Reduced physiological reserve and a blunted response to acute exercise in adults with cerebral palsy

Abstract

Cerebral palsy (CP) is an early-onset neurodevelopmental condition associated with metabolic impairment and an increased risk of non-communicable diseases across the lifespan. However, the basis of these changes remains largely unknown. This study provides a comprehensive cardiometabolic and physical function profile of 23 adults with CP relative to 33 typically developing (TD) adolescents and 61 TD adults. Compared to TD individuals, adults with CP exhibited reduced cardiorespiratory fitness, smaller cardiac dimensions, and lower muscle mass. Circulating metabolomic and proteomic profiling identified a distinct molecular signature in CP, including altered tricarboxylic acid (TCA) cycle metabolites, and elevated myostatin, matrix-related proteins and pro-inflammatory cytokines. We further tested the capacity for physiological and molecular adaptation using an acute bout of endurance exercise. In response to exercise, individuals with CP exhibited an attenuated response compared to TD groups, characterized by a blunted lactate response and lower venous oxygen levels. TD participants also increased canonical exercise-responsive factors, including NADK, IL-8, ANGPTL1 and GDF15, whereas these responses were attenuated in CP. These novel findings define a distinct cardiometabolic profile in adults with CP at rest and reveal an attenuated molecular response to exercise. These data carry implications for targeted interventions and prevention strategies across the lifespan.