Modulators of Cognitive Transifion from MCI to AD

从 MCI 到 AD 认知转变的调节器

• 批准号: 8572481
• 负责人: WILLIAM E KLUNK
• 金额: $ 33.79万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-15 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8572481
• 关键词: Accounting; Adverse effects; Affect; Age; Aging; Alzheimer' s Disease; Amyloid; Amyloid beta-Protein; Appearance; Atrophic; Autopsy; Blood Vessels; Brain; Cardiovascular system; Caregivers; Cerebrospinal Fluid; Cerebrovascular Circulation; Cerebrovascular Disorders; Cerebrum; Clinical; Cognition; Cognitive; Cohort Studies; Consent; Consultations; Data; Dementia; Deoxyglucose; Deposition; Diagnosis; Diffusion Magnetic Resonance Imaging; Dimensions; Disease; Education; Elderly; Etiology; Evaluation; Financial compensation; Future; Genotype; Ginkgo biloba; Goals; Health; Hippocampus (Brain); Homeostasis; Image; Impaired cognition; Impairment; Individual; Injury; Instruction; Laboratories; Lead; Light; Magnetic Resonance Imaging; Measurement; Measures; Mediator of activation protein; Memory; Metabolism; Methodology; Neurobehavioral Manifestations; Neurofibrillary Tangles; Neuronal Dysfunction; Neuropsychological Tests; Outcome; Outcome Study; Participant; Pathology; Patients; Perfusion; Persons; Pittsburgh Compound-B; Positron-Emission Tomography; Prevalence; Recruitment Activity; Relative (related person); Reporting; Research; Rest; Risk; Scanning; Secondary to; Spin Labels; Staging; Statistical Data Interpretation; Syndrome; Testing; Therapeutic; Time; Toxin; Variant; Vascular Diseases; Ventricular; Work; age effect; age group; amyloid imaging; apolipoprotein E-5; base; brain volume; cerebral atrophy; cerebrovascular; cognitive function; cognitive reserve; cohort; disorder subtype; in vivo; indexing; meetings; mild neurocognitive impairment; normal aging; programs; statistics; stem; tau Proteins; vascular factor

PROJECT SUMMARY (See instructions): Postmortem studies previously suggested, and in vivo amyloid imaging studies have now unambiguously confirmed that individuals with a similar burden of amyloid-beta (A|3) in their brains can be cognitively normal, have Mild Cognitive Impairment (MCI) or Alzheimer's disease (AD). Thus, it seems highly likely that there are modulators that can accelerate or retard the effects of AB on the brain. Postmortem studies also have suggested that the presence and amount of vascular pathology in the brain is a likely modulator. The overall concept is that the presence of vascular pathology in the brain establishes a vulnerable state in which the deposition of AB much more quickly leads to the onset and progression of cognitive impairment and the clinical syndromes of MCI and AD. The modulators of the transition from normal cognition to MCI will be explored in Project 4. In this project (Project 5) we will explore the modulators of the transition from MCI to clinical AD. The fundamental hypothesis is that the brain, like the rest of the body, tries to maintain homeostasis in the face of injury (induced, in this case, by AP). We propose that one of the most important mechanisms for successful homeostasis and compensation is modulation of cerebral blood flow and even subclinical cerebrovascular disease can significantly accelerate the adverse effects of AB deposition. We propose to test this hypothesis by using PiB PET to measure the effect of AB deposition (the toxin) on three main outcomes: 1) cerebral metabolism (FDG PET); 2) brain volume (structural MRI); and 3) cognition (neuropsychological testing). We also will measure potential AB modulators such as cerebral and systemic subclinical vascular disease and cerebral blood flow (perfusion MRI). We further propose that cognitive vulnerability accumulates along with markers of vascular disease with aging and in very elderly individuals, the relative importance of vascular and AB burden may be different than in younger persons. Thus, we will make use of a younger group of MCI subjects that have been studied for 24 months or more in the previous project period of this Program Project and an existing older group (>83 years) who have participated in a seven-year study of gingko biloba in aging and who have also been studied once with PiB prior to this study.

项目概要（见说明）：先前建议的尸检研究和体内淀粉样蛋白成像研究现已明确证实，具有类似β淀粉样蛋白（A| 3）在他们的大脑中可以是认知正常的，有轻度认知障碍（MCI）或阿尔茨海默病（AD）。因此，似乎极有可能存在可以加速或延缓AB对大脑影响的调节剂。尸检研究也表明，大脑中血管病变的存在和数量可能是一种调节剂。总体概念是，脑中血管病变的存在建立了一种脆弱的状态，其中AB的沉积更快地导致认知障碍的发作和进展以及MCI和AD的临床综合征。从正常认知到MCI转变的调节剂将在项目4中探索。在这个项目（项目5）中，我们将探索从MCI到临床AD转变的调节剂。基本假设是，大脑和身体的其他部分一样，在面对损伤（在这种情况下，由AP引起）时试图保持体内平衡。我们认为，成功的稳态和补偿的最重要的机制之一是脑血流的调制，甚至亚临床脑血管疾病可以显着加速AB沉积的不利影响。我们建议通过使用PiB PET测量AB沉积（毒素）对三个主要结果的影响来验证这一假设：1）脑代谢（FDG PET）; 2）脑容量（结构MRI）; 3）认知（神经心理学测试）。我们还将测量潜在的AB调节剂，例如脑和全身亚临床血管疾病和脑血流量（灌注MRI）。我们进一步提出，随着年龄的增长，认知脆弱性与血管疾病标志物一起沿着积累，在非常年老的个体中，血管和AB负担的相对重要性可能与年轻人不同。因此，我们将利用在本项目的前一个项目期间已研究24个月或更长时间的MCI受试者的年轻组，以及参与了为期7年的银杏叶衰老研究并在本研究之前使用PiB进行过一次研究的现有老年组（>83岁）。