Obesity associated with neurocognitive impairment among survivors of childhood leukemia
Overweight and obesity appeared significantly associated with neurocognitive impairment during long-term follow-up of individuals who received chemotherapy for childhood acute lymphoblastic leukemia, according to a study published in Cancer.
“We’d previously learned that patients with ALL gain weight during therapy, especially during induction, and this persists even after completion of therapy,” Hiroto Inaba, MD, PhD, faculty member in the department of oncology at St. Jude Children’s Research Hospital, told Healio. “In the general population, it has been reported that obesity affects neurocognitive function. Previously, a group [led by co-author Kevin R. Krull, PhD,] showed that [patients with ALL] develop problems in neurocognitive function. Therefore, we thought that the obesity in ALL survivors exacerbates worse neurocognitive function.”
The analysis included 210 survivors of childhood ALL treated on the St. Jude Total XV protocol — a chemotherapy-based regimen that does not include cranial irradiation — who were aged at least 8 years (median age at diagnosis, 5 years; range 3.2-8.7; 51.4% male; 73.8% white) and at least 5 years from their diagnosis. Of them, 120 were healthy/underweight, 42 had overweight and 48 had obesity.
In a cross-sectional analysis, Inaba and colleagues evaluated the association between neurocognitive function, using age-adjusted Z score, and BMI category and Z score. Due to the fluctuating nature of BMI, researchers also conducted a longitudinal analysis for which they considered being overweight or obese as an exposure, expressed using area under the curve.
The survivors had a median BMI Z score at diagnosis of 0.17, which increased to 0.54 at the end of induction and to 0.74 at the neurocognitive assessment.
Results of the cross-sectional analysis showed survivors with overweight or obesity at the time of the neurocognitive assessment scored significantly lower than healthy/underweight survivors on measures of executive function, including cognitive flexibility, planning, verbal fluency, working memory and spatial construction; attention, including attention span and risk taking; and on processing speed, including visual motor coordination, visual speed and motor speed (all P < .05).
Additionally, the longitudinal analysis — which evaluated induction, consolidation, early maintenance and late maintenance as four separate treatment periods — showed a greater AUC for overweight/obesity during induction therapy was associated with worse cognitive flexibility (P = .01) and slower motor speed (P = .02), which persisted throughout treatment. A greater AUC for overweight/obesity also negatively affected attention measures during early and late maintenance and consolidation therapy (all P < .05).
Given these findings and that obesity starts during induction therapy, early intervention should be considered, Inaba said.
“We should actively consider early intervention to decrease or prevent weight gain in [patients with ALL] and, ultimately, worse neurocognitive function,” he said.
Krull, endowed chair in cancer survivorship in the department of epidemiology and cancer control at St. Jude Children’s Research Hospital, added that inflammation and poor sleep quality previously had been associated with neurocognitive problems in ALL survivors, and he entered the study with the belief that obesity may be partially responsible for those difficulties.
“We have preliminary evidence that targeting parents to establish a healthy home lifestyle can not only improve diet and physical activity, but also decrease sedentary behavior and screen time, and improve sleep quality,” Krull told Healio.
The researchers noted the study may be limited because they did not examine obesity-related behaviors, such as physical activity and dietary patterns, which can be explored in further research.
“We have recently piloted such interventions focused on healthy home environments, and are currently planning a larger study,” Krull said.
For more information:
Hiroto Inaba, MD, PhD, can be reached at Department of Oncology, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Mail Stop 260, Memphis, TN 38105-2794; email: hiroto.inaba@stjude.org.
Kevin R. Krull, PhD, can be reached at Department of Epidemiology and Cancer Control, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Mail Stop 735, Memphis, TN 38105-2794; email: kevin.krull@stjude.org.
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