Post-stroke normal appearing white matter diffusion properties and cognitive trajectories across age

项目摘要 中风后认知障碍很常见，特别是在老年人中。现有的知识差距， 造成结果不佳的机制，特别是在老年人中，一直是最重要的障碍， 开发新的治疗靶点和方法，以预防认知能力下降和阿尔茨海默氏症的进展 疾病及相关痴呆（ADRD）。这与健康差距人群尤其相关， 女性和黑人人口统计学。先前关于阿尔茨海默病和轻度认知障碍的研究， 提示胼胝体的形态学变化与认知功能有关。现有数据 显示了经典神经成像生物标记物，例如急性梗塞体积、位置和白色物质 高强度负荷在中风后认知功能模型中具有适度预后预测效用。我们 我最近在急性中风患者中使用扩散张量成像，以显示降低的分数各向异性 同侧和对侧半球正常出现的白色物质，以及胼胝体， 与较高的卒中量表损伤严重程度相关。此外，我们还使用了高级扩散 成像检查具有显著血管危险因素的中年个体的白色物质微观结构，以及 黑人和女性有中风和认知障碍的风险。我们的初步结果表明 胼胝体和其他参与认知的白色物质结构表现出特异性扩散 这些变化不仅与血管危险因素负荷暴露有关，而且与卒中后结局有关。我们 一个实验室开创了扩散MRI采集和建模方法，不仅对白色敏感， 物质的各向异性，还有白色物质的复杂性。因此，我们准备全面描述 在急性中风患者中，正常外观的白色物质的扩散特性随时间和年龄的变化， 中风后的认知轨迹我们在扩散成像和建模方面的专业知识， 到白色物质的复杂性与年龄相关的血管风险概况的存在，使我们能够 纵向检查胼胝体，梗死和非梗死的独特的显微结构特性 组织，以及对侧非病变半球上更远的结构及其与术后的关系。 中风恢复因此，有可能更深入地了解急性脑梗死中的白色物质微结构。 缺血性卒中后的阶段及其随时间的变化，将增强卒中后认知功能的预测模型 恢复和确定治疗干预的新靶点。这些知识也将帮助我们的临床医生 为患者及其家属提供急需的床旁预后。我们的核心假设是， 单侧缺血性卒中，正常出现的脑白色物质弥散特性的时间变化， 特别是胼胝体，以及横跨两个半球的白色物质，都与大脑皮层有关。 中风后年龄相关认知轨迹的差异模式。

PROJECT SUMMARY Post-stroke cognitive impairment is common, particularly in older individuals. Existing knowledge gaps about mechanisms underpinning poor outcome, particularly in the aged, have been the most significant barriers to developing novel therapeutic targets and approaches to prevent cognitive decline and progression to Alzheimer’s disease and related dementias (ADRD). This is especially relevant to health disparity populations, specifically women and Black demographics. Previous studies of Alzheimer’s disease and mild cognitive impairment, suggest that the morphological changes of the corpus callosum are related to cognitive measures. Existing data show that classical neuroimaging biomarkers such as acute infarct volume, location, and white matter hyperintensity burden have modest prognostic predictive utility in models of post-stroke cognitive function. We have recently used diffusion tensor imaging in acute stroke patients to show that decreased fractional anisotropy of the ipsi- and contra-lateral hemispheric normal appearing white matter, as well as the corpus callosum, are associated with higher stroke scale impairment severity. Additionally, we have also used advanced diffusion imaging to examine white matter microstructure in midlife individuals with significant vascular risk factors, as well as Black and women demographics at risk for stroke and cognitive impairment. Our preliminary results suggest that the corpus callosum and other white matter structures involved in cognition manifest specific diffusion changes that not only relate to vascular risk factor burden exposure, but also to post-stroke outcome. Our laboratory has pioneered diffusion MRI acquisition and modeling approaches that are sensitive to not only white matter anisotropy, but also white matter complexity. As such, we are well poised to comprehensively characterize the diffusion properties of normal appearing white matter across time and age, in acute stroke patients and their post-stroke cognitive trajectories. Our established expertise in diffusion imaging and modeling that is sensitive to white matter complexity in relation to the presence of age-related vascular risk profiles, allows us to longitudinally examine the unique microstructural properties of the corpus callosum, infarcted and non-infarcted tissue, and more remote structures on the contralateral non-lesioned hemisphere and their relationship to post- stroke recovery. It is therefore possible that a deeper understanding of white matter microstructure in the acute stage after ischemic stroke and its change over time, will enhance prediction models of post-stroke cognitive recovery and identify novel target for therapeutic interventions. This knowledge will also help our clinicians provide much needed bed-side prognosis to patients and their families. Our central hypothesis is that after unilateral ischemic stroke, temporal changes in the diffusion properties of normal appearing white matter of the corpus callosum specifically, and the white matter across both hemispheres in general, are associated with the differential patterns of post-stroke age-related cognitive trajectories.