The Clinical Significance of Incidental White Matter Lesions on MRI Amongst a Diverse Population with Cognitive Complaints (INDEED)

具有认知障碍的不同人群中 MRI 偶然白质病变的临床意义 (INDEED)

• 批准号: 10266149
• 负责人: Charles DeCarli
• 金额: $ 1321.22万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10266149
• 关键词: Address; African American; Aging; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer’s disease biomarker; American; Amyloid; Awareness; Biological Markers; Blood; Blood Vessels; Brain; Caring; Censuses; Characteristics; Clinical; Clinical assessments; Cognition; Cognitive; Data; Dementia; Elderly; Epidemiology; Ethnic Origin; Evolution; Future; Genetic Predisposition to Disease; Goals; Health; Hispanics; Impaired cognition; Individual; Infarction; Inflammation; Knowledge; Lesion; Life; Location; Magnetic Resonance Imaging; Measures; Mediating; Medical; Memory; Microvascular Dysfunction; Minor; Modeling; Nerve Degeneration; Outcome; PF4 Gene; Pathology; Patients; Play; Population; Population Heterogeneity; Process; Public Health; Race; Risk; Risk Factors; Role; Stroke; Therapeutic Studies; Vascular Cognitive Impairment; Vascular Diseases; Water; White Matter Hyperintensity; base; brain health; cerebrovascular; clinical phenotype; clinically significant; cognitive performance; cohort; dementia risk; effective therapy; endothelial dysfunction; executive function; inclusion criteria; inflammatory marker; injury burden; neuroimaging; non-demented; novel; novel marker; polygenic risk score; precision medicine; radiologist; risk prediction model; screening; sex; vascular risk factor; white matter; white matter injury

PROJECT SUMMARY – Overall Initially identified on MRI in 1986 as “…incidental lesions of uncertain clinical significance associated with cerebrovascular risk factors”, white matter hyperintensities (WMH) are a common consequence of the aging process exacerbated by vascular risk factors. WMH also influence cognition and evolution of WMH are associated with declines in both memory and executive function while extensive WMH predict incident MCI, stroke and dementia. WMH and infarction also have a negative impact on cognition independent or in addition to concurrent amyloid status. The impact of WMH is consistent with evidence that clinical dementia is a multifactorial processes. The impact of WMH on dementia is also consistent with the fact that dementia risk scales emphasize the role of vascular risk in dementia prediction. As the US population becomes increasingly older and more diverse, the number of Americans with dementia is expected to rise substantially, particularly for those with concomitant vascular disease. Importantly, the impact of vascular disease on dementia risk may be exacerbated in African Americans and Hispanics, who are at greater risk for vascular disease and for whom vascular disease may play a larger role in clinical dementia. As awareness of dementia increases, it is becoming common to see individuals presenting for clinical assessment with minor cognitive complaints. Neuroimaging studies frequently identify “incidental” WMH, usually ascribed to “microvascular disease” by radiologists, raising patient concerns about their brain health and future risk for dementia. To date, however, we are not aware of any studies that have comprehensively examined the impact of individual and combined MRI measures of white matter injury on cognitive performance among a diverse, non-demented, stroke free population with cognitive complaints over an extended period of observation. To address this important gap in scientific knowledge, we propose the following aims: Aim 1. To identify the extent and characteristics of white matter injury that influence cognitive and health outcomes Aim 2. Evaluate Mechanisms of progression of White Matter (WM) Injury on Cognition and Health Outcomes Aim. 3. Based on findings from Aims 1 and 2, build and validate a predictive risk model with the ultimate goal of increasing the understanding of precision medical management and planning needed by patients with white matter lesions, both for need for care as was inclusion criteria for future therapeutic studies. Impact: Given recent data showing that the impact of vascular risk factors on dementia can be modified by effective treatment in later life potentially lessening population burden of dementia, developing strategies that recognize and precisely treat the contribution of VCID to dementia burden is a public health imperative.

项目概要-总体 最初在1986年的MRI上被确定为“......与以下疾病相关的临床意义不确定的偶发性病变， 脑血管危险因素”，白色高信号（WMH）是一种常见的结果， 血管危险因素加剧的过程。WMH也影响了WMH的认知和演变， 与记忆和执行功能的下降相关，而广泛的WMH预测MCI事件， 中风和痴呆WMH和脑梗死对认知功能也有独立或附加的负面影响 并发淀粉样蛋白状态WMH的影响与临床痴呆症是一种 多因素过程WMH对痴呆症的影响也与痴呆症风险 量表强调血管风险在痴呆预测中的作用。 随着美国人口变得越来越老龄化和多样化，患有痴呆症的美国人的数量正在增加。 预计将大幅上升，特别是对于那些伴随血管疾病。重要的是，影响 在非裔美国人和西班牙裔美国人中， 血管疾病的风险更大，血管疾病可能在临床痴呆中发挥更大作用。 随着对痴呆症的认识的增加，越来越多的人出现在临床上， 轻微认知障碍的评估。神经影像学研究经常发现“偶然的”WMH， 通常被放射科医生归因于“微血管疾病”，引起了患者对大脑健康的担忧 和将来患痴呆症的风险。然而，迄今为止，我们还没有发现任何研究表明， 全面检查了白色损伤的单独和组合MRI测量的影响 在一个不同的，非痴呆的，无中风的人群中， 在长时间的观察中提出的投诉。为了填补科学知识的这一重要空白， 我们提出以下目标： 目标1。确定影响认知和健康的白色物质损伤的程度和特征 成果 目标2.评价白色物质（WM）损伤进展对认知和健康结果的机制 瞄准3.根据目标1和2的结果，建立并验证预测风险模型，最终目标是 增加对白色患者所需的精确医疗管理和规划的理解 重要病变，两者都需要护理，这是未来治疗研究的入选标准。 影响：鉴于最近的数据显示，血管危险因素对痴呆症的影响可以通过以下方式来改变： 老年痴呆症的有效治疗可能会减轻痴呆症的人口负担，制定战略， 认识和精确治疗VCID对痴呆负担的贡献是公共卫生的当务之急。