Associations of Weight Sensitive Cytokine Concentration Changes with Neurodegeneration in the Look AHEAD Cohort

ABSTRACT Objective We explore associations that four weight-sensitive and neuroactive cytokines – adiponectin, leptin, interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF) – have with cross-sectional brain volumes among adults with obesity or overweight and with type 2 diabetes (T2D). Methods Cytokine concentrations were assayed at baseline and proximal to the end of two 10-year lifestyle interventions among 233 Look AHEAD trial participants. Magnetic resonance imaging measured total, white, and gray matter brain volumes. Associations that cytokine concentrations and changes in concentrations had with brain volumes and weight changes were assessed. Results Higher IL-6 and VEGF concentrations were associated with smaller total brain volumes (β=-3.00 [95% CI -14.82,-3.07] and β=-2.79 [-10.08,-1.74] log-units/cc respectively). Higher leptin concentrations were associated with higher white matter volumes (β=2.00 [-0.06,6.92] log-units/cc). Increases in adiponectin were associated with greater total brain volumes (β=2.14 [0.50,11.94] log-units/cc). Higher leptin and IL-6 concentrations were associated cross-sectionally with greater body mass index (BMI) and increases in leptin, IL-6, and VEGF concentrations were associated with increases in BMI. Neither lifestyle intervention nor changes in BMI materially affected associations between cytokines and brain volumes. Conclusions Weight-sensitive neuroactive cytokine concentrations are related to brain volumes. Weight changes and lifestyle interventions targeting weight loss may not materially influence these associations in adults with T2D.