German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Germany.
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
J Alzheimers Dis. 2022;88(1):311-322. doi: 10.3233/JAD-220356.
Insulin-like growth factor 1 (IGF-1) signaling has been implicated in Alzheimer's disease pathogenesis, and further evidence suggests inflammation can be a moderator of this association. However, most research to date has been conducted on older adults.
To investigate the association of serum IGF-1 and IGF binding protein 3 (IGFBP-3) concentrations with MRI markers of Alzheimer's disease in predominantly middle-aged adults, and further assess moderation by chronic inflammation.
We included participants from the Framingham Heart Study (n = 1,852, mean age 46±8, 46% men) and the Study of Health in Pomerania (n = 674, mean age 50±13, 42% men) with available serum IGF-1, IFGBP-3, as well as brain MRI. IGF-1 and IFGBP-3 were related to MRI outcomes (i.e., total brain, cortical gray matter, white matter, white matter hyperintensities (WMH), and hippocampal volumes) using multivariable regression models adjusting for potential confounders. Subgroup analyses by C-reactive protein (CRP) concentrations were also performed. Cohort-specific summary statistics were meta-analyzed using random-effects models and corrected for multiple comparisons.
Meta-analysis results revealed that higher IGF-1 concentrations were associated with lower WMH (estimate [β] [95% CI], -0.05 [-0.09, -0.02], p = 0.006) and larger hippocampal volumes (0.07 [0.02, 0.12], p = 0.01), independent of vascular risk factors. These associations occurred predominantly in individuals with CRP concentrations < 75th percentile. We did not observe associations between IGFBP-3 and MRI outcomes.
Our findings suggest that IGF-1-related signaling may be implicated in brain health as early as midlife.
胰岛素样生长因子 1（IGF-1）信号在阿尔茨海默病发病机制中起作用，进一步的证据表明炎症可以调节这种关联。然而，迄今为止，大多数研究都是在老年人中进行的。
在以中年人为主体的人群中，研究血清 IGF-1 和 IGF 结合蛋白 3（IGFBP-3）浓度与阿尔茨海默病 MRI 标志物之间的关联，并进一步评估慢性炎症的调节作用。
我们纳入了弗雷明汉心脏研究（Framingham Heart Study，n = 1852，平均年龄 46±8 岁，46%为男性）和波罗的海健康研究（Study of Health in Pomerania，n = 674，平均年龄 50±13 岁，42%为男性）中可用的血清 IGF-1、IGFBP-3 以及脑 MRI 数据。使用多变量回归模型，调整潜在混杂因素后，IGF-1 和 IGFBP-3 与 MRI 结果（即总脑、皮质灰质、白质、白质高信号（WMH）和海马体积）相关。还按 C 反应蛋白（C-reactive protein，CRP）浓度进行了亚组分析。使用随机效应模型对队列特异性汇总统计数据进行荟萃分析，并校正多重比较。
荟萃分析结果表明，较高的 IGF-1 浓度与较低的 WMH（估计值 [β] [95%置信区间]，-0.05 [-0.09，-0.02]，p = 0.006）和较大的海马体积（0.07 [0.02，0.12]，p = 0.01）相关，独立于血管危险因素。这些关联主要发生在 CRP 浓度<75 百分位数的个体中。我们没有观察到 IGFBP-3 与 MRI 结果之间的关联。
我们的研究结果表明，IGF-1 相关信号可能早在中年就与大脑健康有关。
