Cognitive Complaints and Decline and B-Amyloid Deposition in Non-Demented Elderly

非痴呆老年人的认知障碍和衰退以及 B 淀粉样蛋白沉积

• 批准号: 8706744
• 负责人: BETH SNITZ
• 金额: $ 13.59万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8706744
• 关键词: Age; Aged, 80 and over; Aging; Alleles; Alzheimer' s Disease; Amyloid; Amyloid beta-Protein; Amyloid deposition; Autopsy; Biological Markers; Brain; Calibration; Clinic; Clinical; Cognition; Cognitive; Cognitive deficits; Data; Data Collection; Dementia; Deposition; Development; Development Plans; Educational workshop; Elderly; Elements; Emotional; Environment; Foundations; Functional Magnetic Resonance Imaging; Future; Goals; Hippocampus (Brain); Image; Impaired cognition; Individual; Lead; Learning; Magnetic Resonance Imaging; Measurement; Measures; Memory; Memory Disorders; Mental Depression; Mentors; Modeling; Moods; Natural History; Nature; Neurobiology; Neuronal Dysfunction; Neuropsychological Tests; Neuropsychology; Outcome; Parents; Participant; Pathology; Performance; Personality; Phase; Pilot Projects; Pittsburgh Compound-B; Population Study; Positron-Emission Tomography; Program Research Project Grants; Property; Psychometrics; Questionnaires; Recruitment Activity; Reporting; Research; Research Activity; Research Proposals; Risk; Role; Sampling; Scanning; Scientist; Senile Plaques; Staging; Testing; Therapeutic; Thinking; Time; Tracer; Training; Training Activity; Treatment outcome; Validation; Work; age group; base; brain metabolism; brain volume; career development; cerebral atrophy; experience; glucose metabolism; improved; mild cognitive impairment; neuroimaging; neuropathology; normal aging; novel; pre-clinical; prognostic; programs; prospective; public health relevance; response; skills; theories

DESCRIPTION (provided by applicant): Subjective declines in memory and thinking abilities are commonly reported in older adults. Recent studies indicate that complaints predict subsequent cognitive decline and incident Alzheimer's disease (AD), at least in some older adults. Furthermore, complaints have been associated with biological markers of AD, such as brain atrophy, reduced brain metabolism, and AD neuropathology on autopsy. These findings suggest that, for some, cognitive complaints likely represent a pre-symptomatic stage of AD which may provide an even earlier therapeutic opportunity than mild cognitive impairment (MCI). Amyloid-beta (A¿) imaging studies indicate that brain A¿ plaques are present in 20-30% of cognitively normal older individuals, consistent with postmortem studies. Recent reports show A¿ deposition in normal older adults to be associated with longitudinal cognitive decline, brain volume loss, and altered glucose metabolism, supporting the idea of sub-clinical neuronal dysfunction. The proposed research will investigate whether cognitive complaints may represent a facet of early A¿ -associated, sub-clinical neuronal dysfunction, along with subtle cognitive deficits and gradual cognitive decline. It will also investigate the role of personality, mood and reporting bias in the measurement of subjective cognitive complaints and their relationship to A¿ deposition. This career development proposal will provide the foundation for a research program dedicated to investigating the early natural history of cognition associated with AD pathology in aging. To date, my training has afforded me a broad background in clinical neuropsychology and functional MRI. My short-term goals are to undertake in-depth training in A¿ imaging with PET, using Pittsburgh Compound B (PiB); to learn modern psychometric approaches to develop and refine cognitive outcome scales; and to learn advanced approaches to analyzing longitudinal cognitive data. The institutional environment is well-matched to these training goals, including Mentors Dr. William Klunk, a co-inventor of the amyloid tracer PiB, and Drs. Mary Ganguli and Judith Saxton, each a leader in AD and MCI research. Key elements of the career development plan include supervised research experiences with Mentors/Consultants, courses and workshops. The research plan includes implementation of a complete, original PiB-PET study of cognitively normal participants self-referred to a Memory Disorders Clinic, as well as the step-wise development, refinement and validation of a new scale for subjective cognitive complaints. Through these training and research activities, I will establish myself as an independent scientist with a unique set of skills, utilizing neuroimaging and advances in psychometric measurement to investigate early cognitive predictors of AD. This work will contribute significantly toward understanding the prognostic significance of cognitive complaints and amyloid deposition in non-demented individuals. Potentially, it will advance understanding of the extended preclinical phase of AD and how best to initially identify it.

描述（由申请人提供）：老年人普遍报告主观记忆和思维能力下降。最近的研究表明，至少在一些老年人中，抱怨预示着随后的认知能力下降和阿尔茨海默病（AD）的发生。此外，抱怨与阿尔茨海默病的生物学标志物有关，如脑萎缩、脑代谢减少和尸检发现的阿尔茨海默病神经病理学。这些发现表明，对一些人来说，认知障碍可能代表阿尔茨海默病的症状前阶段，这可能比轻度认知障碍（MCI）提供更早的治疗机会。淀粉样蛋白（A¿）成像研究表明，20-30%认知正常的老年人中存在脑A¿斑块，与死后研究一致。最近的报告显示，正常老年人的A¿沉积与纵向认知能力下降、脑容量减少和葡萄糖代谢改变有关，这支持了亚临床神经元功能障碍的观点。拟议的研究将调查认知抱怨是否可能代表早期a¿相关的亚临床神经元功能障碍的一个方面，以及微妙的认知缺陷和逐渐的认知能力下降。它还将调查人格、情绪和报告偏差在主观认知抱怨测量中的作用及其与A¿取证的关系。这一职业发展建议将为一个研究项目提供基础，该项目致力于调查与老年痴呆症病理相关的认知的早期自然史。到目前为止，我的训练使我在临床神经心理学和功能MRI方面有了广泛的背景。我的短期目标是接受PET成像的深入培训，使用匹兹堡化合物B (PiB)；学习现代心理测量学方法，开发和完善认知结果量表；并学习分析纵向认知数据的先进方法。机构环境与这些培训目标相匹配，包括导师威廉·克伦克博士，淀粉样蛋白示踪剂PiB的共同发明者；Mary Ganguli和Judith Saxton，他们都是AD和MCI研究领域的领军人物。职业发展计划的关键要素包括导师/顾问指导下的研究经验、课程和讲习班。研究计划包括对认知正常的参与者进行完整的、原始的PiB-PET研究，这些参与者自我提到记忆障碍诊所，以及逐步开发、完善和验证一种新的主观认知抱怨量表。通过这些培训和研究活动，我将成为一名拥有独特技能的独立科学家，利用神经影像学和心理测量学的进步来研究AD的早期认知预测因素。这项工作将有助于理解认知抱怨和淀粉样蛋白沉积在非痴呆个体的预后意义。潜在地，它将促进对阿尔茨海默病延长临床前阶段的理解，以及如何最好地初步识别它。