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

• 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
• 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' 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

 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成像中心的助理研究教授。我的研究生和研究生工作主要集中在神经成像生物标记物上，用于检测和诊断阿尔茨海默病(AD)和其他临床前和前驱症状阶段的痴呆。我的长期职业目标是成为一名独立的研究员，专注于开发检测和诊断阿尔茨海默病等神经退行性疾病的工具。作为实现我长期职业目标的工具，同时扩展我的知识和专业知识，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，以更好地了解现有证据表明在疾病早期阶段与AD病理生理学同时发展并可能先于AD病理生理学发展的多感觉变化。测量视觉功能(使用倍频技术评估对比敏感度)、视网膜形态(通过光学相干断层扫描测量视网膜萎缩)、嗅觉识别测量(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测量(纯音测听；将在没有心理测量缺陷1或遗传背景(阿尔茨海默病家族病史和/或载脂蛋白e4等位基因携带者)的情况下，对有发展为阿尔茨海默病风险的老年人(60岁或以上)、遗忘性轻度认知障碍患者、阿尔茨海默病前驱阶段的患者以及年龄匹配、认知正常、没有主诉或已知遗传风险的健康对照组进行评估(分词句子识别、词典数字测试、带有同侧竞争信息的合成句子识别)。我将研究以下具体目标：[1]检验多种感觉模式结合将提供有关微妙认知变化的互补信息并预测老年人在AD临床前和前驱症状阶段的未来下降的假说；[2]测试AD临床前和前驱症状阶段的多感觉下降是由大脑淀粉样蛋白沉积和/或神经变性驱动的假说，以根据目前AD2的理论框架确定感觉功能障碍的阶段特异性；[3]测试该假说，即在临床前和AD前驱症状阶段中，感觉网络内的大脑连通性改变与多感觉功能的测量有关。这项研究的长期目标是更好地了解临床前和前驱AD感觉变化背后的病理生理学，以及建立新的、非侵入性的和廉价的生物标记物来检测早期AD的神经病理。经过验证后，我预计这些措施将用于临床环境中的筛查和/或诊断，通过针对最有可能进展为AD的患者进行治疗或生活方式干预来改善患者护理。经过验证的感觉生物标记物也可以用于新的AD治疗试验，以改进筛查、样本丰富，并有可能作为疗效结果衡量标准。