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: 7147141
• 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/7147141
• 关键词: Alzheimer' s disease; anticholinergic agent; behavioral /social science research tag; bioimaging /biomedical imaging; brain disorder diagnosis; brain mapping; cholinesterase inhibitors; clinical research; cognition disorders; computational neuroscience; early diagnosis; functional magnetic resonance imaging; human middle age (35-64); human old age (65+); human subject; learning; mathematical model; memory disorders; neural information processing; neurochemistry; neuropharmacology; patient oriented research; psychological aspect of aging; scopolamine; young adult human (21-34)

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 题为：“对老化和MCI中fMRI内存网络的胆碱能调节建模”。这项研究 建议旨在结合功能性MRI（fMRI），记忆测试，影响乙酰胆碱的药物 （ACH）和数学建模，以研究衰老，动静的认知障碍的影响 （MCI-阿尔茨海默氏病，AD的前体）以及关键大脑区域及其胆碱能的变化 在学习面名对的过程中的互动。 学习和记住我们遇到的新个人的名字是一个特别困难的需求 日常生活和最常见的记忆投诉，年龄较大的人参观记忆诊所。同时， 中央胆碱能功能的缺陷发生在正常衰老的过程中，并变得越来越多 在临床广告中显而易见，但是这些变化对MCI和MCI和 早期广告仍然难以捉摸。乙酰胆碱酯酶抑制剂（ACHEL）在AD中产生适度的总体好处，但 它们在MCI中的影响不太清楚。该提案中的主要研究问题是：1） 年轻人，衰老和MCI的胆碱能调节的认知和功能磁共振成像相关性？ 2）他们可以敏感吗 区分衰老和MCI？ 3）他们可以用作生物标志物来预测MCI的两年临床课程吗？ 4）将将药理学认知功能磁共振成像与建模方法相结合，提高了描述的能力 衰老和MCI中记忆系统的自然，功能完整性和补偿储备？ 作为拟议研究的一部分，候选人寻求培训：1）fMRI分析和建模技术； 2）认知衰老和记忆力障碍的认知性障碍； 3）道德临床研究方法。这 拟议的计划将使用认知将候选人的发展促进候选人的发展成独立的医师科学家 神经科学，建模和药理方法研究功能性神经解剖学，生理学， 以及衰老和MCI的记忆变化的化学作用。 MCI是一种会影响越来越多的老年人数量的疾病，并且很早就代表一个 广告的表现。随着开发更有效的治疗，这是公共卫生的重要问题 最早诊断和治疗广告。该建议朝着这一目标实现。