HCs, PC patients demonstrated reduced testosterone levels (p < 0.01) and higher rates of decline for 13 out of 15 cognitive outcomes, with three outcomes related to two cognitive domains, i.e., verbal memory and visuospatial learning and memory, reaching statistical significance (p ≤ 0.01-0.04). Testosterone level changes did not predict CD. COMT Met homozygote PC patients evidenced larger reductions in visuospatial memory compared with Val carriers (p = 0.02). No between-group differences were observed in brain connectomes across time, and no effects were found of APOE and BDNF.
CONCLUSIONS
Our results indicate that PC patients undergoing ADT may evidence CD, and that COMT Met homozygotes may be at increased risk of CD. The results did not reveal changes in brain connectomes or testosterone levels as underlying mechanisms. More research evaluating the role of ADT-related disruption of the dynamics of the hypothalamic-pituitary-gonadal axis is needed.
Identifiants
pubmed: 34088994
doi: 10.1038/s41391-021-00398-1
pii: 10.1038/s41391-021-00398-1
doi:
Substances chimiques
Androgen Antagonists
0
Androgens
0
Apolipoproteins E
0
Brain-Derived Neurotrophic Factor
0
Testosterone
3XMK78S47O
COMT protein, human
EC 2.1.1.6
Catechol O-Methyltransferase
EC 2.1.1.6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
208-218Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature Limited.
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