Better sleep hygiene may improve neurocognitive function of childhood cancer survivors

An analysis of survey data indicated that improved sleep hygiene may result in better neurocognitive outcomes for survivors of childhood cancers.

Previous research published in a 2008 issue of Sleep established that up to 20% of adult survivors of childhood cancers regularly experience fatigue, sleep disruption and daytime sleepiness. Now a multi-institutional team of investigators has determined that these conditions can have a direct effect upon survivors’ neurocognitive function, resulting in a variety of quality-of-life issues. Fatigue in the general population runs as high as 45%, according to the Sleep study.

“The novelty of the recent study is that it took an observation of the general population and extended it to cancer survivors,” Charles Sklar, MD, director of Memorial Sloan-Kettering Cancer Center’s Long-Term Follow-Up Program, told HemOnc Today. “There are reasons to think that there might be differences because cognitive functioning impairment occurs at a much higher rate in cancer survivors.”

Charles Sklar

Fatigue, neurocognitive function

“While no one functions quite as well when sleep-deprived or fatigued, most adults get by. But that is not always the case for childhood cancer survivors,” said the study’s lead investigator, Kevin Krull, PhD, of the department of epidemiology and cancer control at St. Jude Children’s Research Hospital in Memphis, Tenn., said in an interview. “Their treatments put them at a greater risk of neurocognitive dysfunction.” In particular, Krull referred to brain tumor patients who were treated with cranial radiation therapy or leukemia patients who received antimetabolite chemotherapy.

The investigators reviewed survey data collected from 1,426 participants of the NCI-sponsored Childhood Cancer Survivor Study. The control group included 384 of the survivors’ siblings. The Childhood Cancer Survivor Study includes patients who were aged 21 years or younger when diagnosed with leukemia, a central nervous system malignancy, Hodgkin’s disease, non-Hodgkin’s lymphoma, kidney cancer, neuroblastoma, a soft tissue sarcoma or bone malignancy, between 1970 and 1986, and who survived at least 5 years after diagnosis.

Using multivariate regression models, the researchers determined that more than 20% of respondents in the survivor cohort experienced impaired task efficiency related to fatigue (RR=1.34; 95% CI, 1.13-1.59); daytime sleepiness (RR=1.68; 95% CI, 1.55-1.83); poor sleep quality (RR=1.23; 95% CI, 1.01-1.49), and decreased vitality (RR=1.75; 95% CI, 1.33-2.30).

Fatigue (RR=1.77; 95% CI, 1.23-2.55), daytime sleepiness (RR=1.38; 95% CI, 1.14-1.67) and decreased vitality (RR=3.08; 95% CI, 1.98-4.79) were also predictive of emotional regulation problems. Diminished organization correlated to increased daytime sleepiness (RR=1.80; 95% CI, 1.31-2.48) and decreased vitality (RR=1.90; 95% CI, 1.37-2.63). Impaired memory was associated with poor sleep quality (RR=1.45; 95% CI, 1.19-1.76), increased sleepiness (RR=2.05; 95% CI, 1.63-2.58) and decreased vitality (RR=2.01; 95% CI, 1.42-2.86).

“The vast majority of survivors have a normal quality of life when compared to their peers and their siblings,” said Sklar. “Brain tumor survivors, however, as a group often have more psychosocial difficulties. They’re less often married, they’re more often unemployed, and when they are employed they make less money, they tend to be more socially isolated, they often are still under the care of their parents, or they live in more protected environments.”

The impact of fatigue, sleepiness, sleep quality and vitality on neurocognitive function was independent of the impact associated with cranial radiation therapy, steroids and antimetabolite chemotherapy; the results were also adjusted for sex and current age. Consistent with data reported in the Sleep study, Krull and colleagues reported that “survivors treated for Hodgkin’s lymphoma were over-represented in the current sample, given their apparently higher rates of reported fatigue and sleep problems.”

“The point is that many factors, in addition to cancer treatment, can impact cognition and memory in this population, so you need to address all of those issues if you want to get people functioning at their highest level,” Sklar said.

Improving neurocognitive function

“Results from this study highlight the importance of considering interventions to improve sleep hygiene and/or physical fitness as nonpharmacological mechanisms for improving neurocognitive functioning,” Krull and colleagues wrote. “Research suggests that the first-line interventions to improve sleep in this population should be behavioral in nature.”

One therapy that holds promise for impaired cognitive function is memory training, according to Krull, who currently is conducting a pilot study on the modality. “There are two routes to consider with this type of training,” he said. “The first is a skills-based approach. That might include some Web-based training that practices coding and retrieval of information over and over again. The other approach involves more strategy. If we can’t improve the skill, we can teach strategies such as being more organized, keeping notebooks, as ways to compensate for the memory problem.”

Kevin Krull

Exercise is a potentially effective treatment for impaired cognitive functioning caused by fatigue, Krull said. “The brain is heavily dependent on blood flow and oxygenation, and we’ve seen in some [other] studies that intensive aerobic exercise helps to improve memory function in patients who are at risk for dementia or who have early signs of dementia. So, an exercise intervention could potentially help to improve memory function in our cohort at risk for these difficulties.”

Therapies for improved sleep hygiene

Many childhood cancer survivors have difficulty falling sleep within 30 minutes, Krull said. “Improving their sleep quality might be a way to improve their neurocognitive functioning,” he said. “We would address their sleep quality by improving their sleep hygiene. Strategies [for this] include exercising before 5 PM, restricting caffeine intake to morning hours, using the bed primarily for sleeping rather than reading or watching TV, limiting daytime naps, and making sure the bedroom is dark, quiet, and at a comfortable temperature.”

“Physicians don’t always ask their patients how they are sleeping, or if they’re sleepy during the day,” said Sklar. “Those are not the typical kinds of questions we might ask of this group, but this paper would suggest that we should be paying more attention to those things, particularly in patients that are having cognitive problems.”

If patients are having fatigue or sleep problems, Krull said they may benefit from “being referred to an exercise physiologist or physical therapist who can build a safe aerobic-based exercise program for them. If they’re having sleep difficulties, then referring them to a behavioral therapist or a psychologist who can help look at sleep hygiene or other behaviors that might be interfering with their sleep onset. Respiratory problems associated with sleep difficulties should also be explored with their physician.” – Whitney McKnight

For more information:

• Clanton NR. Cancer. 2011;doi:10.1002/cncr.25797.
• Mulrooney D. Sleep. 2008;31:271-281.

Disclosure: Dr. Sklar reports he is a founding member of the Childhood Cancer Survivor Study.

Howard J. Weinstein

The Childrens Cancer Survivor Study (CCSS) continues to expand our understanding of the many factors that predispose to cancer-related morbidity and mortality. In this study, the authors showed that 20% of respondents in the survivor cohort had impaired task efficiency, emotional lability, and impaired memory in part related to poor sleep quality and fatigue. Previous research showed that sleep disturbance and daytime sleepiness persist into adulthood for childhood cancer survivors. The most recent data that these complaints are associated with neurocognitive sequelae seem to follow logically. The results of this study have already stimulated thinking about a focus on better sleep and non-pharmacologic interventions such as exercise and memory training to improve cognitive function in these young adults who have survived childhood cancer. It will also be important to determine if there is something different about the sleep of these individuals.

– Howard J. Weinstein, MD

HemOnc Today Editorial Board Member

Disclosure: Dr. Weinstein reports no relevant financial disclosures.