Serum brain-derived neurotrophic factor mediates the relationship between abdominal adiposity and executive function in middle age

Objectives: Excessive adipose tissue, especially in the abdominal area, is associated with increased risk of dementia in older adults. However, the mechanisms underlying this relationship are poorly understood. As increased adiposity is also associated with lower circulating levels of brain-derived neurotrophic factor (BDNF), a key molecule modulating brain plasticity and neuronal regeneration, we hypothesized that the changes in cognition that occur as a result of excessive abdominal adiposity would be driven by lower levels of circulating BDNF. Methods: Fasting blood samples were obtained from 60 participants aged 40-60 years (mean±SD=52.3±5.6) and BDNF levels were assessed with an enzyme linked immunosorbent assay. Abdominal adiposity was measured using a ratio of waist circumference to hip circumference (WHR). Participants also completed a neuropsychological assessment battery to assess executive function. Statistical mediation was assessed using traditional causal steps and nonparametric bootstrapping. Results: Higher WHR was significantly associated with poorer performance on the Controlled Oral Word Association (COWA) letter fluency test (β=-0.489; p=.003) and lower levels of circulating BDNF (β=-0.345; p=.006). Linear regression and bootstrapping methods indicated that BDNF fully mediated the relationship between WHR and performance on the COWA (β=0.60; 95% confidence interval [-3.79, -0.26]). Conclusions: The relationship between higher WHR and verbal fluency was fully statistically mediated by circulating BDNF levels. The BDNF pathway is thus a useful probable mechanism through which executive function decline occurs in individuals with high abdominal adiposity. BDNF enhancing interventions (physical exercise and dietary restriction) could thus be used to improve executive function in these individuals.