Some children who survive cancer become frail as young adults—and now, researchers have found that this condition may be associated with cognitive deficits, including impaired memory and processing speed. These findings highlight a need for interventions to preserve physical and cognitive functioning.
Some children who survive cancer become frail as young adults—and now, researchers have found that this condition is associated with cognitive deficits, including impaired memory and processing speed (J Clin Oncol 2021 Jul 20 [EPub ahead of print]). Their findings point to a need for interventions to preserve physical and cognitive functioning.
Elderly people often exhibit frailty, a sign of aging linked to dementia, Alzheimer disease, and general cognitive decline. The commonly used Fried criteria for frailty include low muscle mass, low energy expenditure, walking slowly, exhaustion, and poor grip strength. Previously, researchers established that about 8% of survivors of childhood cancer become frail in early adulthood, leaving researchers questioning whether this phenotype is also associated with neurocognitive impairments and declines in young adults who survive cancer.
Researchers evaluated 845 survivors of childhood cancer between ages 18 and 45. On average, participants were 29.7 years old and had been diagnosed with cancer 21.7 years earlier. Based on meeting three or more Fried criteria, 6.1% of survivors were classified as frail, and 18.2% were prefrail, meeting two criteria. Participants completed neurocognitive assessments at study enrollment and at periodic follow-up visits.
Initially, frail and prefrail survivors performed significantly worse than healthy survivors on tests of attention, processing speed, memory recall, cognitive flexibility, learning words, and speaking. Five years later, frail participants had declined significantly more than healthy participants on tests of short-term recall, processing speed, cognitive flexibility, and speaking. Frail and prefrail survivors also had significantly greater declines in focused attention.
“If you had this frailty phenotype, you experienced cognitive impairment … and decline over that 5-year period,” says lead author AnnaLynn Williams, PhD, of St. Jude Children's Research Hospital in Memphis, TN. “This suggests to us that this physiologic aging is also related to cognitive aging—and gives us a high-risk group to target to preserve physical and neurocognitive functioning.”
Senior author Kiri Ness, PhD, PT, also of St. Jude, adds that research is under way on physical and cognitive interventions. She and her team are also launching a trial to study pharmaceutical treatments—namely setalytic drugs that clear senescent cells. These cells, which accumulate in survivors of childhood cancer, have been linked to frailty and issues in brain function. Key, Ness says, is understanding the biological connection between frailty and cognitive decline. “Then you can develop the best combination of behavioral and pharmaceutical interventions.”
“It's really important research. To my knowledge this is the first paper that shows the connection between frailty and cognitive deficits in younger people,” says Jennifer Schrack, PhD, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, MD, who was not involved in the work.
Schrack wants to know more about the relationship between treatment and the risk of becoming frail and developing cognitive deficits. “It's kind of like a million-dollar question,” she says, because the answer could inform treatment—especially when multiple therapies are available. She also wonders what other factors, such as treatment duration and cancer type, affect risk.
The study's results reinforce the need to continue following and caring for these patients. “Survivorship doesn't end when cancer ends,” she says. “It's a lifelong process that needs to be monitored and better understood.” –Catherine Caruso
For more news on cancer research, visit Cancer Discovery online at http://cancerdiscovery.aacrjournals.org/CDNews.