Increased Plasma brain‐derived neurotrophic factor (BDNF) as a Biomarker for Differentiating Mild Cognitive Impairment from Cognitive Healthy: A case‐control study

Abstract

AbstractBackgroundAcross the spectrum of Alzheimer’s disease (AD), we previously conducted a meta‐analysis and concluded significantly decreased brain‐derived neurotrophic factor (BDNF) in AD. However, there are inconsistent findings on peripheral BDNF levels in mild cognitive impairment (MCI), even across different meta‐analyses, which have been attributed to the high heterogeneity caused by multiple clinical and laboratory factors. Thus, BDNF’s discriminative accuracy for identifying all‐cause MCI and its subtypes remains unknown.MethodsThis study, while accounting for heterogeneity, compared a healthy control cohort (n=56, 45 female) and an MCI cohort (n=40, 28 female) to determine whether plasma BDNF (pBDNF), hs‐CRP, and DHEA‐S can differentiate between healthy and MCI individuals, including the two MCI subtypes (amnestic [aMCI] and non‐amnestic [non‐aMCI]). Furthermore, the associations between the biomarkers and detailed neurocognitive tests were examined. Adults with cerebral palsy were included as sensitivity analyses.ResultCompared to healthy controls, only pBDNF was significantly increased in all‐cause MCI, aMCI, and non‐aMCI. Furthermore, pBDNF had good (AUC=0.84, 95% CI=0.74 to 0.95, p<0.001) and excellent discriminative accuracy (AUC=0.92, 95% CI=0.84 to 1.00, p<0.001) for all‐cause MCI and non‐amnestic MCI, respectively. pBDNF was also significantly and positively associated with plasma hs‐CRP (β=0.26, 95% CI=0.02 to 0.50, p=0.038), despite attenuated association upon controlling for BMI (β=0.15, 95% CI=‐0.08 to 0.38, p=0.186). Multiple associations with detailed neurocognitive tests were observed.ConclusionThese findings support increased pBDNF as a compensatory mechanism in preclinical dementia, and the neurotrophic and inflammatory hypotheses of cognitive impairment.