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

中风后正常出现的白质扩散特性和跨年龄的认知轨迹

• 批准号: 10587479
• 负责人: Carson J Ingo
• 金额: $ 72.73万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2028-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10587479
• 关键词: Acute; Age; Alzheimer' s Disease; Alzheimer' s disease related dementia; Anisotropy; Black race; Blood Vessels; Cognition; Cognitive; Contralateral; Corpus Callosum; Data; Diffusion; Diffusion Magnetic Resonance Imaging; Family; Image; Impaired cognition; Impairment; Individual; Infarction; Ischemic Stroke; Knowledge; Laboratories; Location; Measures; Modeling; Morphology; Outcome; Patients; Pattern; Prognosis; Property; Risk; Severities; Stroke; Structure; Therapeutic Intervention; Time; Tissues; White Matter Hyperintensity; Woman; acute stroke; age related; aged; brain magnetic resonance imaging; cognitive recovery; demographics; design; health disparity populations; middle age; mild cognitive impairment; neuroimaging marker; new therapeutic target; post stroke; post stroke cognitive impairment; predictive modeling; prevent; prognostic; stroke cognitive outcome; stroke outcome; stroke patient; stroke recovery; stroke risk; vascular risk factor; white matter

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.

项目概要 中风后认知障碍很常见，尤其是在老年人中，现有的知识差距。 导致不良结果的机制，尤其是老年人的不良结果，一直是最重要的障碍 开发新的治疗靶点和方法来预防认知能力下降和进展为阿尔茨海默病 疾病及相关痴呆症 (ADRD) 这与健康差异人群尤其相关。 女性和黑人人口统计数据。以前对阿尔茨海默病和轻度认知障碍的研究， 表明胼胝体的形态变化与现有数据有关。 表明经典的神经影像生物标志物，例如急性梗塞体积、位置和白质 高信号负荷在卒中后认知功能模型中具有适度的预后预测效用。 最近在急性中风患者中使用弥散张量成像表明，各向异性分数降低 同侧和对侧半球正常白质以及胼胝体的 与较高的卒中量表损伤严重程度相关。 成像检查具有显着血管危险因素的中年个体的白质微结构，以及 我们的初步结果表明，黑人和女性面临中风和认知障碍的风险。 胼胝体和其他参与认知的白质结构表现出特定的扩散 这些变化不仅与血管危险因素负担暴露有关，还与中风后的结果有关。 实验室开创了扩散 MRI 采集和建模方法，不仅对白种人敏感 物质各向异性，还有白质复杂性，因此，我们已经做好了全面表征的准备。 急性中风患者及其患者的正常白质随时间和年龄的扩散特性 我们在敏感的扩散成像和建模方面积累了丰富的专业知识。 白质复杂性与年龄相关血管风险状况的存在相关，使我们能够 纵向检查梗塞和非梗塞胼胝体的独特微观结构特性 对侧未病变半球上的组织和更远端的结构及其与术后的关系 因此，有可能更深入地了解急性期脑白质微观结构。 缺血性中风后的阶段及其随时间的变化，将增强中风后认知的预测模型 这些知识也将帮助我们的忠诚者康复并确定治疗干预的新目标。 为患者及其家属提供急需的床边预后，我们的中心假设是，之后。 单侧缺血性中风，正常白质的扩散特性随时间变化 特别是胼胝体，以及整个两个半球的白质，都与 中风后年龄相关认知轨迹的差异模式。