Modeling cholinergic modulation of fMRI memory networks in aging & MCI

模拟衰老过程中 fMRI 记忆网络的胆碱能调节

• 批准号: 7455849
• 负责人: ALIREZA ATRI
• 金额: $ 16.09万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-15 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7455849
• 关键词: Acetylcholine; Acetylcholinesterase Inhibitors; Affect; Age; Aging; Alzheimer' s Disease; Anatomy; Behavioral; Behavioral Model; Biological Markers; Brain; Brain region; Cholinergic Agents; Clinic; Clinical; Clinical Research; Cognition; Cognitive; Condition; Daily; Data; Detection; Development; Diagnosis; Disease; Dose; Early Diagnosis; Elderly; Equation; Event; Face; Fostering; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Hippocampal Formation; Individual; Invasive; Learning; Life; Measures; Medial; Medical; Memory; Memory impairment; Mentored Patient-Oriented Research Career Development Award; Methods; Modeling; Names; Nature; Nerve Degeneration; Neuroprotective Agents; Numbers; Paired-Associate Learning; Patients; Pattern; Performance; Pharmaceutical Preparations; Physicians; Physiology; Placebos; Process; Public Health; Research; Research Methodology; Research Personnel; Research Proposals; Scientist; Signal Detection Analysis; Standards of Weights and Measures; System; Techniques; Testing; Training; Translational Research; Visit; Work; Youth; age effect; base; behavior measurement; career; cholinergic; cognitive neuroscience; follow-up; independent component analysis; mathematical model; memory recognition; mild neurocognitive impairment; neuroimaging; normal aging; programs; relating to nervous system; response; skills; tool

This is a revised application for a K23 Mentored Patient-Oriented Research Career Development Award entitled: "Modeling Cholinergic Modulation of fMRI Memory Networks in Aging & MCI". This research proposal aims to combine functional MRI (fMRI), memory testing, medications that affect acetylcholine (ACh), and mathematical modeling to investigate the effects of aging, amnestic-mild cognitive impairment (MCI - a precursor of Alzheimer's disease, AD), and cholinergic changes on critical brain regions and their interactions during the learning of face-name pairs. Learning and remembering the names of new individuals we encounter is a particularly difficult demand in daily life and the most common memory complaint of older individuals visiting memory clinics. Meanwhile, deficits in central cholinergic function occur in the process of normal aging and become increasingly apparent in clinical AD, yet the exact nature and effects of these changes on memory systems in MCI and early AD remain elusive. Acetylcholinesterase inhibitors (AChEl) produce modest overall benefits in AD but their effects in MCI are less clear. The primary research questions in this proposal are: 1) What are the cognitive and fMRI correlates of cholinergic modulation in youth, aging and MCI? 2) Can they sensitively differentiate aging and MCI? 3) Can they serve as biomarkers to predict the 2-year clinical course of MCI? 4) Will combining pharmacological cognitive fMRI with modeling methods increase the ability to delineate the nature, functional integrity and compensatory reserve of memory systems in aging and MCI? As part of the proposed research, the candidate seeks training in: 1) fMRI analysis and modeling techniques; 2) cognitive neruoscience of aging and memory impairment; and 3) ethical clinical research methods. The proposed plan will foster the candidate's development into an independent physician-scientist using cognitive neuroscience, modeling, and pharmacological methods to study the functional neuro-anatomy, physiology, and chemisty of memory changes in aging and MCI. MCI is a condition that will affect increasing numbers of older adults and is thougth to represent a very early manifestation of AD. As more effective treatments are developed, it is an essential matter of public health to diagnose and treat AD at the earliest. This proposal works towards this goal.

这是 K23 指导的以患者为导向的研究职业发展奖的修订申请 标题为：“在衰老和 MCI 中模拟 fMRI 记忆网络的胆碱能调节”。这项研究 该提案旨在结合功能性磁共振成像（fMRI）、记忆测试、影响乙酰胆碱的药物 (ACh) 和数学模型来研究衰老、遗忘-轻度认知障碍的影响 （MCI - 阿尔茨海默氏病，AD 的前兆），以及关键大脑区域及其胆碱能的变化 学习面孔-姓名对期间的交互。 学习并记住我们遇到的新人的名字是一项特别困难的要求 日常生活和去记忆诊所的老年人最常见的记忆问题。同时， 中枢胆碱能功能的缺陷在正常衰老过程中发生，并且变得越来越严重 在临床 AD 中很明显，但这些变化的确切性质和对 MCI 和 MCI 记忆系统的影响 早期 AD 仍然难以捉摸。乙酰胆碱酯酶抑制剂 (AChEl) 对 AD 产生适度的总体益处，但 它们对 MCI 的影响尚不清楚。本提案中的主要研究问题是：1） 认知和功能磁共振成像与青年、老年和 MCI 中胆碱能调节的相关性？ 2）他们能否敏感地 区分衰老和MCI？ 3）它们可以作为预测MCI 2年临床病程的生物标志物吗？ 4）将药理学认知功能磁共振成像与建模方法相结合会增加描绘 衰老和 MCI 中记忆系统的性质、功能完整性和补偿储备？ 作为拟议研究的一部分，候选人寻求以下方面的培训：1）功能磁共振成像分析和建模技术； 2）衰老和记忆障碍的认知神经科学； 3）符合伦理的临床研究方法。这 拟议的计划将利用认知能力促进候选人发展成为一名独立的医生科学家 神经科学、建模和药理学方法来研究功能性神经解剖学、生理学、 以及衰老和 MCI 中记忆变化的化学变化。 MCI 是一种会影响越来越多老年人的疾病，被认为代表了一种非常早期的疾病 AD的表现。随着更有效的治疗方法的开发，这是公共卫生的一个重要问题 尽早诊断和治疗AD。本提案致力于实现这一目标。