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.

Cognitive dysfunction prevalence and associated factors in older breast cancer survivors

“…Other common cancer-related symptoms are also important factors associated with cognitive dysfunction. In this study, anxiety and fatigue were related to subjective cognitive dysfunction; but in contrast to previous studies sleep disturbance was not significantly correlated [17,47]. Although somewhat inconsistent in the literature, other cancer-related symptoms such as anxiety, fatigue, and sleep disturbance have been shown to be significantly correlated with perceived cognitive dysfunction either as independent symptoms or as a cluster of symptoms (identified as the psychoneurological symptom cluster) and these relationships have been noted in all age BCS [43,48] as well as older BCS [13,14,16,47,49].…”

“…Demographic (age and education), medical (comorbidities), and disease factors (time since diagnosis and breast cancer stage) have been shown to be significantly related to cognitive dysfunction [3,[13][14][15]. In addition, other cancer-related symptoms, including depressive symptoms, anxiety, fatigue, and sleep disturbance have been previously linked with cognitive dysfunction [13,14,[16][17][18]. However, in all age BCS and the smaller volume of literature focusing on older BCS, these findings have been mixed [19].…”

Protective Effects of APOE ε2 Genotype on Cognition in Older Breast Cancer Survivors: The Thinking and Living With Cancer Study

“…Our result that the APOE ε2 allele may confer protection against cognitive decline for cancer survivors selected to receive chemotherapy adds a new dimension to the body of evidence supporting a role of APOE genotype broadly and strengthens evidence suggesting parallels between CRCD and AD ( 9 , 12 , 15 , 31 , 53 ). This idea is supported by indirect evidence, including neuroimaging studies showing that breast cancer survivors and individuals with AD have abnormalities in similar brain regions ( 54 , 55 ) and overlap in the cognitive domains affected ( 9 , 56 ).…”

“…Other clinically relevant findings include the fact that similar to past studies of CRCD ( 15 ) and current models of dementia risk ( 50 ), we found that APOE genotypes do not correspond to a family history of dementia. Further, baseline mood symptoms and smoking history failed to explain the relationship between ε2 status and neuropsychological outcomes, suggesting these are distinct clinical outcomes, consistent with current multifactorial theories of CRCD ( 3 , 6 , 31 ).…”

“…We examined several potential covariates of the relationship between cognition and genotype, including sociodemographics (age, race, marital status), psychological factors (depression, anxiety), sleep (disturbed sleep yes/no based on a 2-item measure) ( 31 ), smoking history (ever vs never), and cognitive and physical reserve. Clinical depression was defined as 16 or higher on the Center for Epidemiologic Studies Depression Scale ( 32 ), and the State-Trait Anxiety Inventory State total score measured anxiety ( 33 ).…”