Brain-derived neurotrophic factor (BNDF) plays a role in synapse integrity. We investigated in 398 cognitively normal adults (60±8years, 41% female, MMSE=28±1) the joint association of the Val66Met polymorphism of the BDNF gene (Met+/-) and plasma BDNF levels and abnormal cerebrospinal fluid (CSF) amyloid-beta status (A+/-) with cognitive decline and dementia risk. Age-, sex- and education-adjusted linear mixed models showed that compared to Met-A-, Met+A+ showed steeper decline on tests of global cognition, memory, language, attention and executive functioning, while Met-A+ showed steeper decline on a smaller number of tests. There were no associations between Met+A- and cognitive decline. Cox models showed that compared to Met-A-, Met+A+ participants were at increased risk of dementia (HR=8.8, 95%CI: 2.8–27.9), as were Met-A+ participants (HR=6.5, 95%CI: 2.2–19.5). Lower plasma BDNF was associated with an increased risk of progression to dementia in the A+ participants. Our results imply that Met-carriage on top of amyloid-beta pathology might increase rate of cognitive decline to dementia.

脑源性神经营养因子 (BNDF) 在突触完整性中发挥作用。我们在 398 名认知正常的成年人（60±8 岁，41% 女性，MMSE=28±1）中调查了Val66Met的联合关联BDNF 基因多态性 (Met+/-) 和血浆 BDNF 水平和异常脑脊液 (CSF) β-淀粉样蛋白状态 (A+/-) 与认知能力下降和痴呆风险。年龄、性别和教育调整的线性混合模型显示，与 Met-A- 相比，Met+A+ 在全球认知、记忆、语言、注意力和执行功能测试中下降幅度更大，而 Met-A+ 在全球认知、记忆、语言、注意力和执行功能测试中下降幅度更大。更少的测试。Met+A-与认知能力下降之间没有关联。Cox 模型显示，与 Met-A- 相比，Met+A+ 参与者的痴呆风险增加（HR=8.8，95%CI：2.8-27.9），Met-A+ 参与者也是如此（HR=6.5, 95%CI： 2.2-19.5)。较低的血浆 BDNF 与 A+ 参与者发展为痴呆的风险增加有关。