White Matter Tract Integrity Biomarkers of Neurodegeneration in Aging and MCI Administrative Supplement

衰老过程中神经退行性变的白质束完整性生物标志物和 MCI 行政补充剂

基本信息

批准号：
10087215
负责人：
Andreana Benitez
金额：
$ 5.31万
依托单位：
MEDICAL UNIVERSITY OF SOUTH CAROLINA
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-05-01 至 2021-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10087215
关键词：
Address Administrative Supplement Aging Alzheimer&apos s Disease Alzheimer’s disease biomarker Amyloid Amyloidosis Award Axon Biological Assay Biological Markers Biometry Brain Clinical Clinical Research Cognitive aging Cognitive deficits Complement Consequentialism Data Dementia Detection Diagnosis Diagnostic Diffusion Foundations Funding Goals Image Impaired cognition Institutes Investigation K-Series Research Career Programs Knowledge Language Light Longitudinal Studies Magnetic Resonance Imaging Memory Mentored Patient-Oriented Research Career Development Award Mentors Myelin Nerve Degeneration Neurobiology Neurodegenerative Disorders Neuropsychological Tests Participant Patients Plasma Positron-Emission Tomography Prevalence Provider Psychometrics Public Health Publishing Research Research Personnel Structure Testing Training Work biophysical model career cerebral amyloidosis cerebral atrophy clinical Diagnosis clinical biomarkers density effective therapy executive function experience follow-up hippocampal atrophy improved magnetic resonance imaging biomarker mild cognitive impairment multimodality neurofilament neuroimaging marker outcome forecast patient oriented pre-clinical public health priorities research clinical testing skills tau Proteins therapy development white matter

项目摘要

PROJECT SUMMARY/ABSTRACT The following section was taken directly from the awarded K23 application. The prevalence of Alzheimer's disease (AD) is projected to triple by 2050. To address this imminent public health concern, in 2011 the NIA-AA published revised diagnostic criteria for AD dementia and its anteceding stage, mild cognitive impairment (MCI). These criteria allow providers to determine the likelihood that a patient's cognitive impairment is due to AD using biomarkers of cerebral amyloidosis (e.g. via Amyloid PET) and neurodegeneration (e.g. hippocampal atrophy via structural MRI). Recent tests of these criteria indicate that MCI patients who have biomarker evidence of neurodegeneration are likely to develop dementia, irrespective of amyloidosis. Thus, given the consequential impact of neurodegeneration on dementia onset, the proposed study seeks to address the need for complementary biomarkers of neurodegeneration that can provide specific topographical and neurobiological correlates of cognitive deficits in MCI. The Applicant proposes to develop white matter tract integrity (WMTI) biomarkers of neurodegeneration derived from the biophysical modeling of diffusional kurtosis imaging (DKI) parameters. Study participants will be composed of 80 clinically diagnosed MCI patients who will undergo a clinical evaluation, neuropsychological testing, MRI, and a 2-year follow-up clinical evaluation for diagnostic confirmation. The study aims to determine the extent WMTI metrics of axonal density and myelin integrity detect neurodegeneration throughout the brain beyond hippocampal atrophy, correlate with psychometrically sophisticated tests of memory, language, and executive functions, and complement other investigational MRI biomarkers of neurodegeneration (i.e. cortical atrophy, functional connectivity). The candidate for this Mentored Patient-Oriented Career Development Award (K23), Dr. Benitez, is a clinical neuropsychologist whose career goal is to improve the diagnosis and prognosis of cognitive decline in aging and AD. The proposed K23 will extend her prior training in quantitative MRI of brain white matter compromise in cognitive aging during her institutional KL2 award. Specifically, she proposes didactic and applied training experiences to 1) become proficient in multi-modal MRI research to the level of an independent investigator, 2) acquire foundational knowledge on the neurobiology of aging/AD on which the interpretation of MRI findings is predicated, and 3) develop essential skills in the responsible conduct of clinical research in aging/AD, with the support of an outstanding mentoring team of senior researchers in MRI (Dr. Helpern), aging/AD neurobiology (Dr. Granholm), patient-oriented clinical research (Drs. Clark and Ovbiagele), and biostatistics (Dr. Nietert). By the end of the award, Dr. Benitez will have preliminary data for an R01 that will extend this project to a longitudinal study including Amyloid PET. This R01 will investigate WMTI metrics as clinical biomarkers of both neurodegeneration and amyloidosis, as recent preclinical findings suggest this may be possible with DKI but not diffusion tensor imaging. This work will address a multi-institute funding priority for biomarkers of cognitive decline across neurodegenerative diseases, for which no effective therapies exist. The requested funds for this administrative supplement will be dedicated to the efficient processing of the MRI data and to assaying collected plasma for AD biomarkers (i.e. AB40, AB42, tau, neurofilament light) to complement the proposed aims and to enhance the preliminary data for the subsequent R01.

项目摘要/摘要以下部分直接从授予的K23申请中获取。阿尔茨海默氏病（AD）的患病率预计到2050年将三倍。健康问题，2011年，NIA-AA已发布了AD痴呆及其先进的修订诊断标准阶段，轻度认知障碍（MCI）。这些标准允许提供者确定一个可能性患者的认知障碍是由于AD使用脑淀粉样变性的生物标志物（例如，通过淀粉样蛋白PET）和神经变性（例如，通过结构MRI进行海马萎缩）。这些标准的最新测试表明具有神经退行性证据的MCI患者可能会发展痴呆，不论淀粉样变性。因此，鉴于神经变性对痴呆发作的影响，拟议的研究旨在满足对可以互补的神经变性生物标志物的需求提供MCI认知缺陷的特定地形和神经生物学相关性。申请人提议开发从源自的神经变性的白质完整性（WMTI）生物标志物扩散峰度成像（DKI）参数的生物物理模型。研究参与者将由 80名临床诊断的MCI患者将接受临床评估，神经心理学测试，MRI，以及为期2年的随访临床评估，以进行诊断确认。该研究旨在确定程度轴突密度和髓磷脂完整性的WMTI指标检测整个大脑的神经变性海马萎缩，与对记忆，语言和高管的精神法法学复杂测试相关功能，并补充其他研究的神经变性的MRI生物标志物（即皮质萎缩，功能连接）。这项受过指导的以患者为导向的职业发展奖（K23）的候选人， Benitez博士是一名临床神经心理学家，其职业目标是改善诊断和预后衰老和AD的认知能力下降。提出的K23将扩大她先前在大脑定量MRI方面的培训白质在其机构KL2奖期间的认知衰老中妥协。特别是，她建议教学和应用培训经验1）熟练精通多模式MRI研究的水平独立研究者，2）获得有关衰老/AD神经生物学的基础知识 MRI发现的解释是鉴定的，3）在负责任的临床行为方面发展基本技能在衰老/广告中的研究，在MRI高级研究人员的杰出指导团队的支持下（博士 Helpern），老化/AD神经生物学（Granholm博士），以患者为导向的临床研究（Clark和Ovbiagele博士），和生物统计学（Nietert博士）。在奖项结束时，贝尼特斯博士将获得R01的初步数据将把这个项目扩展到包括淀粉样蛋白宠物在内的纵向研究。此R01将调查WMTI指标正如最近的临床前发现一样使用DKI，但不能扩散张量成像。这项工作将解决多个基金会的优先级神经退行性疾病的认知下降的生物标志物，不存在有效疗法。该行政补充的要求的资金将致力于有效处理MRI 数据并分析用于AD生物标志物的血浆（即AB40，AB42，Tau，Neurofilement Light）补充提出的目的并增强随后R01的初步数据。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Women's leadership in neuropsychology: historical perspectives, present trends, and future directions.

女性在神经心理学领域的领导地位：历史观点、当前趋势和未来方向。

DOI：
10.1080/13854046.2017.1420234
发表时间：
2018
期刊：
The Clinical neuropsychologist
影响因子：
0
作者：
Sachs,BonnieC;Benitez,Andreana;Buelow,MelissaT;Gooding,Amanda;Schaefer,LynnA;Sim,AnitaH;Tussey,ChriscelynM;Shear,PaulaK
通讯作者：
Shear,PaulaK

Validity of Normative Volumetric Estimates from Open Access Software in Amnestic Mild Cognitive Impairment.