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.

项目概要 检测阿尔茨海默病 (AD) 和轻度认知障碍 (MCI) 前驱阶段的早期症状 AD 对于具有成本效益的临床试验、制定有针对性的干预策略和 从当前可用的治疗计划中获得最大的益处。然而，由于本质上的差异 认知障碍的表现，临床前认知变化与年龄相关的认知变化无法区分 衰退。尽管使用神经心理学、体液和成像生物标志物的组合方法相对较有效。 改善了 AD 的及时诊断，这些生物标志物的测量昂贵且技术含量高 - 依赖性，使得这些技术对于不同环境下的许多老年人来说不切实际。此外， 通过使用神经心理学电池评估认知功能仍然是临床的金标准 干预效果的试验和评估。因此，识别早期探测器至关重要：1） AD 的病理学，2）对未来认知变化的强烈预测，以及 3）跨不同的可访问性和可行性 设置。根据我们最近的研究结果，该研究发现言语运动控制措施可以作为一种强有力的帮助 索引神经退行性疾病的早期阶段，例如肌萎缩侧索硬化症和原发性进行性进展 失语症，我们建议评估言语标记作为替代或补充且生态有效 识别因 AD 导致认知障碍风险的成年人的策略。语音生成是其中之一 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结合 这些都会随着年龄的增长而改变。我们假设与年龄相关的言语变化率 成人的运动控制可能受到 AD 遗传易感性的影响。此外，我们假设 在认知要求较高的言语任务期间引发的言语测量可以区分 APOE ε4 的携带者（即 已知会增加 AD 风险的主要基因）来自非携带者以及基线语音声学和运动学测量 可以预测以后的认知能力下降。拟议的研究将创新地​​使用声学和关节运动学 结合神经影像学来追求三个目标。在目标 1 中，我们将确定衰老对言语的影响 APOE ε4 阳性 (ε4+) 和 APOE ε4 阴性 (ε4-) 基因型成人的运动控制在性别和年龄方面相匹配 教育。在目标 2 中，我们将确定与年龄相关的变化的大脑结构和静息态功能基础。 具有 ε4+ 和 ε4- 基因型的成年人的言语测量。最后，在目标 3 中，我们将确定 1) 基线语音是否 声学/运动学测量可预测两年内的认知变化，如霍普金斯学习测试所量化的- ε4+ 和 ε4- 组的修订 (HVLT-R) 和越野测试 (TMT) 分数以及 2) 如果言语和认知发生变化 通过大脑结构和功能的改变来调节。这项研究的结果将提供关键信息 关于言语运动控制的测量可以有效地纳入神经心理学测试以优化 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.