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

基本信息

批准号：
10370535
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
项目类别：
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/10370535
关键词：
Alzheimer&apos s Disease Alzheimer&apos s disease diagnosis Alzheimer&apos s disease related dementia Amyloid Amyloid beta-Protein Area Award Biological Markers Brain Brain region Cellular Phone Clinical Clinical Trials Cognition Cognitive Cohort Studies Data Dementia Deposition Development Early Diagnosis Elderly Episodic memory Framingham Heart Study Future Goals Image 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 Semantics Senile Plaques Sensitivity and Specificity Speech Structure Temporal Lobe Testing Time Training Voice base career cognitive performance cognitive testing cohort dementia risk design digital 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

项目摘要

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K99/R00奖，以实现研究注册成像的研究和数字生物标志物检查阿尔茨海默氏病的早期认知和精神病症状及其相关的症状痴呆症。（1）阿尔茨海默氏病的纵向研究设计和分析，（2）淀粉样蛋白和tau宠物成像，以及（3）认知的口语特征。拥有指导初级学者以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。鉴于阿尔茨海默氏病的病理和临床证据，领域特异性的认知能力下降收集到建议，但情节记忆和语义记忆都是脆弱的Youars 痴呆症。两个大型队列的语义记忆下降，包括临床正常（CN），Aβ+ CN和Aβ+轻度认知障碍（MCI）个体。神经心理学测试得分如 - 从中提取的认知的创新语言特征面对面神经心理学评估的记录。她将获得指导，将在R00阶段为她准备独立。 She WILL EXAMINE THE RELATION BETWEENAL TAU DEPOSITION And DOMAIN-SPECIFITIC COGNITIVE DECLINE ASSESSESSESSSESSESSESSSESSESSSESSSESSESSSESSSESSESSESSSESSESSESSESSESSESSES 经常通过智能手机，这个平台越来越多。每3个月对Aβ-CN，Aβ+ CN和具有tau PET数据的Aβ+ MCI。因此，从现实世界中捕获的结构化呼吸中提取的分数和口语特征。该提案的K99和R00阶段测试了Tau沉积物发生在大脑与特定于领域的认知下降有关。疾病的诊断是对有痴呆症的风险的筛查和监测 R00阶段将生成数据以支持将来的R01应用程序集成多模式成像和IND 口语功能从最大化的可传递的非结构化语音中提取生态有效性和最小化参与者负担也可以应用于阿尔茨海默氏病因此，相关痴呆症更广泛。使用多模式成像和REALD评估开始独立职业阿尔茨海默氏病和相关痴呆症的精神病症状。