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: 8967290
• 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/8967290
• 关键词: Affect; Age; Alleles; Alzheimer' s Disease; Amyloid; Amyloid deposition; 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; Diagnostic; Digit structure; Disease; Early Diagnosis; Early treatment; Elderly; Family; Frequencies; Functional disorder; Future; Genetic; Genetic Risk; Goals; Hearing; Image; 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; Process; Psychometrics; Pure-Tone Audiometry; Radiology Specialty; Recording of previous events; Research; Research Personnel; Rest; Retinal; Risk; Sampling; Science; Sensory; Smell Perception; Specificity; Staging; Technology; Testing; Therapeutic; Therapeutic Intervention; Training; Universities; Validation; Vision; Work; aged; base; career; clinical Diagnosis; clinically relevant; cognitive change; cost; cost effective; disease diagnosis; experience; functional status; improved; lifestyle intervention; medical schools; mild cognitive impairment; network dysfunction; neuroimaging; neuropathology; novel; pre-clinical; prevent; professor; prophylactic; public health relevance; screening; sensory system; skills; tool; Affect; Age; Alleles; Alzheimer' s Disease; Amyloid; Amyloid deposition; 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; Diagnostic; Digit structure; Disease; Early Diagnosis; Early treatment; Elderly; Family; Frequencies; Functional disorder; Future; Genetic; Genetic Risk; Goals; Hearing; Image; 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; Process; Psychometrics; Pure-Tone Audiometry; Radiology Specialty; Recording of previous events; Research; Research Personnel; Rest; Retinal; Risk; Sampling; Science; Sensory; Smell Perception; Specificity; Staging; Technology; Testing; Therapeutic; Therapeutic Intervention; Training; Universities; Validation; Vision; Work; aged; base; career; clinical Diagnosis; clinically relevant; cognitive change; cost; cost effective; disease diagnosis; experience; functional status; improved; lifestyle intervention; medical schools; mild cognitive impairment; network dysfunction; neuroimaging; neuropathology; novel; pre-clinical; prevent; professor; prophylactic; public health relevance; 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（由适用提供）：我目前是印第安纳大学医学院放射学与成像科学系神经影像学系的助理研究教授。我的研究生和研究生工作重点是为临床前和前驱阶段的阿尔茨海默氏病（AD）和其他痴呆症的检测和诊断生物标志物进行神经影像标记。我的长期职业目标是成为一名独立研究者，重点是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大我的知识和专业知识的工具，我的短期目标是评估具有临床前和前脚AD的个体样本中多个领域中感觉功能的变化，以更好地了解可用证据的多感应变化，可用证据表明与功能相关的一致和衡量频率（通过频率衡量频率）（通过频率pofferiality pogry pofy pofy）（维持频率）（保留型号），保留型号（维持频率），保留术语学，保留术语学疗法，请保持较高的水平。嗅觉识别（宾夕法尼亚大学的气味识别测试）的测量，以及在成年人中（AGED 60或老年人）的情况下，将评估对iPsilientalitial竞争的衰落，将对成年人的缺陷评估，将对成年人的缺点评估，diichotic判决测试，合成句子识别的dichotic句子识别，二分法判决测试，合成句子识别的措施（纯粹的音调判断，二分法判决识别，合成句子识别）的测量值得缺乏症或遗传背景（家庭AD病史和/或APOE E4等位基因载体），以及具有柔滑的轻度认知障碍的患者，AD的前瞻性阶段以及年龄匹配的认知正常健康对照，而无需抱怨或已知的遗传风险。我将研究以下具体目的：[1]检验以下假设：组合多种感觉方式将提供有关微妙认知变化的完整信息，并预测AD临床前和前驱阶段的老年人未来下降； [2]检验以下假设：AD的临床前和前驱阶段的多感觉下降是由脑淀粉样蛋白沉积和/或神经变性驱动的，以确定有关AD2当前理论框架的感觉功能障碍的阶段特异性。 [3]检验了一种假设，即感觉网络中的大脑连接性改变与临床前和前驱AD中多感官功能的测量有关。这项研究的长期目标是更好地了解临床前和前驱AD的感官变化的病理生理学，并建立一种感觉测量值，例如新型，非侵入性和廉价的生物标志物，以检测早期阶段的AD神经病理学。经过验证，我希望这些措施将用于临床环境进行筛查和/或诊断，以通过针对最有可能进步的广告进行治疗或生活方式干预的广告来改善患者护理。经过验证的感觉生物标志物也可以用于新的AD处理试验中，以改善筛选，样本富集以及可能作为有效的结果指标。