Longitudinal Risk Factor Changes and Early Recognition of Cerebral Small Vessel Disease

脑部小血管疾病(CSVD)与阿尔茨海默病(AD)、相关痴呆密切相关 (ADRD)、中风和血管认知障碍，1在30%-50%的AD患者中是严重的，2 约30%的痴呆症病例。3 CSVD仍处于亚临床阶段数年至数十年，很容易 使用临床脑MRI进行评估。CSVD最常见的后果是长期接触可修改的 风险因素，但这些风险因素以及健康行为在个人内部和个人之间随着时间的推移而变化 终生患病，并通过治疗进一步改变。这些与CSVD负担的变化关系仍然是充分的 阐明，这对于了解血管危险因素暴露的持续时间是至关重要的，这可能导致 不可逆转的脑损伤，应迅速评估CSVD的负担，以加强预防工作。vbl.使用 功能性数据分析的新应用我们将利用所获取的具有丰富特征的长期数据 在弗雷明翰心脏前瞻性研究中进行了长达70年的随访，并提供了现成的传统 MRI(可用于临床实践)与暴露于血管危险因素的趋势和持续时间相关，美国 心脏协会(AHA)生命的基本8项和预防治疗用于CSVD总分(T-CSVD) 全面评估CSVD在个体中的表现。我们将进一步研究它的作用。 T-CSVD评分在预测痴呆和卒中中的作用 措施(隐匿性脑梗塞、脑白质高信号、脑微出血、皮质浅表铁质沉着症 和扩大的血管周围间隙)，并与结合了敏感的白色测量的新分数形成对比 基于扩散张量成像的物质损伤和基于淀粉样蛋白和Tau PET的分子成像 在参与者的子集中提供的衡量标准。 我们探索性应用的成功将为全脑小血管疾病提供一个实用的评估 与突发中风和痴呆症有关，使用临床护理中可用的和急需的CSVD测量方法 洞察：i)临床实践中应考虑评估CSVD负担的年龄，和/或ii) 应导致考虑CSVD负担评估的风险因素暴露的持续时间。如果我们的 应用成功，可能改变临床实践，促进亚临床CSVD负担评估 早期实施预防性治疗的阶段。

Cerebral small vessel disease (CSVD) is strongly related to Alzheimer’s disease (AD), related dementias (ADRD), stroke, and vascular cognitive impairment,1 is severe in 30–50% of patients with AD,2 and contributes to about 30% of all dementia cases.3 CSVD remains in subclinical stages for years to decades and can be readily assessed using clinical brain MRI. CSVD is most frequently the consequence of long-term exposure to modifiable risk factors, but such risk factors as well as healthy behaviors change within and between individuals over a lifetime and are further altered by treatments. These changing relations with CSVD burden remain to be fully elucidated, which is critical to understand the duration of vascular risk factor exposure that could lead to irreversible brain injury and should prompt assessment of CSVD burden to enhance preventive efforts. Using novel applications of functional data analysis we will leverage the richly characterized long-term data acquired over up to 7 decades of follow-up in the prospective Framingham Heart Study, and readily available traditional MRI (available in clinical practice) to relate trends and duration of exposure to vascular risk factors, American Heart Association (AHA) life’s essential 8 and preventive treatment use to a total CSVD score (T-CSVD) that provides a comprehensive assessment of CSVD manifestations in individuals. We will further study the role of T-CSVD scores for prediction of dementia and stroke using traditional assessments of individual CSVD measures (covert brain infarcts, white matter hyperintensities, cerebral microbleeds, cortical superficial siderosis and enlarged perivascular spaces), and contrast with novel scores incorporating sensitive measures of white matter injury based on diffusion tensor imaging, and molecular imaging based on amyloid and Tau PET measures available in a subset of participants. Success of our exploratory application will provide a practical assessment of total cerebral small vessel disease in relation to incident stroke and dementia, using CSVD measures available in clinical care, and much needed insight into: i) the age at which assessment of CSVD burden should be considered in clinical practice, and/or ii) the duration of exposure to risk factors that should lead to consideration of CSVD burden assessment. If our application is successful, it may change clinical practice to promote assessment of CSVD burden in subclinical stages for early implementation of preventive treatments.