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

脑小血管病（CSVD）与阿尔茨海默病（AD）、相关性痴呆 （ADRD）、卒中和血管性认知障碍，1在30-50%的AD患者中为重度，2并且有助于 约占所有痴呆症病例的30%。3 CSVD在数年至数十年内仍处于亚临床阶段，并且很容易被治疗 使用临床脑MRI进行评估。CSVD最常见的后果是长期暴露于可改变的 风险因素，但这些风险因素以及健康行为在个体内部和个体之间发生变化， 寿命，并通过治疗进一步改变。这些变化与CSVD负担的关系仍有待充分研究。 阐明了这一点，这对于了解可能导致 不可逆的脑损伤，应及时评估CSVD负担，以加强预防工作。使用 功能数据分析的新应用，我们将利用获得的具有丰富特征的长期数据 在前瞻性心脏病研究中长达70年的随访中， MRI（临床实践中可用）与血管风险因素暴露的趋势和持续时间相关，美国 心脏协会（AHA）生命基本8和预防性治疗使用的总CSVD评分（T-CSVD）， 提供了一个全面的评估CSVD的表现在个人。我们会进一步研究 使用传统的个体CSVD评估方法预测痴呆和卒中的T-CSVD评分 测量（隐性脑梗死、白色高信号、脑微出血、皮质浅表铁质沉着 和血管周围间隙扩大），并与包含白色敏感指标的新评分进行对比 基于扩散张量成像的物质损伤，以及基于淀粉样蛋白和Tau PET的分子成像 在参与者的子集中可用的措施。 我们探索性应用的成功将为全脑小血管疾病提供实用的评估 与中风和痴呆的发病率有关，使用临床护理中可用的CSVD措施， 深入了解：i）在临床实践中应考虑CSVD负荷评估的年龄，和/或ii） 应考虑CSVD负荷评估的风险因素暴露持续时间。如果我们的 应用是成功的，它可能会改变临床实践，以促进亚临床CSVD负担的评估 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.