Neural and Biochemical Mechanisms of Cognitive Aging

认知衰老的神经和生化机制

• 批准号: 8316225
• 负责人: William J. Jagust
• 金额: $ 64.83万
• 依托单位: UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-15 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8316225
• 关键词: 6-hydroxybenzothiazole; Accounting; Age; Age-associated memory impairment; Aging; Alzheimer' s Disease; Amyloid; Amyloid Proteins; Amyloid deposition; Atrophic; Attenuated; Behavioral Paradigm; Binding; Biochemical; Biological Preservation; Brain; Brain Diseases; Brain region; Characteristics; Clinical Research; Cognition; Cognitive; Cognitive aging; Data; Deposition; Disease; Elderly; Episodic memory; Event; Financial compensation; Functional Magnetic Resonance Imaging; High Prevalence; Hippocampus (Brain); Image; Individual; Laboratories; Magnetic Resonance Imaging; Measurement; Measures; Medial; Mediating; Memory; Memory Loss; Memory impairment; Methods; Modeling; Neurofibrillary Tangles; Pathology; Performance; Pittsburgh Compound-B; Play; Positron-Emission Tomography; Predisposition; Prefrontal Cortex; Process; Recruitment Activity; Rest; Role; Scientific Advances and Accomplishments; Senile Plaques; Structure; Subgroup; Techniques; Temporal Lobe; Testing; Time; age related; amyloid imaging; clinical Diagnosis; cognitive change; experience; forgetting; glucose metabolism; hippocampal atrophy; imaging modality; normal aging; novel; relating to nervous system; uptake; 6-hydroxybenzothiazole; Accounting; Age; Age-associated memory impairment; Aging; Alzheimer' s Disease; Amyloid; Amyloid Proteins; Amyloid deposition; Atrophic; Attenuated; Behavioral Paradigm; Binding; Biochemical; Biological Preservation; Brain; Brain Diseases; Brain region; Characteristics; Clinical Research; Cognition; Cognitive; Cognitive aging; Data; Deposition; Disease; Elderly; Episodic memory; Event; Financial compensation; Functional Magnetic Resonance Imaging; High Prevalence; Hippocampus (Brain); Image; Individual; Laboratories; Magnetic Resonance Imaging; Measurement; Measures; Medial; Mediating; Memory; Memory Loss; Memory impairment; Methods; Modeling; Neurofibrillary Tangles; Pathology; Performance; Pittsburgh Compound-B; Play; Positron-Emission Tomography; Predisposition; Prefrontal Cortex; Process; Recruitment Activity; Rest; Role; Scientific Advances and Accomplishments; Senile Plaques; Structure; Subgroup; Techniques; Temporal Lobe; Testing; Time; age related; amyloid imaging; clinical Diagnosis; cognitive change; experience; forgetting; glucose metabolism; hippocampal atrophy; imaging modality; normal aging; novel; relating to nervous system; uptake

PROJECT SUMMARY The cognitive aging field has long debated whether presymptomatic brain disease accounts for a proportion of what is considered to be normal age-related cognitive decline. This is most notable in relation to Alzheimer's disease (AD) not only because it is a highly prevalent age-associated condition, but also because several features of AD are seen in normal aging. In particular, decline in episodic memory, deposition of ¿- amyloid plaques, and neurofibrillary tangle-related hippocampal atrophy are all aspects of AD that are also common in cognitively intact older people. However, the effects of AD pathology are not straightforward and are likely to be mediated by intervening factors that can be characterized as vulnerability and reserve. Within the past several years, scientific advances have allowed the measurement of the multiple processes that may be involved in this model of age-related memory loss. Thus, it is possible to measure ¿-amyloid with positron emission tomography (PET) and the amyloid imaging agent [11C] Pittsburgh Compound B (PIB), to assess neurofibrillary tangle burden and hippocampal atrophy with magnetic resonance imaging (MRI), and to assess reserve processes with PET measures of glucose metabolism (using [18F]-Flurodeoxyglucose, or FDG) and with functional MRI (fMRI). In this project, a group of 125 older cognitively intact individuals will be recruited over 5 years, carefully characterized in terms of overall cognition and episodic memory, and studied with PIB- and FDG-PET imaging and structural MRI. A subgroup of 50 of these subjects, along with 50 healthy young subjects will be studied with fMRI and an event-related behavioral paradigm that contrasts brain activity during successfully remembered and forgotten items. A major question is whether, and how, older people without evidence of ¿- amyloid deposition or hippocampal atrophy differ from older people with these characteristics, and from younger people. In addition key hypotheses will be tested in continuous multivariate models in which PET measures of ¿-amyloid and MR measures of hippocampal atrophy are expected to be related to poorer episodic memory function, while resting prefrontal glucose metabolism will attenuate this relationship. Similar findings are expected during cognitive activity using fMRI, in which diminished brain activity in the medial temporal lobes may be related to ¿-amyloid deposition, and better performance may be related to increased prefrontal cortical activation. Finally, a subgroup of subjects will be re-evaluated at a 2-year interval to see whether these measures predict change over time in cognition. In total, this project will both provide a description of optimal cognitive aging independent of brain amyloid deposition, and will begin to unravel the mechanisms associated with the loss and preservation of memory function in aging.

项目摘要 认知衰老领域长期以来一直在争论，是否涉及 被认为是正常年龄相关的认知能力下降的比例。这是最值得注意的 阿尔茨海默氏病（AD）不仅是因为它是一种非常普遍的年龄相关病，而且还因为 在正常衰老中可以看到AD的几个特征。特别是，情节记忆的下降，沉积�- 淀粉样斑块和神经原纤维缠结相关的海马萎缩是AD的所有方面 在认知完整的老年人中常见。但是，AD病理的影响并不简单，并且 可能被认为是脆弱性和储备的中间因素来介导的。之内 在过去的几年中，科学进步允许测量可能的多个过程 参与与年龄相关的记忆损失模型。那就是可以用正电子测量淀粉样蛋白 排放断层扫描（PET）和淀粉样蛋白成像剂[11C]匹兹堡化合物B（PIB），以评估 具有磁共振成像（MRI）的神经原纤维缠结伯恩和海马萎缩，并评估 用葡萄糖代谢的PET测量（使用[18F] - 荧光脱氧葡萄糖或FDG）和 具有功能性MRI（fMRI）。 在这个项目中，将仔细招募一组125个老年认知完整的人 以整体认知和情节记忆为特征，并用PIB-和FDG-PET成像进行研究 和结构性MRI。这些受试者中的50个子组以及50名健康的年轻受试者将被研究 通过fMRI和事件相关的行为范式，可以在成功的过程中对比大脑活动 记住和忘记的物品。一个主要的问题是，没有证据表明的老年人以及如何 - 如何 - 淀粉样蛋白沉积或海马萎缩与具有这些特征的老年人不同，从 年轻人。另外，将在连续的多元模型中测试关键假设，其中PET 预计海马萎缩的淀粉样淀粉样蛋白和MR测量值将与较差有关 情节记忆功能，而静止的前额叶葡萄糖代谢将减弱这种关系。相似的 使用fMRI在认知活动期间有望发现结果，其中培养基中的大脑活性减少了 暂时的爱可能与 - 淀粉样蛋白沉积有关，并且表现更好可能与增加有关 前额叶皮质激活。最后，将以2年的间隔重新评估一个受试者的子组，以查看 这些措施是否可以预测认知的随着时间的变化。总的来说，这个项目都将提供 最佳认知衰老的描述独立于大脑淀粉样蛋白沉积，并将开始解开 与衰老中记忆功能的损失和保存相关的机制。