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

项目总结 申请人寻求K99/R00奖项，以实现专注于集成成像的研究独立性 和数字生物标记物，以检查阿尔茨海默病和相关的早期认知和精神症状 痴呆症。为了实现这一目标，申请者将接受对其独立性至关重要的三个领域的培训： (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，以及(3) 口语的认知特征。她还将接受她的专家指导团队的指导， 有辅导初级学者到完全独立，并获得全面培训的既定记录 通过一个详细的训练计划。她的研究将考察区域tau沉积和 鉴于阿尔茨海默病病理和临床证据，特定领域的认知能力下降 这表明情景记忆和语义记忆在发病前几年都是脆弱的。 痴呆症。在K99阶段，她将研究区域tau沉积如何与间歇性和 由Aβ临床正常(CN)、AβCN和Aβ轻度组成的两大队列中的语义记忆下降 认知障碍(MCI)个体。情景记忆和语义记忆将通过传统的 神经心理测试分数以及从认知的创新口语特征提取 面对面神经心理评估的录音。本研究的目的是，结合培训 而她将得到的指导，将使她在R00阶段为独立做好准备。在R00阶段， 她将研究区域tau沉积与评估的特定领域认知功能下降之间的关系。 通常是通过智能手机，一个越来越普遍的平台。具体地说，她将口头管理 基于移动认知测试和情绪评估，每3个月对Aβ-CN、AβCN和 一个βMCI个人的tau PET数据。情景记忆和语义记忆将由神经心理学测量 从真实世界中捕获的结构化响应中提取的分数和口语特征。因此， 这项提议的K99和R00阶段测试了总体假设，即Tau沉积发生在 大脑与特定领域的认知衰退有关。这一知识将提高阿尔茨海默氏症的准确性 此外，还应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R01应用，该应用集成了多模式成像和 从被动收集的非结构化语音记录中提取的口语特征，最大限度地 生态有效性，将参与者负担降至最低。这种方法也适用于阿尔茨海默病 以及更广泛的相关痴呆症。因此，K99/R00奖项将为申请者提供一个平台 开始独立的职业生涯，使用多模式成像和真实世界评估来理解认知 阿尔茨海默病和相关痴呆症的精神症状。

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.