Disrupted Sleep Impairs Cognition in Childhood Cancer Survivors

Kevin R. Krull, PhD

According to the results of a recent study, fatigue and sleep disruption reduce neurocognitive function in adult survivors of childhood cancer. The study’s investigators said that while prior research has focused on the “direct insults” associated with cancer treatment, their findings point to the additive role of less direct pathways, such as poor sleep and fatigue. Nancy R. Clanton, PhD, with St. Jude Children’s Research Hospital in Memphis, Tennessee, and colleagues examined the links between neurocognitive function and fatigue and sleep in 1426 childhood cancer survivors and 384 healthy siblings.

The authors pointed out that long-term survivors of childhood cancer are known to be at risk for fatigue and sleep disruptions. For example, as many as 45% of the general population report fatigue versus up to 90% of cancer survivors. Survivors of childhood cancer are also known to be at increased risk for neurocognitive impairment either directly or indirectly from central nervous system (CNS) treatment. Cranial irradiation has long been linked to neurocognitive late effects, and antimetabolite chemotherapy and corticosteroids have been reported to worsen outcomes.

Before the present study, the association between sleep, fatigue, and neurocognitive impairment in long-term survivors of childhood cancer had not been examined.

Neurocognitive deficits can severely impair quality of life, and the results suggest that adult survivors of childhood cancer may benefit from memory training.

—Kevin R. Krull, PhD

Participants were enrolled in the ongoing Childhood Cancer Survivor Study. The retrospective cohort study is tracking the longterm medical, psychosocial, and functional outcomes of individuals who were treated for 1 of 8 childhood cancers between 1970 and 1986, who were aged <21 years, and who survived for at least 5 years after their initial diagnosis. The study also includes siblings of some of the survivors who serve as comparator controls.

The present analysis found that more than 20% of survivors had neurocognitive impairment on the Neurocognitive Questionnaire. The 25-item, patient-completed questionnaire examines 4 primary factors of neurocognitive outcome, including task efficiency, emotion regulation, organization, and memory, and has been previously validated in adult survivors of childhood cancer. Impaired cognition was defined as a score below the 10th percentile based on the norms for siblings that were adjusted for age and sex. Survivors of CNS tumors had the highest rates of neurocognitive difficulties. Task efficiency was impaired in 43% of this subgroup, emotion regulation in 13%, organization in 21%, and memory in 23%.

The analysis also showed that while cancer survivors had only nominally higher rates of sleep disturbance than their healthy siblings, cancer survivors had a three- to four-fold higher risk of cognitive disturbances when they reported higher fatigue, poor sleep quality, daytime sleepiness, and low vitality. What’s more, Clanton and associates said the relative risk for neurocognitive impairment associated with fatigue and sleep disturbance was similar to that occurring with high-dose radiation.

Survivors who said they used antidepressants had a 70% (P <.0001) higher risk of memory problems and a 56% (P <.0001) higher risk of reduced task efficiency. Notably, the adverse effects of fatigue, sleepiness, sleep quality, and vitality on neurocognitive outcomes were independent of the effects of cranial radiation therapy, steroids and antimetabolite chemotherapy, sex, and current age.

Study co-author Kevin R. Krull, PhD, also with St. Jude Children’s Research Hospital, said in a news release that neurocognitive deficits can severely impair quality of life, and that the results suggest that adult survivors of childhood cancer may benefit from memory training. Periodic screening for the fatigue and sleep disturbances that are often responsible for impairments in memory and other neurocognitive functions may also be helpful.

Clanton NR, Klosky JL, Li C, et al. Fatigue, vitality, sleep, and neurocognitive functioning in adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study [published online ahead of print April 11, 2011]. Cancer. doi: 10.1002/cncr.25797.