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

血压、微梗塞和痴呆：阿尔茨海默病管理的途径

基本信息

批准号：
10477944
负责人：
Mo-Kyung Sin
金额：
$ 13.82万
依托单位：
SEATTLE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10477944
关键词：
Accounting Adult Age Aging Alzheimer&apos s Disease Alzheimer&apos s Disease Pathway Alzheimer&apos s disease related dementia American Antihypertensive Agents Attention Autopsy Blood Pressure Brain Brain region Cerebral Amyloid Angiopathy Cerebrum Cessation of life Clinical Cognition Cognitive Communities Complex Data Data Set Dementia Development Diastolic blood pressure Disease Management Elderly Fill-It Foundations Funding Genotype Health Promotion Hypertension Hypotension Impaired cognition Impairment Individual Injury Internal Capsule Knowledge Lesion Location Mediating Monitor Nerve Degeneration Neurodegenerative Disorders Neurologic Nursing Faculty Older Population Outcome Parietal Parkinson Disease Pathologic Processes Persons Pharmaceutical Preparations Play Preventive Process Prospective Studies Pulse Pressure Reporting Research Research Personnel Risk Risk Factors Role Semantic memory Severities Sex Differences Speed Stroke Syndrome Thalamic structure Therapeutic Time Vascular Dementia Vascular Diseases Visiting Nurse Visuospatial Woman Work aging brain base blood pressure control blood treatment cardiovascular health cardiovascular risk factor caudate nucleus cerebral hypoperfusion cerebral microinfarct cerebrovascular pathology cognitive function cohort community based research comorbidity dementia risk experience human old age (65+)improved innovation member personalized health care prevent programs prospective putamen resilience sex vascular injury

项目摘要

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.

项目摘要血压、微梗死和痴呆：阿尔茨海默病管理的途径保持最佳的认知功能是成功老龄化的重要组成部分之一。阿尔茨海默阿尔茨海默病（AD）是老年人痴呆症的主要原因，并且预计每年都会增加。高血压是导致痴呆的脑血管病变的最强有力的危险因素。两高血压和降压药引起的血压（BP）降低以及脑血管病 (e.g.,脑淀粉样血管病、小动脉硬化）是影响微梗死（MIFs）的重要因素形成和神经退行性变化之前，痴呆症。因此，MIFs可能在 BP与痴呆的关系皮质MIFs与认知障碍有显著相关性。考虑到它在衰老中的显著作用因此，通过适当的监测和治疗BP来预防MIFs的形成至关重要。由于至少5年的长期高血压是MIFs形成的特别重要的贡献者， BP曲线和大脑老化结果之间的关系可以通过丰富的以社区为基础的老年人纵向数据集，如成人思想变化（ACT）尸检数据（n=800）。关于局部微血管病变的决定因素，脆弱性和复原力以及微血管损伤和AD。因此，我们将通过研究以下因素之间的复杂相互作用来填补空白：高血压、血管病、MIFs和痴呆症，具体目标如下： 1)研究老年血压（收缩压、舒张压、脉压）与所在地区的关系，皮质（额叶、颞叶、顶叶和枕叶）和皮质下（尾状核）中特异性定量MIF 核、壳核、内囊和丘脑）MIFs，控制APOE基因型、年龄、BRAAK 阶段（III-VI）和抗高血压药物使用。 2)检查血管病变（脑淀粉样血管病、小动脉硬化）之间的关系和特定区域的MIF。 3)研究MIFs与性别痴呆风险之间的关系。我们将与来自ACT（U 01 AG 06781）的具有良好特征的个人小组一起开展我们的项目。尸检队列（年龄≥ 65岁）（n=800）研究，由NIA资助。这项研究将填补病理生理学的根本空白，血管损伤和认知障碍的机制。本研究的创新之处包括纵向、前瞻性收集的基于社区的研究数据;评估系统和核心决定因素， MIFs;以及评估区域微血管脆弱性和弹性的决定因素及其关联患有痴呆症