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: 8516930
• 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 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8516930
• 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. PUBLIC HEALTH RELEVANCE: This research proposal will determine whether subjective complaints of impaired memory and thinking in older adults are related to the pathological brain changes of Alzheimer's disease (AD). It will investigate the role of personality, mood and reporting bias in the measurement of subjective complaints and their relationship to amyloid-beta plaques in the brain. The results could lead to the development of a new scale to initially screen for the presence of very early AD brain changes, potentially leading to improved future treatment outcomes.

描述(由申请人提供)：记忆力和思维能力的主观下降在老年人中很常见。最近的研究表明，至少在一些老年人中，主诉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，主诉与AD的生物标志物有关，如脑萎缩、脑代谢减少，以及尸检中的AD神经病理。这些发现表明，对于一些人来说，认知主诉可能代表了AD的症状前阶段，这可能提供了比轻度认知障碍(MCI)更早的治疗机会。淀粉样β蛋白(A？)成像研究表明，认知正常的老年人中有20-30%存在大脑A？斑块，这与尸检结果一致。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、脑容量减少和糖代谢改变有关，支持亚临床神经元功能障碍的观点。这项拟议的研究将调查认知主诉是否可能代表早期A？相关的亚临床神经元功能障碍的一个方面，以及轻微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投诉测量中的作用及其与A？证词的关系。这项职业发展计划将为一项研究计划提供基础，该计划致力于调查与衰老的AD病理相关的早期自然认知史。到目前为止，我的培训使我在临床神经心理学和功能磁共振方面有了广泛的背景。我的短期目标是使用匹兹堡化合物B(PIB)，在正电子发射计算机断层扫描(PET)中进行A？成像方面的深入培训；学习现代心理测量学方法，以开发和完善认知结果量表；学习分析纵向认知数据的高级方法。机构环境与这些培训目标很好地匹配，包括导师威廉·克伦克博士，淀粉样示踪剂PIB的共同发明者，以及玛丽·甘古利博士和朱迪思·萨克斯顿博士，他们都是AD和MCI研究的领导者。职业发展计划的主要内容包括指导导师/顾问的研究经验、课程和讲习班。研究计划包括对自称为记忆障碍诊所的认知正常参与者实施一项完整的原创PIB-PET研究，以及逐步开发、完善和验证主观认知投诉的新量表。通过这些培训和研究活动，我将确立自己作为一名拥有一套独特技能的独立科学家的地位，利用神经成像和心理测量的进步来研究AD的早期认知预测因素。这项工作将有助于理解认知主诉和淀粉样蛋白沉积在非痴呆患者中的预后意义。潜在地，它将促进对AD延长的临床前阶段以及如何最好地初步识别它的理解。 公共卫生相关性：这项研究提案将确定老年人记忆和思维受损的主观主诉是否与阿尔茨海默病(AD)的病理性脑变化有关。它将调查个性、情绪和报告偏见在主观抱怨测量中的作用，以及它们与大脑中淀粉样β蛋白斑块的关系。这一结果可能导致开发一种新的量表，以初步筛选AD早期大脑变化的存在，可能导致改善未来的治疗结果。