Effects of Brain Derived Neurotrophic Factor on White Matter Integrity in Middle-Aged Adults: A Voxel-Based Diffusion Tensor Imaging Study (S39.006)

Objective: To relate circulating Brain Derived Neurotrophic Factor (BDNF) levels to measures of Fractional Anisotropy (FA) using Diffusion Tensor Imaging (DTI) in the Framingham Heart Study (FHS) Offspring cohort. Background: Previous work from FHS has related higher serum BDNF concentration with decreased risk of incident stroke and dementia and lower white matter hyperintensity burden. BDNF is also inducible by exercise, social contact and caloric restriction, factors that promote cognitive reserve. We now explore the spatial distribution of subtle white matter (WM) injury associated with serum BDNF and whether integrity of implicated tracts may relate with cognitive performance in domains previously associated with vascular risk factors and vascular brain injury. Methods: In 577 FHS Offspring (mean age 58.9±8.1 yrs; 40.9[percnt] W), we related, at voxel level, FA measures derived from DTI to BDNF levels using multivariate linear regression, adjusting for age, gender, intracranial volume (ICV) and time between clinical and MRI exams (Δt). We then used generalized linear models to relate integrity of tracts implicated in BDNF associations with performance in visuospatial memory and executive function domains, adjusting for age, gender, ICV, Δt and education. Results: Greater BDNF was independently associated with higher FA in voxels that covered 44 cc of the WM. WM tracts showing the most benefit included the corpus callosum (9.4cc) and the corona radiata (8.2cc). Preserved integrity of BDNF-related WM tracts, was also associated with better executive function, including in the superior longitudinal fasciculus (3.0 cc, p<0.05). Conclusions: In our community-based, stroke-free middle-aged sample, elevated BDNF has a subtle, positive effect on WM microstructural integrity in specific tracts whose integrity was also found to be associated with preserved executive function. These data can expand our understanding of the structural pathways in the brain implicated in BDNF mediated preservation of cognitive reserve and protection from vascular brain injury. Disclosure: Dr. Maillard has nothing to disclose. Dr. Satizabal has nothing to disclose. Dr. Beiser has nothing to disclose. Dr. Himali has nothing to disclose. Dr. Chen has nothing to disclose. Dr. Vasan has nothing to disclose. Dr. Seshadri has nothing to disclose. Dr. DeCarli has nothing to disclose.