Pappas Colleen, Bauer Christopher E, Zachariou Valentinos, Libecap T J, Rodolpho Beatriz, Sudduth Tiffany L, Nelson Peter T, Jicha Gregory A, Hartz Anika Ms, Shao Xingfeng, Wang Danny J J, Gold Brian T
Department of Neuroscience, College of Medicine, University of Kentucky, Lexington, KY, 40536, USA.
Department of Behavioral Science, College of Medicine, University of Kentucky, Lexington, KY, 40536, USA.
Geroscience. 2025 Feb 5. doi: 10.1007/s11357-024-01498-1.
There is growing interest in studying vascular contributions to cognitive impairment and dementia (VCID) and developing biomarkers to identify at-risk individuals. A combination of biofluid and neuroimaging markers may better profile early stage VCID than individual measures. Here, we tested this possibility focusing on plasma levels of S100 calcium-binding protein B (S100B), which has been linked with blood-brain-barrier (BBB) integrity, and neuroimaging measures assessing BBB function (water exchange rate across the BBB (k)) and cerebral small vessel disease (white matter hyperintensities (WMHs)). A total of 74 older adults without dementia had plasma samples collected and underwent cognitive assessment. A subsample had neuroimaging data including diffusion prepared pseudo-continuous arterial spin labeling (DP-pCASL) for assessment of BBB k and T2-weighted fluid-attenuated inversion recovery (FLAIR) for quantification of WMHs. Results indicated that higher plasma S100B levels were associated with poorer episodic memory performance (β = - .031, SE = .008, p < .001). Moreover, significant interactions were observed between plasma S100B levels and parietal lobe BBB k (interaction β = .095, SE = .042, p = .028) and between plasma S100B levels and deep WMH volume (interaction β = - .025, SE = .009, p = .007) for episodic memory. Individuals with the poorest memory performance showed both high plasma S100B and either low BBB k in the parietal lobe or increased deep WMH burden. Taken together, our results provide support for the combined use of biofluid and neuroimaging markers in the study of VCID.
对研究血管因素对认知障碍和痴呆（VCID）的影响以及开发用于识别高危个体的生物标志物的兴趣与日俱增。与单独的测量方法相比，生物流体和神经影像学标志物的组合可能能更好地描绘早期VCID的特征。在此，我们聚焦于S100钙结合蛋白B（S100B）的血浆水平来测试这种可能性，S100B与血脑屏障（BBB）完整性有关，同时我们还采用了评估BBB功能（BBB的水交换率（k））和脑小血管疾病（白质高信号（WMHs））的神经影像学测量方法。共有74名无痴呆的老年人采集了血浆样本并接受了认知评估。一个子样本有神经影像学数据，包括用于评估BBB的k值的扩散准备伪连续动脉自旋标记（DP - pCASL）和用于量化WMHs的T2加权液体衰减反转恢复（FLAIR）。结果表明，较高的血浆S100B水平与较差的情景记忆表现相关（β = - 0.031，标准误 = 0.008，p < 0.001）。此外，观察到血浆S100B水平与顶叶BBB的k值之间存在显著交互作用（交互作用β = 0.095，标准误 = 0.042，p = 0.028），以及血浆S100B水平与深部WMH体积之间存在显著交互作用（交互作用β = - 0.025，标准误 = 0.009，p = 0.007）对情景记忆的影响。记忆表现最差的个体表现出高血浆S100B水平，同时伴有顶叶低BBB的k值或深部WMH负担增加。综上所述，我们的结果为在VCID研究中联合使用生物流体和神经影像学标志物提供了支持。
