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.
Highlights
Alzheimer’s disease (AD) is the sixth leading cause of death in the United States and is the most prevalent dementia worldwide, with approximately 50–60% of all the dementia cases amongst elderly over 65 years old attributed to AD [1,2,3]
Fifteen out of the 19 studies provided sufficient data to allow for the comparison of the serum brain-derived neurotrophic factor (BDNF) levels between AD and healthy control groups (Table 1)
The analyses identified the important factors that contributed to the observed heterogeneity in serum BDNF levels in the studies reviewed, which necessitates controlling for these factors in future studies
Summary
Alzheimer’s disease (AD) is the sixth leading cause of death in the United States and is the most prevalent dementia worldwide, with approximately 50–60% of all the dementia cases amongst elderly over 65 years old attributed to AD [1,2,3]. There are approximately 36 million people suffering from AD or other types of dementia, and the number of patients with dementia was predicted to reach 80 million by 2050 worldwide [4]. BDNF plays a prominent role in modulating cognition and memory. The expression of the BDNF gene can be found in the cortex, hippocampus, and basal forebrain regions that are indispensable for memory, learning, and higher cognitive function. Weinstein et al found that higher peripheral BDNF levels protect the older adults against AD. By having BDNF levels higher by one standard deviation, the risk for AD or dementia was lowered by 33% [9]
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