先前对阿尔茨海默病(AD)的连续性进行的荟萃分析得出结论,AD中的外周脑源性神经营养因子(BDNF)显着降低。然而,在不同的荟萃分析中,轻度认知障碍(MCI)患者外周BDNF水平的研究结果不一致.这个问题归因于高度异质性的临床和实验室因素。因此,BDNF的水平,识别全因MCI及其亚型的判别准确性,以及它与其他生物标志物和神经认知领域的关联,基本上是未知的。
为了解决这种异质性,我们比较了健康对照队列(n=56,45女性)和MCI队列(n=40,28女性),为了确定血浆BDNF,hs-CRP,DHEA-S可以区分健康个体和MCI个体,包括两种MCI亚型(遗忘型[aMCI]和非遗忘型[非aMCI])。研究了BDNF与其他生物标志物和神经认知测试之间的关联。纳入脑瘫成人作为敏感性分析。
与健康对照相比,BDNF在全因MCI、aMCI和非aMCI中显著增高。此外,BDNF对全因MCI和非遗忘型MCI具有良好的鉴别准确性(AUC=0.84,95%CI=0.74至0.95,p<0.001)和出色的鉴别准确性(AUC=0.92,95%CI=0.84至1.00,p<0.001)。BDNF与血浆hs-CRP呈显著正相关(β=0.26,95%CI=0.02~0.50,p=0.038),尽管在控制BMI时相关性减弱(β=0.15,95%CI=-0.08至0.38,p=0.186)。还检测到BDNF和详细的神经认知测试之间的多个逆关联。
这些研究结果表明,BDNF在临床前痴呆中作为一种代偿机制增加,支持认知障碍的神经营养和部分炎症假说。
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.
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.
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.
These findings suggest BDNF is increased as a compensatory mechanism in preclinical dementia, supporting the neurotrophic and partially the inflammatory hypotheses of cognitive impairment.