Sleep disturbance and neurocognitive outcomes in older patients with breast cancer: Interaction with genotype Journal Article


Authors: Carroll, J. E.; Small, B. J.; Tometich, D. B.; Zhai, W.; Zhou, X.; Luta, G.; Ahles, T. A.; Saykin, A. J.; Nudelman, K. N. H.; Clapp, J. D.; Jim, H. S.; Jacobsen, P. B.; Hurria, A.; Graham, D.; McDonald, B. C.; Denduluri, N.; Extermann, M.; Isaacs, C.; Dilawari, A. A.; Root, J.; Stern, R. A.; Mandelblatt, J. S.; for the Thinking and Living With Cancer Study
Article Title: Sleep disturbance and neurocognitive outcomes in older patients with breast cancer: Interaction with genotype
Abstract: Background: Sleep disturbance and genetic profile are risks for cognitive decline in noncancer populations, yet their role in cancer-related cognitive problems remains understudied. This study examined whether sleep disturbance was associated with worse neurocognitive outcomes in breast cancer survivors and whether sleep effects on cognition varied by genotype. Methods: Newly diagnosed female patients (n = 319) who were 60 years old or older and had stage 0 to III breast cancer were recruited from August 2010 to December 2015. Assessments were performed before systemic therapy and 12 and 24 months later. Neuropsychological testing measured attention, processing speed, executive function, learning, and memory; self-perceived cognitive functioning was also assessed. Sleep disturbance was defined by self-report of routine poor or restless sleep. Genotyping included APOE, BDNF, and COMT polymorphisms. Random effects fluctuation models tested associations of between-person and within-person differences in sleep, genotype, and sleep-genotype interactions and cognition and controlled for age, reading level, race, site, and treatment. Results: One-third of the patients reported sleep disturbances at each time point. There was a sleep-APOE ε4 interaction (P =.001) in which patients with the APOE ε4 allele and sleep disturbances had significantly lower learning and memory scores than those who were APOE ε4-negative and without sleep disturbances. There was also a sleep disturbance–COMT genotype interaction (P =.02) in which COMT Val carriers with sleep disturbances had lower perceived cognition than noncarriers. Conclusions: Sleep disturbance was common and was associated with worse cognitive performance in older breast cancer survivors, especially those with a genetic risk for cognitive decline. Survivorship care should include sleep assessments and interventions to address sleep problems. © 2019 American Cancer Society
Keywords: adult; controlled study; major clinical study; cancer staging; disease association; breast cancer; genetic association; genotype; self report; gene interaction; brain derived neurotrophic factor; scoring system; neuropsychological test; cognition; genetic risk; memory; attention; sleep disorder; dna polymorphism; learning; bdnf; older; sleep; apolipoprotein e; pittsburgh sleep quality index; executive function; catechol methyltransferase; human; female; priority journal; article; apoe; comt; apoe gene; bdnf gene; comt gene; processing speed; self perceived cognitive functioning
Journal Title: Cancer
Volume: 125
Issue: 24
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 2019-12-15
Start Page: 4516
End Page: 4524
Language: English
DOI: 10.1002/cncr.32489
PUBMED: 31553501
PROVIDER: scopus
PMCID: PMC6891125
DOI/URL:
Notes: Source: Scopus
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MSK Authors
  1. Tim A Ahles
    104 Ahles
  2. James Charles Root
    50 Root