Sensory and Perceptual Measures as Biomarkers of Alzheimer's Disease Pathology

感觉和知觉测量作为阿尔茨海默病病理学的生物标志物

基本信息

批准号：
9477439
负责人：
SHANNON L RISACHER
金额：
$ 12.23万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
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：
2015-08-15 至 2020-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9477439
关键词：
Affect Age Alleles Alzheimer&apos s Disease Amyloid Amyloid deposition Anatomy Atrophic Auditory Biological Biological Markers Brain Brain Pathology Cerebrum Clinical Clinical Research Clinical Treatment Clinical Trials Cognition Cognitive Contrast Sensitivity Data Dementia Detection Deterioration Development Diagnosis Diagnosis Clinical Trials Digit structure Disease Early Diagnosis Early Intervention Early treatment Elderly Family Frequencies Functional disorder Future Genetic Genetic Risk Goals Hearing Impaired cognition Impairment Indiana Individual Ipsilateral Knowledge Lead Measures Memory Mentored Research Scientist Development Award Methodology Methods Modality Morphology Nature Nerve Degeneration Neurodegenerative Disorders Neurons Optical Coherence Tomography Outcome Measure Pathology Patient Care Patients Pennsylvania Perception Psychometrics Pure-Tone Audiometry Recording of previous events Research Research Assistant Research Personnel Rest Retinal Risk Sampling Science Sensory Smell Perception Specificity Technology Testing Therapeutic Therapeutic Intervention Training Universities Validation Vision Work aged amnestic mild cognitive impairment apolipoprotein E-4 auditory processing career clinical Diagnosis clinically relevant cognitive change cost cost effective diagnostic biomarker disease diagnosis experience functional status improved lifestyle intervention medical schools multimodality multisensory network dysfunction neuroimaging neuroimaging marker neuropathology novel pre-clinical prevent professor prophylactic public health relevance radiological imaging screening sensory system skills tool

项目摘要

DESCRIPTION (provided by applicant): I am currently an Assistant Research Professor at the Center for Neuroimaging in the Department of Radiology and Imaging Sciences at the Indiana University School of Medicine. My graduate and post-graduate work has focused on neuroimaging biomarkers for detection and diagnosis of Alzheimer's disease (AD) and other dementias in preclinical and prodromal stages. My long-term career goal is to become an independent investigator with a focus on developing tools for detection and diagnosis of neurodegenerative diseases such as AD. As a vehicle toward achieving my long-term career goals while expanding my knowledge and expertise, my short-term goal is to assess changes in sensory function in multiple domains in a sample of individuals with preclinical and prodromal AD to better understand the poly-sensory changes that available evidence suggests develop concurrent with and possibly precede AD pathophysiology in early stages of disease. Measures of visual function (contrast sensitivity assessed using frequency doubling technology), retinal morphology (retinal atrophy measured by optical coherence tomography), a measure of olfactory identification (University of Pennsylvania Smell Identification Test), and measures of tonal hearing and central auditory processing (pure tone audiometry; Dichotic Sentence Identification, Dichotic Digits Test, Synthetic Sentence Identification with Ipsilateral Competing Message) , will be evaluated in older adults (aged 60 or older) at risk for progression to AD due to the presence of subjective cognitive decline in the absence of psychometric deficits1 or genetic background (family AD history and/or APOE e4 allele carrier), as well as patients with amnestic mild cognitive impairment, a prodromal stage of AD, and age-matched cognitively normal healthy controls without complaints or known genetic risk. I will investigate the following specific aims: [1] test the hypothesis that combining multiple sensory modalities will provide complementary information about subtle cognitive change and predict future decline in older adults in preclinical and prodromal stages of AD; [2] test the hypothesis that multi- sensory decline in preclinical and prodromal stages of AD is driven by cerebral amyloid deposition and/or neurodegeneration to determine the stage-specificity of sensory dysfunction with regard to the current theoretical framework of AD2; [3] test the hypothesis that altered brain connectivity within sensory networks is associated with measures of multi-sensory function in preclinical and prodromal AD. The long-term goal of this research is to better understand the pathophysiology underlying sensory changes in preclinical and prodromal AD, as well as to establish sensory measures as novel, non-invasive, and inexpensive biomarkers for detecting AD neuropathology in early stages. After validation, I expect these measures will be used in clinical settings for screening and/or diagnosis to improve patient care by targeting those most likely to progress to AD for therapeutic or lifestyle intervention. Validated sensory biomarkers could also be used in trials of new AD treatments to improve screening, sample enrichment, and potentially as efficacy outcome measures.

描述（由申请人提供）：我目前是印第安纳大学医学院放射学和影像科学系神经影像中心的助理研究教授，我的研究生和研究生工作重点是用于检测和成像的神经影像生物标志物。我的长期职业目标是成为一名独立研究者，专注于开发用于检测和诊断 AD 等神经退行性疾病的工具。作为实现我的长期职业目标同时扩展我的知识和专业知识的工具，我的短期目标是评估临床前和前驱 AD 患者样本中多个领域感觉功能的变化，以更好地了解多感觉功能现有证据表明，在疾病早期阶段，与 AD 病理生理学同时发生或可能先于这些变化进行视觉功能测量（使用倍频技术评估对比敏感度）、视网膜形态（通过光学相干性测量视网膜萎缩）。断层扫描），嗅觉识别的测量（宾夕法尼亚大学气味识别测试），以及音调听力和中枢听觉处理的测量（纯音测听；双分句子识别，双分数字测试，同侧竞争信息的合成句子识别），将被在缺乏心理测量的情况下，由于主观认知能力下降而有进展为 AD 风险的老年人（60 岁或以上）进行了评估缺陷1或遗传背景（AD家族史和/或APOE e4等位基因携带者），以及遗忘性轻度认知障碍、AD前驱阶段的患者，以及年龄匹配的认知正常健康对照，无主诉或已知遗传风险。研究以下具体目标：[1] 检验以下假设：结合多种感觉方式将提供有关微妙认知变化的补充信息，并预测老年人在 AD 临床前和前驱阶段的未来衰退[2] 检验多感觉方式的假设； AD 临床前和前驱阶段的下降是由脑淀粉样蛋白沉积和/或神经变性驱动的，以确定相对于 AD2 当前理论框架的感觉功能障碍的阶段特异性；[3] 检验感觉网络内的大脑连接性的假设与临床前和前驱 AD 中的多感觉功能测量相关本研究的长期目标是更好地了解临床前和前驱 AD 中感觉变化的病理生理学，以及建立感觉测量作为新型、非侵入性且廉价的生物标志物，用于在早期阶段检测 AD 神经病理学。经过验证，我预计这些测量将用于临床环境中的筛查和/或诊断，通过针对最有可能的患者来改善患者护理。经验证的感觉生物标志物也可用于新的 AD 治疗试验，以改善筛查、样本富集，并可能作为疗效结果衡量标准。