Abstract
Background: Previous meta-analyses examining the continuum of Alzheimer’s disease (AD) concluded significantly decreased peripheral brain-derived neurotrophic factor (BDNF) in AD. However, across different meta-analyses, there remain inconsistent findings on peripheral BDNF levels in individuals with mild cognitive impairment (MCI). This issue has been attributed to the highly heterogenous clinical and laboratory factors. Thus, BDNF’s level, discriminative accuracy for identifying all-cause MCI and its subtypes, and its associations with other biomarkers and neurocognitive domains, remain largely unknown.Methods: To address this heterogeneity, we compared a healthy control cohort (n=56, 45 female) to an MCI cohort (n=40, 28 female), to determine whether plasma BDNF, hs-CRP, and DHEA-S can differentiate healthy from MCI individuals, including two MCI subtypes (amnestic [aMCI] and non-amnestic [non-aMCI]). The associations between BDNF with other biomarkers and neurocognitive tests were examined. Adults with cerebral palsy were included as sensitivity analyses.Results: Compared to healthy controls, BDNF was significantly higher in all-cause MCI, aMCI, and non-aMCI. Furthermore, BDNF had good (AUC=0.84, 95% CI=0.74 to 0.95, p<0.001) and excellent discriminative accuracies (AUC=0.92, 95% CI=0.84 to 1.00, p<0.001) for all-cause MCI and non-amnestic MCI, respectively. BDNF was 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 inverse associations between BDNF and detailed neurocognitive tests were also detected.Conclusions: These findings suggest BDNF is increased as a compensatory mechanism in preclinical dementia, supporting the neurotrophic and partially the inflammatory hypotheses of cognitive impairment.
Highlights
Mild cognitive impairment (MCI) is an intermediate state between normal aging and early dementia [1,2,3]
Addressing the clinical and laboratory heterogeneity causal of the contradictory evidence present in the literature, we found plasma brain-derived neurotrophic factor (BDNF) to be significantly higher in mild cognitive impairment (MCI), compared to healthy control (HC)
Its discriminative accuracy for aMCI was poorer compared to those of total MCI and non-aMCI. These findings remained unchanged upon performing sensitivity analyses that excluded cases with co-morbid major depressive disorder (MDD) and generalized anxiety disorder (GAD), and sensitivity analyses with cerebral palsy (CP)
Summary
Mild cognitive impairment (MCI) is an intermediate state between normal aging and early dementia [1,2,3]. A biomarker has several advantages in screening and triaging a clinical diagnosis; in addition to being less time-consuming than administering a comprehensive battery of neurocognitive tests, it serves as an objective measure free from the influence of interviewer and patient bias. Across different meta-analyses, there remain inconsistent findings on peripheral BDNF levels in individuals with mild cognitive impairment (MCI). This issue has been attributed to the highly heterogenous clinical and laboratory factors. BDNF’s level, discriminative accuracy for identifying all-cause MCI and its subtypes, and its associations with other biomarkers and neurocognitive domains, remain largely unknown. Conclusions: These findings suggest BDNF is increased as a compensatory mechanism in preclinical dementia, supporting the neurotrophic and partially the inflammatory hypotheses of cognitive impairment
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