Digital Biomarkers for Alzheimer’s Disease

阿尔茨海默病(AD)的特点是几十年前就开始进行性的神经病变 认知和功能症状，因此一直致力于开发创新工具 以及用于早期识别痴呆前期阶段的生物标记物。到目前为止，临床上能够识别那些患有 阿尔茨海默病的痴呆前期阶段有限，需要昂贵的(淀粉样蛋白PET)或侵入性(腰椎 穿孔)测试。然而，联网语音的细微变化可能在公开之前几年就可以检测到 出现疾病症状。我们的团队开发了一种使用机器学习和自然语言的方法 语言处理与先进的声学、语音和词汇语义分析相结合。 初步数据显示，在识别AD生物标记物状态和预测2年认知能力方面有希望 进步。在拟议的研究中，我们利用我们在收集脑脊液(CSF)方面的成功 生物标记物，神经成像和详细的认知表型结合音频记录 大脑压力、高血压和老龄化研究计划的参与者。这群人，现在在它的 第三年的随访，包括400名50岁或以上、认知正常或轻度的个体 认知障碍。我们计划将这个400名参与者的队列再延长3年，以收集 其他波的语音记录，认知评估，后续脑脊液生物标志物和 神经成像。我们的主要假设是，派生的新奇特征反映了糟糕的词汇- 在生物标志物阳性之间，语义连接性或声学扰动显著不同 与阴性参与者相比，他们在ATN框架方面的诊断性能更好 传统的认知测试可以跟踪疾病的进展。具体目标是：1)确定 衍生数字生物标记物在检测B-AD患者体内AD病理和ATN分类中的准确性 夏普队列；2)研究衍生数字生物标记物与疾病进展的关系 和认知衰退；以及3)调查重复测量数字生物标记物的能力 跟踪疾病进展。该项目将为非侵入性数字技术的使用提供必要的见解 提高检测和跟踪认知和功能状态纵向变化的能力的生物标志物 并将为未来更大规模的关键研究奠定基础。

Alzheimer’s disease (AD) is marked by progressive neuropathological changes that begin decades before cognitive and functional symptoms, and thus efforts have been focused on developing innovative tools and biomarkers for early identification of pre-dementia stages. To date, clinical ability to identify those with pre-dementia stages of AD has been limited and requires expensive (amyloid PET) or invasive (lumbar puncture) testing. However, subtle changes in connected speech may be detectable years before overt disease symptoms present. Our team has developed an approach that uses machine learning and natural language processing combined with advanced acoustic phonetic and lexical-semantic analyses. Preliminary data show promise in identifying AD biomarker status and predicting 2-year cognitive progression. In the proposed study, we leverage our success in collecting cerebrospinal fluid (CSF) biomarkers, neuroimaging and detailed cognitive phenotyping combined with audio recordings of participants in the Brain Stress, Hypertension and Aging Research Program cohort. This cohort, now in its third year of follow-up, consists of 400 individuals 50 years or older with normal cognition or mild cognitive impairment. We plan to extend this cohort of 400 participants for 3 more years to collect additional waves of voice recordings, cognitive assessments, follow-up CSF biomarkers and neuroimaging. Our overarching hypothesis is that the derived novel features reflecting poor lexical- semantic connectedness or acoustic perturbations are significantly different between biomarker-positive and -negative participants, have better diagnostic performance with regards to the ATN framework than traditional cognitive tests and can track disease progression. The Specific Aims are: 1) Determine the accuracy of the derived digital biomarkers in detecting in-vivo AD pathology and ATN classification in the B- SHARP cohort; 2) Investigate the association of the derived digital biomarkers with disease progression and cognitive decline; and 3) Investigate the ability of repeated measurement of the digital biomarkers to track disease progression. This project will provide needed insight into the use of non-invasive digital biomarkers to improve the ability to detect and track longitudinal changes in cognitive and functional status in AD and will set the foundation for a future larger pivotal study.