CLINICAL PLAQUE AND TANGLE IMAGING IN AGING AND DEMENTIA

衰老和痴呆症的临床斑块和缠结成像

• 批准号: 6949819
• 负责人: GARY William SMALL
• 金额: $ 6.46万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6949819
• 关键词: Alzheimer' s disease; aging; behavior test; bioimaging /biomedical imaging; brain imaging /visualization /scanning; cognition disorders; dementia; deoxyglucose; genetic susceptibility; human middle age (35-64); human old age (65+); human subject; longitudinal human study; magnetic resonance imaging; molecular probes; neural degeneration; neuritic plaques; neurofibrillary tangles; neuropsychological tests; neuropsychology; pathologic process; patient oriented research; positron emission tomography; protein quantitation /detection; receptor expression; serotonin receptor; small molecule

Prior research indicates that evidence of brain aging (amyloid senile plaque [SP] and neurofibrillary tangle [NFT] accumulation, neuroreceptor decline) occurs decades before individuals reach the age at risk for dementia. Moreover, current methods for detecting pre-symptomatic dementia and differentiating types of dementia are imprecise. To address these issues, this project will clarify patterns of SP and NFT brain accumulation in cognitively intact individuals (ages 30 to 80 years), individuals with MCI, and patients with mild AD and frontotemporal dementia (FTD), using 2-(1-{6-[(2-[F-18]Fluoroethyl)(methyl)amino]-2- naphthyl}ethylidene)malononitrile ([18FJFDDNP-PET) scan imaging. Cerebral patterns of SP and NFT will be determined along with informative clinical, neuropsychological, and genetic risk measures, as well as measures of regional cerebral glucose metabolism, using flurodeoxyglucose ([18F]FDG)-PET. To further clarify patterns of neurodegeneration in subjects with AD, MCI, and older controls, serotonin receptor density will be determined, using [18F]MPPF-PET. At baseline, all subjects will receive [18F]FDDNP-PET, [18F]FDG-PET, and structural MRI (in order to co-register PET data for imaging analysis) scanning, as well as genetic risk testing (e.g., APOE, H1/H1 haplotype), and clinical, behavioral, and neuropsychological assessments. Older subjects also will receive [18F]MPPF scans to measure levels of 5-HT1A receptors. Cognitively intact middle-age and older subjects, individuals with MCI, and patients with AD will be followed longitudinally, and after two years, imaging, clinical, and neuropsychological assessments will be repeated. The aims of this project are to: (1) Determine how SP and NFT brain accumulation patterns differ according to age, dementia diagnosis, and genetic risk, and how these measures correlate with patterns of neuronal deterioration; (2) Measure 5-HT1A receptor levels throughout the brain, particularly in the medial temporal lobe, and compare these signals to [18F]FDDNP measures of plaque and tangle burden, as well as regional glucose metabolic rates; and (3) Determine whether [18F]FDDNP-PET patterns and/or [18F]MPPF-PET patterns predict future cognitive and metabolic decline, and SP and NFT accumulation in the brain. This project will lead to more effective diagnosis and differential diagnosis of dementia and age-related memory loss and will provide the groundwork for reliable methods of testing interventions designed to delay the onset of dementia and treat it once it develops.

先前的研究表明，脑衰老的证据（淀粉样蛋白老年斑块[SP]和神经原纤维缠结[NFT]积累，神经感受器的下降）发生在个人达到处于痴呆症风险的人年龄之前数十年。此外，目前用于检测症状前痴呆和痴呆症分化类型的方法是不精确的。为了解决这些问题，该项目将使用2-（1- {（1- {（2-- [2-- [F-18] fluorooroethyl）（甲基） - 2-- [（2- [f-18] fluororoethyl）（甲基） - 2-- [（甲基） - 2--2-- [6- [（2- [F-18]），该项目将在认知完整个体中（30至80岁），患有MCI和轻度AD和额额叶痴呆症患者的患者以及患有轻度AD和额额叶痴呆症的患者的SP和NFT脑积累模式澄清模式。 乙酰基}乙基）马诺硝那腈（[18FJFDDNP-PET）扫描成像。使用FluroDeoxyoxyglucose（[18F] FDG）-PET，将确定SP和NFT的脑模式以及信息丰富的临床，神经心理学和遗传风险度量以及局部脑葡萄糖代谢的测量。为了进一步阐明AD，MCI和旧对照受试者中神经退行性的模式，使用[18F] MPPF-PET确定5-羟色胺受体密度。在基线时，所有受试者将接受[18F] FDDNP-PET，[18F] FDG-PET和结构MRI（为了共同注册PET进行成像分析）扫描，以及遗传风险测试（例如APOE，H1/H1/H1单倍型）以及临床，行为，行为，行为和神经心理学评估。较老的受试者还将接受[18F] MPPF扫描以测量5-HT1A受体的水平。认知完整的中年龄和较旧的受试者，患有MCI的个体以及患有AD的患者将纵向遵循，两年后，将重复成像，临床和神经心理学评估。该项目的目的是：（1）确定SP和NFT脑积累模式根据年龄，痴呆症诊断和遗传风险的不同，以及这些测量与神经元恶化模式的相关性； （2）测量整个大脑的5-HT1A受体水平，特别是在内侧 颞叶，并将这些信号与[18F] FDDNP牙菌斑和缠结负担的测量值以及区域葡萄糖代谢率进行比较； （3）确定[18F] FDDNP-PET模式和/或[18F] MPPF-PET模式是否可以预测未来的认知和代谢下降，以及大脑中的SP和NFT积累。该项目将导致对痴呆症和与年龄相关的记忆丧失的更有效的诊断和差异诊断，并为可靠的测试干预措施提供基础，旨在延迟痴呆症的发作并治疗痴呆症。