Plasma BDNF Is Associated with Age-Related White Matter Atrophy but Not with Cognitive Function in Older, Non-Demented Adults

Ira Driscoll,Yang An,Luigi Ferrucci,Bronwen Martin,Stuart Maudsley,Mark P Mattson,Susan M Resnick,Kenji Hashimoto

doi:10.1371/journal.pone.0035217

Abstract

Brain derived neurotrophic factor (BDNF) seems to be involved in regulation of synaptic plasticity and neurogenesis. BDNF plasma and serum levels have been associated with depression, Alzheimer's disease, and other psychiatric and neurodegenerative disorders. In a community sample, drawn from the Baltimore Longitudinal Study of Aging (BLSA), we examined whether BDNF plasma concentration was associated with rates of age-related change in cognitive performance (n = 429) and regional brain volume (n = 59). Plasma BDNF levels, which were significantly higher in females (p<0.05), were not associated with either concurrent cognitive performance or rates of age-related change in performance across cognitive domains (p's>0.05). Sex differences in the relationship between BDNF and the trajectories of regional brain volume changes were observed for the whole brain and frontal white matter volumes (p<0.05), whereby lower plasma BDNF was associated with steeper volume decline in females but not males. Together, our findings contribute to furthering the understanding of the relationships between plasma BDNF, structural brain integrity and cognition. Potential mechanisms mediating these relationships merit further investigation.

Highlights

Alzheimer’s disease (AD) is a fatal neurodegenerative disorder characterized by the progressive loss of both grey and white matter, and cognitive impairment
Our results are in accord with the existing literature reporting lower serum and plasma brain-derived neurotrophic factor (BDNF) levels with increasing age [12,15,16], with significantly higher levels observed in women compared to men [12,16,17,18]
We found that lower plasma BDNF was associated with steeper rates of age-related regional brain volume atrophy

Summary

Introduction

Alzheimer’s disease (AD) is a fatal neurodegenerative disorder characterized by the progressive loss of both grey and white matter, and cognitive impairment. Reduced BDNF levels in various brain regions have been implicated in the pathogenesis of neurodegenerative and psychiatric disorders [2]. Val66Met has been related to smaller hippocampal volumes [3,5,6] , which in turn are associated with worse memory [7] and more rapid conversion to dementia [8]. The mechanisms underlying these BDNF associations with brain function and structure, remain unclear

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