Serum proBDNF availability predicts memory gains in the FINGER multimodal lifestyle intervention

Abstract

AbstractBackgroundBrain‐derived neurotrophic factor (BDNF), including the mature form (mBDNF) and its precursor (proBDNF), has an important role in synaptogenesis, and is possibly also involved in pathophysiological mechanisms related to dementia. In this study we relate, for the first time, serum levels of both mBDNF and proBDNF with cognitive changes in elderly persons at risk of dementia during a multimodal life‐style intervention.MethodParticipants from the Finnish Geriatric Intervention Study to prevent cognitive impairment and disability (FINGER) were included in the analysis. BDNF and proBDNF levels were measured in serum of a subsample of 151 participants, aged between 60 and 79 years, with high compliance to the intervention protocol. The multidomain intervention comprised a combination of lifestyle changes (diet, exercise, cognitive training, and vascular risk management) over 24 months. Cognitive assessments were performed at baseline, after 12 months and after 24 months. BDNF levels and changes in BDNF levels were related to changes in overall cognitive performance and to changes in three cognitive domains over the intervention period through multiple linear regression models.ResultWe found a positive association between proBDNF levels, and improved memory performance after the FINGER intervention. This association was especially strong for changes in complex memory performance (B=0.84, 95% confidence interval (CI): 0.42 – 1.26, p=0.0001), suggesting that proBDNF availability can serve as a powerful predictor of memory benefits from lifestyle changes of the type that were implemented in the FINGER study. In this respect, proBDNF outperformed mBDNF, where no associations to cognition was seen, and all other investigated predictors, including age, sex, education, and ApoE4 status. Average levels of mBDNF and proBDNF did not change during the course of the intervention, but participants with larger increases in their proBDNF levels also had larger gains in memory performance.ConclusionThese results suggest that circulating proBDNF is a key factor in the molecular processes underlying memory improvement.