Vascular factors underlying abnormal cognitive aging

认知老化异常的血管因素

• 批准号: 8220394
• 负责人: ANGELA L. JEFFERSON
• 金额: $ 39万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-27 至 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8220394
• 关键词: Affect; Age; Aging; Alzheimer' s Disease; Appearance; Back; Blood Vessels; Brain; Cardiovascular Diseases; Cardiovascular system; Cerebrovascular Disorders; Cerebrum; Clinical; Code; Cognition; Cognitive; Cognitive aging; Collaborations; Complex; Data; Data Collection; Data Set; Databases; Dementia; Development; Diabetic Angiopathies; Diagnostic; Early identification; Elderly; Future; Gray unit of radiation dose; Health; Impaired cognition; Incidence; Individual; Infarction; International; Intervention; Investigation; Letters; Life Cycle Stages; Light; Magnetic Resonance Imaging; Measurement; Mediating; Patients; Phase; Population; Populations at Risk; Prevalence; Prevention strategy; Public Health; Research; Research Infrastructure; Research Personnel; Risk; Risk Factors; Risk Reduction; Severities; Signal Transduction; Site; Stroke; Testing; Text; Therapeutic; Time; Tissues; Vascular Diseases; Vulnerable Populations; cerebrovascular; clinical Diagnosis; cohort; disorder risk; effective therapy; follow-up; gray matter; high risk; indexing; insight; mild neurocognitive impairment; neuroimaging; neuropsychological; novel strategies; pre-clinical; prevent; prognostic; prospective; vascular factor; white matter; white matter change

DESCRIPTION (provided by applicant): As the population ages, cognitive decline and Alzheimer's disease (AD) are becoming increasingly important public health issues. Mild cognitive impairment (MCI) is considered a precursor to AD, and early identification of MCI and effective management of risk factors associated with conversion from MCI to dementia is an important step in managing the public health crisis of AD. Unfortunately, MCI is an unstable diagnostic construct, and key predictors of conversion and reversion are poorly understood. Multiple vascular factors and prevalent cardiovascular disease are known risks for the development of AD, so a plausible predictor of diagnostic fluctuations in MCI is the presence of concomitant micro vascular disease in the brain. This proposal will leverage the existing and robust dataset from the Alzheimer's Disease Neuroimaging Initiative to examine neuroimaging markers of micro vascular and microstructural tissue changes in the white matter with cognitive trajectory among cognitively normal older adults and individuals with MCI. We will (1) assess how stable versus progressive cerebral micro vascular disease and micro structural changes in white matter affect maladaptive cognitive aging over time and (2) assess the mediating effect of baseline systemic vascular disease (using a vascular health index) in the longitudinal relation between micro vascular and micro structural white matter changes and diagnostic conversion and cognitive trajectory. Insights regarding complex relations between systemic vascular disease and micro vascular or microstructural changes in the brain have important public health implications because they will contribute to early identification of a vulnerable population at high risk for cognitive progression. Furthermore, because vascular risk factors can be modified over the life course to reduce the burden of cerebrovascular disease in older adults, this vulnerable population would benefit most from novel strategies to delay or prevent progression, which is particularly valuable in light of the aging of the population and increasing prevalence of AD. PUBLIC HEALTH RELEVANCE: The incidence of dementia is dramatically increasing, and in the absence of effective therapies, there is an urgent need to identify vascular risk factors and prevention strategies. The proposed project will provide insights regarding complex relations between systemic vascular disease, micro vascular and micro structural changes on brain MRI, and early identification of a vulnerable population at risk for cognitive progression to aid in early identification and risk reduction strategies.

描述（由申请人提供）：随着人口的年龄，认知能力下降和阿尔茨海默氏病（AD）正在变得越来越重要的公共卫生问题。轻度认知障碍（MCI）被认为是AD的先驱，对MCI的早期识别以及与MCI转化为痴呆症相关的风险因素的有效管理是管理AD公共卫生危机的重要一步。不幸的是，MCI是一种不稳定的诊断构建体，对转换和回归的关键预测指标知之甚少。多种血管因素和普遍的心血管疾病是AD发展的已知风险，因此MCI诊断波动的合理预测指标是大脑中伴有微血管疾病的存在。该建议将利用阿尔茨海默氏病神经影像倡议的现有和鲁棒数据集，以检查白质中微血管和微观结构组织变化的神经影像学标记，并具有认知轨迹的认知正常成年人和具有MCI的个人的认知轨迹。我们将（1）评估白质的稳定与渐进性脑微血管疾病和微型结构变化如何随着时间的推移影响适应性的认知衰老，（2）评估基线系统性血管疾病（使用血管健康指数）在微血管和微型结构质量和微型结构白质和诊断之间的纵向关系和诊断的纵向变化。关于全身血管疾病与大脑微观或微观结构变化之间复杂关系的见解具有重要的公共卫生影响，因为它们将有助于早期鉴定出高风险的认知进展风险的脆弱人群。此外，由于可以在生命过程中修改血管危险因素，以减轻老年人的脑血管疾病负担，因此该脆弱人群将受益于延迟或预防进展的新型策略最大，这对于人群的衰老和AD患病率的增长特别有价值。 公共卫生相关性：痴呆症的发病率急剧增加，在没有有效疗法的情况下，迫切需要确定血管危险因素和预防策略。拟议的项目将提供有关全身血管疾病，微血管和微型结构变化之间的复杂关系的见解，以及对认知进展的脆弱人群的早期鉴定，以帮助早期识别和降低风险策略。