Cardiopulmonary Fitness and Neurocognitive Function in Long-term Childhood Hodgkin Lymphoma Survivors

Survivors of childhood Hodgkin lymphoma (HL) are at risk of cardiopulmonary morbidity, which can affect physical fitness and neurocognitive outcomes. This cross-sectional analysis examined whether poor cardiopulmonary fitness is associated with neurocognitive impairment. Aerobic fitness tests (METs) and neuropsychological assessments of executive function, working memory, intelligence, academic skills, attention, and processing speed were conducted in 204 adult HL survivors and 205 age-, sex-, and race/ethnicity-matched controls. The participants completed health and behavioral questionnaires. The medical records were abstracted for treatment history. Sex-stratified multivariable modeling was used to test the association between METs and age-adjusted neuropsychological scores. Covariates included age at diagnosis, tobacco smoking status, cumulative doses of chest and neck radiation, anthracyclines, bleomycin, and systemic methotrexate. Survivors (mean [SD] age 36.6 [8.0] years had lower exercise tolerance (7.7 vs 8.7 METs; p=0.01) than controls (age 36.8 [9.2] years). Female survivors achieved lower METs than did male survivors (6.8 vs 8.8 METs; p<0.01). In female survivors, each 1-MET increase in exercise tolerance was associated with better visual (β=0.18, p<0.01) and visuomotor processing speeds (β=0.18, p<0.01) and sustained attention (β=0.16, p<0.01). No such associations were found among the male survivors. Significant interactions were observed between METs and hypogonadism in female survivors. Higher fitness may have attenuated the motor processing speed deficits associated with estrogen deficiency (β=0.32, p=0.02). Cardiopulmonary fitness appears to be more strongly associated with neurocognitive health among female survivors of HL. These findings suggest that neurocognitive interventions for survivors could be tailored to include aerobic rehabilitation, particularly for female survivors.