Early Biomarkers of Alzheimer's Disease: Using Speech Markers to Detect Mild Cognitive Impairment

阿尔茨海默病的早期生物标志物：使用语音标志物检测轻度认知障碍

• 批准号: 10862942
• 负责人: Marziye Eshghi
• 金额: $ 7.56万
• 依托单位: MGH INSTITUTE OF HEALTH PROFESSIONS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10862942
• 关键词: 3-Dimensional; Acoustics; Adult; Affect; Age; Age-associated memory impairment; Aging; Alleles; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease pathology; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyotrophic Lateral Sclerosis; Anatomy; Apolipoprotein E; Biological Markers; Brain; Brain region; Clinical; Clinical Trials; Clinical assessments; Cognition; Cognitive; Cohort Studies; Complex; Data; Dementia; Detection; Diagnosis; Diagnostic; Early Diagnosis; Early Intervention; Early identification; Early treatment; Education; Elderly; Electromagnetics; Evaluation; Frequencies; Functional disorder; Future; Genes; Genetic Predisposition to Disease; Genotype; Goals; Healthcare Industry; Human; Impaired cognition; Intervention; Learning; Liquid substance; Magnetic Resonance Imaging; Measurable; Measurement; Measures; Mediating; Mentored Patient-Oriented Research Career Development Award; Motor; Movement; Neurobehavioral Manifestations; Neurodegenerative Disorders; Neuropsychological Tests; Neuropsychology; Onset of illness; Patients; Performance; Primary Progressive Aphasia; Process; Production; Research; Rest; Risk; Sampling; Sensory; Signal Transduction; Speech; Speech Acoustics; Structure; Techniques; Technology; Testing; Time; Trail Making Test; Treatment Efficacy; Uncertainty; age effect; age related; base; blood oxygen level dependent; brain tissue; clinical diagnosis; cognitive ability; cognitive change; cognitive control; cognitive function; cognitive load; cognitive process; cognitive skill; cohort; cost effective; cost efficient; detector; diagnostic strategy; disease prognosis; early detection biomarkers; functional MRI scan; imaging biomarker; improved; indexing; innovation; insight; kinematics; mechanical properties; mild cognitive impairment; motor behavior; motor control; neural correlate; neurobiological mechanism; neuroimaging; neuropathology; normal aging; physical property; pre-clinical; research clinical testing; sex; training opportunity; treatment planning

PROJECT SUMMARY Detecting early signs of Alzheimer’s disease (AD) and mild cognitive impairment (MCI) during the prodromal stage of AD is becoming increasingly important for cost-effective clinical trials, developing targeted intervention strategies, and gaining maximum benefit from currently available treatment plans. However, because of substantial differences in the manifestation of cognitive impairment, preclinical cognitive changes are not discernible from age-related cognitive decline. Although a combined approach of using neuropsychological, fluid, and imaging biomarkers has relatively improved the timely diagnosis of AD, measurement of these biomarkers is expensive and highly technology- dependent, making these techniques impractical for use in many older adults across different settings. In addition, assessment of cognitive functions through the use of neuropsychological batteries remains the gold-standard in clinical trials and evaluation of intervention efficacy. Thus, it is critical to identify early detectors that are 1) sensitive to pathologies of AD, 2) strongly predictive of future change in cognition, and 3) accessible and feasible across diverse settings. Based on our recent findings, which have identified measures of speech motor control as a powerful aid in indexing early stages of neurodegenerative diseases such as amyotrophic lateral sclerosis and primary progressive aphasia, we propose assessment of speech markers as an alternative or complementary and ecologically valid strategy for identifying adults at risk of developing cognitive impairment due to AD. Speech production is one of humans’ most complex motor behaviors, as it relies on tight integration of cognition, sensory, and motor processes which are all subject to change with advancing age. We hypothesize that the rate of age-related changes in speech motor control of adults can be influenced by genetic susceptibility to develop AD. In addition, we hypothesize that measures of speech elicited during cognitively-demanding speech tasks can differentiate carriers of APOE ε4 (i.e., the major gene known to increase AD risk) from noncarriers and that baseline speech acoustic and kinematic measures can predict later cognitive decline. The proposed research will innovatively use acoustics and articulatory kinematics in combination with neuroimaging to pursue three Aims. In Aim 1, we will determine the effect of aging on speech motor control of adults with APOE ε4 positive (ε4+) and APOE ε4 negative (ε4-) genotypes matched in sex and education. In Aim 2, we will identify the brain structural and resting-state functional bases for age-related changes in speech measures of adults with ε4+ and ε4- genotypes. Finally, in Aim 3, we will determine 1) whether baseline speech acoustic/ kinematic measures predict cognitive change over two years, as quantified by Hopkins Learning Test- Revised (HVLT-R) and Trail Making Test (TMT) scores in ε4+ and ε4- groups and 2) if speech and cognitive changes are mediated through alterations in brain structure and function. The findings of this study will provide critical information about measures of speech motor control that can be efficiently incorporated into neuropsychological testing to optimize the clinical assessment of AD.

项目摘要 检测阿尔茨海默氏病（AD）和轻度认知障碍（MCI）的早期迹象（MCI） 广告对于具有成本效益的临床试验，制定有针对性的干预策略以及 从当前可用的治疗计划中获得最大收益。但是，由于 认知障碍的表现，临床前认知变化是与年龄相关的认知无法辨别的 衰落。尽管使用神经心理学，液体和成像生物标志物的合并方法相对较 改进了AD的及时诊断，这些生物标志物的测量是昂贵且技术高度的 - 依赖，使这些技术不切实际地用于在不同环境中的许多老年人中使用。此外， 通过使用神经心理电池来评估认知功能仍然是临床的金标准 干预效率的试验和评估。这是至关重要的 AD的病理，2）强烈预测认知的未来变化，以及3）在潜水员中可访问和可行 设置。根据我们最近的发现，这些发现已将语音电机控制措施确定为有力的帮助 索引神经退行性疾病的早期阶段，例如肌萎缩性侧面硬化症和主要进行性疾病 失语症，我们建议对语音标记作为替代或完整且生态有效的评估 识别有可能因AD而产生认知障碍的成年人的策略。语音制作是 人类最复杂的运动行为，因为它依赖于认知，感觉和运动过程的紧密整合 随着年龄的增长，这都可能发生变化。我们假设与年龄相关的语音变化率 成人的运动控制可能会受到发展AD的遗传易感性的影响。此外，我们假设 在认知言语任务期间引起的语音措施可以区分Apoeε4的载体（即， 已知的主要基因会增加非载流子的AD风险）和基线语音声学和运动学测量值 可以预测后来的认知下降。拟议的研究将创新使用声学和发音运动学 结合神经影像来追求三个目标。在AIM 1中，我们将确定衰老对语音的影响 具有APOEε4阳性（ε4+）和APOEε4阴性（ε4-）基因型的成年人的运动控制 教育。在AIM 2中，我们将确定大脑结构和静止状态功能基础与年龄相关的变化 具有ε4+和ε4基因型的成年人的语音度量。最后，在AIM 3中，我们将确定1）是否基线语音 霍普金斯学习测试量化了两年来预测认知变化的声学/运动学测量值 - 如果语音和认知变化 通过改变大脑结构和功能来介导。这项研究的发现将提供关键信息 关于可以有效纳入神经心理学测试以优化的语音运动控制措施 AD的临床评估。

项目成果

Home-Based Music Therapy to Support Bulbar and Respiratory Functions of Persons with Early and Mid-Stage Amyotrophic Lateral Sclerosis-Protocol and Results from a Feasibility Study.

• DOI: 10.3390/brainsci12040494
• 发表时间: 2022-04-13
• 期刊: BRAIN SCIENCES
• 影响因子: 3.3
• 作者: Apreleva Kolomeytseva, Alisa T.;Brylev, Lev;Eshghi, Marziye;Bottaeva, Zhanna;Zhang, Jufen;Fachner, Jorg C.;Street, Alexander J.
• 通讯作者: Street, Alexander J.