Blood Pressure, Microinfarcts, and Dementia: A Pathway for Alzheimer's Disease Management

项目摘要 血压、微梗塞和痴呆症：阿尔茨海默病治疗的途径 保持最佳的认知功能是成功衰老的重要组成部分之一。阿尔茨海默氏症 疾病(AD)是老年人痴呆症的主要原因，预计每年都会增加。 高血压是脑血管病变最强大的危险因素，导致痴呆。两者都有 抗高血压药物和脑血管疾病引起的高血压和血压下降 (如脑淀粉样血管病、动脉硬化)是影响微梗塞(MIF)的重要因素。 痴呆症前的形成和神经退行性改变。因此，MIF可能会在 血压与痴呆的关系。 皮质MIF与认知损害有显著的相关性。考虑到它在衰老中的重大作用 通过适当的血压监测和治疗来预防MIF的形成，对大脑结果至关重要。 由于至少5年的长期高血压是MIF形成的一个特别重要的因素， 通过丰富的数据，可以更好地了解BP曲线和脑老化结果之间的关系 老年人纵向社区数据集，如成人思维变化(ACT)尸检数据 800例。关于局部微血管的决定因素，存在着基本的知识空白 易损性和复原性及其病理过程之间潜在相互作用的机制 微血管损伤与阿尔茨海默病因此，我们将通过研究两者之间的复杂相互作用来填补空白 高血压、血管疾病、MIF和痴呆症通过以下具体目标： 1)研究老年血压(收缩压、舒张压、脉压)与局部血压的关系。 皮质(额叶、颞叶、顶叶和枕叶)和皮质下(尾状核)的特定量化MIF 核、壳核、内囊和丘脑)MIF，控制APOE基因、年龄、Braak 阶段(III-VI)和抗高血压药物的使用。 2)检查血管病变(脑淀粉样血管病、动脉硬化)之间的关系 和特定地区的MIF。 3)探讨MIF与不同性别痴呆发病风险的关系。 我们将与来自ACT(U01 AG 06781)的具有良好特征的个人小组一起开展我们的项目 由美国国家航空航天局资助的尸检队列(年龄≥65岁)(n=800)研究。这项研究将填补病理生理学方面的根本空白 血管损伤和认知障碍的机制。本研究的创新之处包括纵向的、 前瞻性收集的基于社区的研究数据；对系统性和中心性决定因素的评估 以及评估区域微血管脆弱性和复原力的决定因素及其关联 患有痴呆症。

Project Summary Blood pressure, Microinfarcts, and Dementia: A Pathway for Alzheimer’s Disease Management Maintaining optimal cognitive function is one of the important components of successful aging. Alzheimer’s disease (AD) is the leading cause of dementia in older adults and it is projected to increase every year. Hypertension is the most powerful risk factor for cerebrovascular pathology, leading to dementia. Both hypertension and decreased blood pressure (BP) from antihypertensives as well as cerebral vasculopathies (e.g., cerebral amyloid angiopathy, arteriolosclerosis) are significant factors influencing microinfarcts (MIFs) formation and neurodegenerative changes prior to dementia. Thus, MIFs might play an important role in the relationship between BP and dementia. Cortical MIFs have significant association with cognitive impairment. Considering its significant effect in aging brain outcomes, preventing the formation of MIFs through proper monitoring and treatment of BP are essential. Since long-term hypertension for at least 5 years is an especially significant contributor for the MIFs formation, the relationship between BP profile and aging brain outcomes can be better understood through a rich longitudinal community-based dataset of older adults like the Adult Changes in Thought (ACT) autopsy data (n=800). Fundamental gaps in knowledge exist with regard to the determinants of regional microvascular vulnerability and resilience and mechanisms of potential interactions between pathologic processes of microvascular injury and AD. Thus, we will fill the gaps by examining the complex interplay between hypertension, vasculopathies, MIFs, and dementia through the following specific aims: 1) To examine the relationships between late-life BP (systolic BP, diastolic BP, pulse pressure) and region- specific quantified MIFs in cortical (frontal, temporal, parietal, and occipital) and subcortical (caudate nucleus, putamen, internal capsule, and thalamus) MIFs, controlling for APOE genotype, age, BRAAK stage (III - VI), and antihypertensive medication use. 2) To examine the relationships between vasculopathies (cerebral amyloid angiopathy, arteriolosclerosis) and region-specific MIFs. 3) To examine the relationship between MIFs and the risk of dementia by sex. We will conduct our project with the well-characterized group of individuals from the ACT (U01 AG 06781) autopsy cohort (age ≥ 65) (n=800) study funded by NIA. The study will fill fundamental gaps in pathophysiologic mechanisms of vascular injury and cognitive impairment. Innovations of this study include longitudinal, prospectively collected community-based research data; assessment of systemic and central determinants of MIFs; and assessment of determinants of regional microvascular vulnerability and resilience and its association with dementia.