Associative learning and brain structure in individuals at risk for dementia

有痴呆风险的个体的联想学习和大脑结构

• 批准号: 8250364
• 负责人: Catherine Brawn Fortier
• 金额: $ 15.65万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8250364
• 关键词: Address; Adult; Age; Age-associated memory impairment; Aging; Aging-Related Process; Alcoholism; Alleles; Alzheimer' s Disease; Alzheimer' s disease risk; Amnesia; Anatomy; Animals; Apolipoproteins; Area; Behavior; Behavioral; Blinking; Blood Glucose; Brain; Brain imaging; Brain region; Calculi; Cerebrovascular Disorders; Cholesterol; Classification; Clinical; Cognition; Cognition Disorders; Cognitive; Complex; Conditioned Stimulus; Cues; Dementia; Development; Diabetes Mellitus; Diagnosis; Diffusion Magnetic Resonance Imaging; Discrimination; Discrimination Learning; Disease; Dissociation; Elderly; Ensure; Environment; Epidemiology; Episodic memory; Genetic; Genetic Risk; Health Transition; Hippocampus (Brain); Histopathology; Hypertension; Image; Impairment; Individual; Instruction; Investigation; Learning; Life; Link; Magnetic Resonance Imaging; Maps; Measurable; Measures; Medial; Memory; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methodology; Nature; Neurobiology; Neurologic; Neuropsychological Tests; Neuropsychology; Patients; Pattern; Performance; Phase; Physiological; Population; Preparation; Process; Prosencephalon; Research; Research Project Grants; Research Training; Resources; Reversal Learning; Risk; Risk Factors; Stimulus; Structure; Structure-Activity Relationship; System; Techniques; Temporal Lobe; Time; Training; Variant; Vascular Dementia; age related; career; classical conditioning; cognitive change; cognitive neuroscience; conditioning; disorder risk; executive function; follow-up; frontal lobe; gray matter; hypercholesterolemia; middle age; morphometry; neuroimaging; neuropsychological; public health relevance; relating to nervous system; response; skills; stem; white matter

DESCRIPTION (provided by applicant): This application for a Mentored Patient-Oriented Research Career Development Award (K23) is intended to provide specific skills and mentorship to the candidate in complementary and integrative areas of cognitive neuroscience in preparation for an independent research career. This proposal describes a comprehensive five- year training plan focused on expanding the candidate's skills and developing expertise in the following three areas: (1) theoretical and applied aspects of the neuropsychology of aging and dementia risk, (2) structural imaging methodologies with an emphasis on diffusion tensor imaging (DTI), and (3) the integration of these two areas with an experimental learning paradigm, eyeblink classical conditioning (EBCC), to better understand the nature of brain structure-function relationships. The focus of this proposal and training plan lies in the strength of each approach and the synergy gained through their integration. This will be accomplished with advanced training, mentorship, didactics, and formal instruction in these content areas in an enriched training environment with a team of skilled and dedicated mentors, consultants, and advisors. The training environments will provide excellent institutional support and tremendous resources to the candidate. The mentors, advisors, and consultants include experts in each facet of proposed training and research areas and will ensure exemplary guidance. The proposed research project will use the eyeblink classical conditioning paradigm and neuropsychological assessment to link behavioral changes to underlying neuropathological changes in a population of aging individuals at risk for Alzheimer's disease (AD) and cerebrovascular disease (CVD). AD and CVD adversely impact the brain in different regions and are characterized by distinct neuroanatomical and neuropsychological underpinnings. These brain regions have been implicated in the circuit underlying the acquisition and expression of EBCC associative responses. This proposal has three specific aims: (1) to determine if performance in a complex EBCC learning task can dissociate individuals at risk AD from CVD, (2) to determine if these learning impairments will be associated with dissociable morphometric changes, and (3) to examine the rates of decline longitudinally. PUBLIC HEALTH RELEVANCE: Evidence suggests that cognitive disorders that are increasingly prevalent with age have their beginnings in physiological, anatomical, and cognitive alterations that are in place years before a clinical entity is detected. This project will determine if EBCC can detect behavioral changes in individuals at risk for dementia before those diseases develop, and provide unique information on brain structure-function relationships.

描述（由申请人提供）：该申请申请受到指导的以患者为导向的研究职业发展奖（K23）旨在为认知神经科学的互补和综合领域提供特定的技能和指导，以准备独立研究职业。 This proposal describes a comprehensive five- year training plan focused on expanding the candidate's skills and developing expertise in the following three areas: (1) theoretical and applied aspects of the neuropsychology of aging and dementia risk, (2) structural imaging methodologies with an emphasis on diffusion tensor imaging (DTI), and (3) the integration of these two areas with an experimental learning paradigm, eyeblink classical conditioning （EBCC），以更好地理解大脑结构功能关系的性质。该提案和培训计划的重点在于每种方法的实力以及通过整合而获得的协同作用。这将通过在丰富的培训环境中与一组熟练和敬业的导师，顾问和顾问团队在丰富的培训环境中在这些内容领域中的高级培训，指导，教学和正式教学实现。培训环境将为候选人提供出色的机构支持和巨大的资源。导师，顾问和顾问包括拟议的培训和研究领域各个方面的专家，并将确保指导典范。拟议的研究项目将使用Ekeblink经典的调理范式和神经心理学评估将行为变化与有阿尔茨海默氏病风险（AD）和脑血管疾病（CVD）风险的老年人的基本神经病理学变化联系起来。 AD和CVD在不同地区对大脑产生不利影响，其特征是不同的神经解剖学和神经心理学基础。这些大脑区域与EBCC关联反应的获取和表达的基础电路有关。该提案具有三个具体的目的：（1）确定复杂的EBCC学习任务中的表现是否可以使处于风险AD的个人与CVD相关，（2）以确定这些学习障碍是否将与可分离的形态变化相关，并且（3）以纵向研究下降的速度。 公共卫生相关性：证据表明，随着年龄的增长，越来越普遍的认知障碍在生理，解剖和认知改变方面的开始是几年来检测到临床实体之前的几年。该项目将确定EBCC是否可以检测到这些疾病发展之前处于痴呆症风险的个体的行为变化，并提供有关大脑结构 - 功能关系的独特信息。