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Meta-Analysis
. 2019 Jan 10;20(2):257.
doi: 10.3390/ijms20020257.

Decreased Serum Brain-Derived Neurotrophic Factor (BDNF) Levels in Patients with Alzheimer's Disease (AD): A Systematic Review and Meta-Analysis

Ted Kheng Siang Ng  1 , Cyrus Su Hui Ho  2   3 , Wilson Wai San Tam  4 , Ee Heok Kua  5   6 , Roger Chun-Man Ho  7   8   9   10   11
Affiliations
Meta-Analysis

Decreased Serum Brain-Derived Neurotrophic Factor (BDNF) Levels in Patients with Alzheimer's Disease (AD): A Systematic Review and Meta-Analysis

Ted Kheng Siang Ng et al. Int J Mol Sci. .

Abstract

Findings from previous studies reporting the levels of serum brain-derived neurotrophic factor (BDNF) in patients with Alzheimer's disease (AD) and individuals with mild cognitive impairment (MCI) have been conflicting. Hence, we performed a meta-analysis to examine the aggregate levels of serum BDNF in patients with AD and individuals with MCI, in comparison with healthy controls. Fifteen studies were included for the comparison between AD and healthy control (HC) (n = 2067). Serum BDNF levels were significantly lower in patients with AD (SMD: -0.282; 95% confidence interval [CI]: -0.535 to -0.028; significant heterogeneity: I² = 83.962). Meta-regression identified age (p < 0.001) and MMSE scores (p < 0.001) to be the significant moderators that could explain the heterogeneity in findings in these studies. Additionally, there were no significant differences in serum BDNF levels between patients with AD and MCI (eight studies, n = 906) and between MCI and HC (nine studies, n = 5090). In all, patients with AD, but not MCI, have significantly lower serum BDNF levels compared to healthy controls. This meta-analysis confirmed the direction of change in serum BDNF levels in dementia. This finding suggests that a significant change in peripheral BDNF levels can only be detected at the late stage of the dementia spectrum. Molecular mechanisms, implications on interventional trials, and future directions for studies examining BDNF in dementia were discussed.

Keywords: Alzheimer’s disease; BDNF; cognition; meta-analysis; meta-regression; mild cognitive impairment; systematic review.

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Conflict of interest statement

The authors declare no conflict of interests.

Figures

Figure 1
Figure 1
PRISMA diagram describing the process of study selection.
Figure 2
Figure 2
Meta-analysis of serum BDNF levels between AD, MCI, and healthy controls (HC). (A) Forest plots depicting the standardized mean differences of serum BDNF levels of patients with AD compared to healthy controls; (B) Forest plots depicting the standardized mean differences of serum BDNF levels of individuals with MCI compared to AD; (C) Forest plots depicting the standardized mean differences of serum BDNF levels of individuals with healthy controls compared to MCI.
Figure 2
Figure 2
Meta-analysis of serum BDNF levels between AD, MCI, and healthy controls (HC). (A) Forest plots depicting the standardized mean differences of serum BDNF levels of patients with AD compared to healthy controls; (B) Forest plots depicting the standardized mean differences of serum BDNF levels of individuals with MCI compared to AD; (C) Forest plots depicting the standardized mean differences of serum BDNF levels of individuals with healthy controls compared to MCI.
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