Regional tau deposition and digital assessment of cognition in preclinical AD and MCI

临床前 AD 和 MCI 中的区域 tau 沉积和认知数字评估

• 批准号: 10687981
• 负责人: Christina B Young
• 金额: $ 12.79万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10687981
• 关键词: Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease related dementia; Amyloid; Amyloid beta-Protein; Area; Award; Brain; Brain region; Cellular Phone; Clinical; Clinical Trials; Cognition; Cognitive; Cohort Studies; Data; Dementia; Deposition; Development; Digital biomarker; Early Diagnosis; Elderly; Episodic memory; Framingham Heart Study; Future; Goals; Impaired cognition; Individual; Knowledge; Language; Length; Location; Longitudinal Studies; Measures; Medial; Memory Loss; Mentors; Mentorship; Monitor; Moods; Multimodal Imaging; Neurobehavioral Manifestations; Neuropsychological Tests; Neuropsychology; Participant; Pathologic; Persons; Phase; Positioning Attribute; Positron-Emission Tomography; Research; Research Design; Risk; Semantic memory; Senile Plaques; Sensitivity and Specificity; Speech; Structure; Temporal Lobe; Testing; Time; Training; Voice; career; cognitive function; cognitive performance; cognitive testing; cohort; dementia risk; design; digital assessment; high risk; imaging biomarker; improved; in vivo; innovation; middle age; mild cognitive impairment; novel; pre-clinical; programs; protein aggregation; psychiatric symptom; response; screening; skills; smartphone application; tau Proteins; tau aggregation; treatment response; verbal

PROJECT SUMMARY The applicant seeks this K99/R00 award to achieve research independence focused on integrating imaging and digital biomarkers to examine early cognitive and psychiatric symptoms of Alzheimer’s disease and related dementias. To achieve this goal, the applicant will receive training in three areas critical to her independence: (1) longitudinal study design and analysis in Alzheimer’s disease, (2) amyloid and tau PET imaging, and (3) spoken language features of cognition. She will also receive guidance from her expert mentorship team who has an established record of mentoring junior scholars to full independence, and obtain comprehensive training through a detailed training plan. Her research will examine the relation between regional tau deposition and domain-specific cognitive decline given that pathological and clinical evidence of Alzheimer’s disease converges to suggest that both episodic and semantic memory are vulnerable years before the onset of dementia. During the K99 phase, she will examine how regional tau deposition relates to episodic and semantic memory decline in two large cohorts consisting of Aβ- clinically normal (CN), Aβ+ CN, and Aβ+ mild cognitive impairment (MCI) individuals. Episodic and semantic memory will be measured by traditional neuropsychological test scores as well as innovative spoken language features of cognition extracted from recordings of in-person neuropsychological assessments. This research aim, in combination with the training and mentorship she will receive, will prepare her for independence by the R00 phase. During the R00 phase, she will examine the relation between regional tau deposition and domain-specific cognitive decline assessed frequently through smartphones, an increasingly ubiquitous platform. Specifically, she will administer verbally based mobile cognitive tests and assessments of mood every 3 months for 1 year to Aβ- CN, Aβ+ CN, and Aβ+ MCI individuals with tau PET data. Episodic and semantic memory will be measured by neuropsychology scores and spoken language features extracted from structured responses captured in the real world. Thus, the K99 and R00 phases of this proposal test the overarching hypothesis that where tau deposition occurs in the brain relates to domain-specific cognitive decline. This knowledge will improve the accuracy of Alzheimer’s disease diagnosis as well as enhance the screening and monitoring of those at risk for dementia. Completion of the R00 phase will generate data to support a future R01 application integrating multimodal imaging and spoken language features extracted from passively collected unstructured voice recordings that maximize ecological validity and minimize participant burden. This approach can also be applied to Alzheimer’s disease and related dementias more broadly. The K99/R00 award will thus provide the applicant with a platform to launch an independent career using multimodal imaging and real-world assessments to understand cognitive and psychiatric symptoms of Alzheimer’s disease and related dementias.

项目摘要 申请人寻求这个K99/R 00奖，以实现研究的独立性，重点是集成成像 和数字生物标志物，以检查阿尔茨海默病的早期认知和精神症状， 痴呆症为了实现这一目标，申请人将在对其独立性至关重要的三个领域接受培训： (1)阿尔茨海默病的纵向研究设计和分析，（2）淀粉样蛋白和tau PET成像，和（3） 口语认知特征。她还将获得她的专家指导团队的指导， 有指导初级学者完全独立的既定记录，并获得全面的培训 通过详细的培训计划。她的研究将探讨区域性tau沉积与 阿尔茨海默病病理学和临床证据显示的特定领域认知功能下降 这表明，情节记忆和语义记忆在发病前几年都是脆弱的。 痴呆在K99阶段，她将研究区域性tau沉积与偶发性和 两个大型队列的语义记忆下降，包括Aβ-临床正常（CN）、Aβ+ CN和Aβ+轻度 认知障碍（MCI）患者。情景记忆和语义记忆将通过传统的 神经心理学测试成绩以及从 神经心理学评估的记录。本研究旨在结合培训 她将得到的指导，将为她在R 00阶段的独立做好准备。在R 00阶段， 她将研究区域性tau蛋白沉积与特定领域认知能力下降之间的关系， 通常通过智能手机，一个越来越普遍的平台。具体来说，她将口头管理 基于移动的认知测试和情绪评估，每3个月一次，持续1年，以Aβ- CN、Aβ+ CN和 具有tau PET数据的Aβ+ MCI个体。情景记忆和语义记忆将由神经心理学测量 从真实的世界中捕获的结构化响应提取的分数和口语特征。因此，在本发明中， 该方案的K99和R 00阶段测试了总体假设，即在Tau沉积发生的地方， 大脑与特定领域的认知能力下降有关。这些知识将提高阿尔茨海默氏症的准确性 疾病诊断以及加强对痴呆症高危人群的筛查和监测。完成 将生成数据，以支持未来的R 01应用程序， 从被动收集的非结构化语音记录中提取的口语特征， 生态有效性和最小化参与者负担。这种方法也可以应用于阿尔茨海默病 以及更广泛的痴呆症。因此，K99/R 00奖项将为申请人提供一个平台， 使用多模态成像和真实世界评估来了解认知能力， 以及阿尔茨海默病和相关痴呆症的精神症状。