Healthy lifestyles: mitigating the risk of cognitive impairment in childhood cancer survivors

As we age, all people naturally experience some cognitive decline in processing speed, memory and executive function. For example, parents confronted with math homework from their children often struggle to recall how to apply equations that were once second nature. Lawyers, with once-sharp memories of decades of case history, begin forgetting critical details in the heat of the moment during a trial. This experience, a slow leak rather than a bursting dam of decline in cognitive skills, begins in the late 20s and continues throughout life. The rate of decline is negligible in most people, not affecting their lives until near retirement age. However, certain populations, such as childhood cancer survivors, appear to be more vulnerable to an accelerated rate of decline.

“We’re all going to have some cognitive decline as we age,” said Nicholas Phillips, MD, PhD, St. Jude Department of Epidemiology and Cancer Control, “primarily in the domain of processing speed, which is why you just can’t beat a 13-year-old kid playing video games like Fortnite as an adult.”

“We found that survivors are at a higher risk of neurocognitive decline over their entire life span,” Phillips continued. “We should really be surveilling them throughout their life to ensure they’re not having these neurocognitive declines faster than we would expect in the normal population.”

Current recommendations for surveilling survivors are based on the type of treatment they received, suggesting baseline neurocognitive exams for children only early in survivorship — for five years after diagnosis or after completing therapy (typically if chemotherapy or radiation that was administered targeted the brain). New St. Jude research, led by Phillips (first and corresponding author) and published in JAMA Network Open, suggests that physicians should extend surveillance, because it is possible for those without significant neurocognitive decline 5 to 10 years after treatment to begin experiencing an accelerated decline 15 years or more after treatment when compared to their siblings. The research also shows that avoiding smoking and other modifiable lifestyle factors can decrease the risk of decline.

Understanding the rate of neurocognitive decline

“Neurocognitive decline is a loss of previously attained cognitive functions,” said senior author Kevin Krull, PhD, St. Jude Department of Psychology and Biobehavioral Science chair. “For example, if a person was operating at a level of good memory function so that they did their job well, but then they’re no longer capable of that level of performance — these survivors have likely lost critical skills.”

“To clarify, these individuals gain the skills at a level that was commensurate with their peers,” Krull said. “The difference is that they have declined from that previous level of functioning through a loss of memory or ability to process information as they did in years prior.”

The data demonstrate that these survivors are two to four times more likely to experience neurocognitive decline than their siblings of a similar age 15 years after treatment, despite having no signs of impairment 5 to 10 years after being cured of their cancer. Often in their 30s and 40s, they appear to experience a cognitive decline usually associated with older age (i.e., 60s and 70s). This historical cohort, treated between 1970 and 1986, completed a baseline neurocognitive assessment in 2003-2004 and a follow-up neurocognitive assessment in 2014-2015.

“This survivor population, who didn’t have memory problems, suddenly has memory problems at thirty years old,” Phillips explained. “They’re so far removed from treatment that seeing this new onset was surprising.”

Survivors were assessed using a neurocognitive questionnaire developed by Krull. It can be deployed in minutes, making it simple to integrate into primary care. The St. Jude study suggests that educating survivors, their families and primary care providers on how to measure neurocognitive decline with easy-to-use tools, such as the questionnaire, and how to prevent these outcomes could help manage long-term risks.

Healthy lifestyles help mitigate neurocognitive risks

The good news is that some factors associated with late-onset health problems appear modifiable. Lifestyle choices such as abstaining from smoking or vaping, staying physically active and maintaining a healthy body mass index (BMI) were associated with a decreased risk of neurocognitive decline in these long-term survivors.

“Never ever start smoking,” Phillips said. “We also found that maintaining physical activity was a huge predictor of preserved neurocognitive functions later in life, as is managing BMI.”

“We’re now trying to implement those healthy behaviors at an earlier time, working with psychologists introducing healthy lifestyles as patients conclude their cancer therapy,” Krull said. “We want to start early because increasing physical activity and reducing sedentary behaviors is difficult and can be a struggle for adults.”

“It’s a familiar story around New Year’s resolutions that people join the gym and use it for three or four months but then stop, then they’re paying for a gym membership they don’t use for the rest of the year. Adult survivors go through the same struggle,” Krull explained. “We want to establish healthy behaviors during childhood and adolescence that continue into adulthood as a proactive preventative measure.”

Finding neurocognitive risk in an unexpected place

The study shed some light on the connections between the type of cancer a patient was treated for as a child and neurocognitive decline. There is an association between patients treated for central nervous system (CNS) tumors, acute lymphoblastic leukemia (ALL) and Hodgkin’s lymphoma with an increased risk of neurocognitive decline.

“We were a little surprised that the patients who did not receive chemotherapies or radiation directed at the CNS, like Hodgkin lymphoma survivors, reported higher levels of memory impairment than their siblings,” Phillips said. “We’ve now identified new at-risk populations whose neurocognitive problems may have gotten lost in the shuffle without this study.”

“Historically, these patients have complained of memory problems,” Phillips described. “But St. Jude is one of the only places to have been looking at how cancer treatment as a child affects what happens fifteen years out, so I think this has been a huge surprise to the general community.”

These findings indicate that other factors, such as chemotherapy treatments, or health challenges that develop later in life, such as cardiovascular problems, contribute and interact to influence cognitive impairment. The study represents an early foray into these complex relationships. But now that researchers and clinicians know to look for these mechanisms in a much broader context, they can better understand the scope of the problem and how to help survivors.

Surveillance and lifestyle right now

Future work will identify and address the mechanisms underlying increased neurocognitive decline. For now, the St. Jude study joins a growing body of work emphasizing the importance of continued surveillance and promoting healthy lifestyle choices in preserving survivors’ cognitive function.

“We have pretty simple take home messages for survivors,” Phillips concluded. “Don't smoke. Stay physically active. Take care of yourself. And sleep well.”