Validating remote digital assessments for familial frontotemporal dementia

验证家族性额颞叶痴呆的远程数字评估

基本信息

批准号：
10448922
负责人：
Adam Mark Staffaroni
金额：
$ 237.14万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
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：
2022-05-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10448922
关键词：
3-Dimensional Accelerometer Adult Affect Aging Alzheimer&apos s Disease Alzheimer&apos s disease related dementia Assessment tool Behavioral Biological Markers Brain Health Registry C9ORF72 COVID-19 pandemic Cellular Phone Clinical Clinical Trials Clinical dementia rating scale Cognitive Cognitive aging Collaborations Data Data Set Dementia Detection Development Disease Disease Progression Early Diagnosis Enrollment Family Frontotemporal Dementia Funding Future Genes Geography Goals Gold Health Human Impaired cognition Individual Lead Light Longevity MAPT gene Magnetic Resonance Imaging Measurement Measures Methods Molecular Abnormality Monitor Motor Mutation Natural History Nerve Degeneration Neurodegenerative Disorders Neurologic Neuropsychological Tests Neuropsychology Observational Study Outcome Measure PGRN gene Parents Parkinson Disease Participant Pathogenicity Persons Plasma Prognosis Psychometrics Rare Diseases Recommendation Research Research Personnel Research Priority Response Latencies Sampling Severities Severity of illness Site Symptoms Testing Therapeutic Training Travel United States National Institutes of Health Validation Visit Visuospatial Work arm autosomal dominant mutation biomarker development brain magnetic resonance imaging cerebral atrophy clinical predictors cohort digital effective therapy follow-up healthy aging improved innovation kindred mobile application motor disorder mutation carrier neurofilament new therapeutic target novel online registry predictive modeling prognostication recruit remote grading research study smartphone Application standard measure therapeutic development treatment effect

项目摘要

PROJECT SUMMARY/ABSTRACT Frontotemporal Dementia (FTD) is a fatal neurodegenerative disease that presents with behavioral, cognitive, or motor dysfunction and has no effective treatments. About 20-30% of cases are familial (fFTD), caused by autosomal dominant mutations. Increasing numbers of novel therapeutics targeting these genetic abnormalities are entering clinical trials. A major barrier to fFTD therapeutic development is the lack of clinically meaningful outcome measures that can be easily collected and are sensitive to treatment effects at early stages of disease. Because fFTD is rare, participants are geographically dispersed and travel is another recruitment barrier for in-person clinical trials. To facilitate more inclusive clinical trials, investigators from the ARTFL/ LEFFTDS Longitudinal FTD (ALLFTD) consortium partnered with Datacubed Health to develop a novel smartphone application that enables remote testing of executive and motor functioning, domains affected early in fFTD. The goal of this proposal is to validate these innovative remote smartphone assessments for early detection, longitudinal monitoring, and prognostication of fFTD symptoms. To achieve this goal, the project will recruit two separate but related cohorts. The first is a cross-sectional cohort of 1,000 cognitively and functionally intact adults from across the lifespan enrolled through a collaboration with the NIH-funded Brain Health Registry (BHR). BHR participants will take the smartphone tests and online BHR clinical measures. The BHR cohort will be used to develop psychometrically robust composite scores and will be used to validate the scores in a healthy aging cohort. The second arm is a longitudinal clinical validation cohort of 400 participants from kindreds with known pathogenic fFTD mutations who will be recruited through the ALLFTD consortium, including 100 symptomatic and 150 presymptomatic fFTD mutation carriers and 150 noncarrier family controls. Participants in this cohort will complete the digital app assessments every six months for three years, along with comprehensive, annual in-person visits conducted through the parent ALLFTD study. Aim 1 will investigate the cross-sectional construct validity of the app composite scores by testing for associations with gold-standard measures of neuropsychological functioning, disease severity, and biomarkers of neurodegeneration. Aim 1 will also test whether the composites can detect early cross-sectional deficits in presymptomatic fFTD. Aim 2 will study the utility of these smartphone measures for longitudinal tracking of fFTD disease progression, and Aim 3 investigates whether these measures predict future clinical progression. If successful, this project will yield a scalable digital assessment tool for early detection, prognosis, and disease monitoring that could lead to more inclusive and powerful fFTD trials. Furthermore, as changes in executive and motor function are ubiquitous in neurological and aging cohorts, this app has broad applicability to study cognitive aging and associated conditions such as Alzheimer’s disease and related dementias.

项目摘要/摘要额颞痴呆（FTD）是一种致命的神经退行性疾病，表现为行为，认知，或运动功能障碍，没有有效的治疗方法。大约20-30％的病例是家庭（FFTD），由常染色体显性突变。针对这些遗传异常的新型治疗数量增加正在进入临床试验。 FFTD治疗发展的主要障碍是缺乏临床意义可以轻松收集并对早期治疗效果敏感的结果指标疾病。由于FFTD很少见，因此参与者在地理上分散，旅行是另一项招聘面对面临床试验的障碍。为了促进更具包容性的临床试验，ARTFL/的研究人员 Lefftds纵向FTD（AllFTD）财团与DataCubed Health合作开发了一种新颖智能手机应用程序可以远程测试执行和电机功能，域早期影响域在FFTD中。该提案的目的是早日验证这些创新的远程智能手机评估检测，纵向监测以及FFTD症状的提示。为了实现这一目标，该项目将招募两个单独但相关的队列。第一个是认知上的1,000个横截面队列通过与NIH资助的大脑合作，从功能上完整的成年人完整的成年人卫生注册表（BHR）。 BHR参与者将参加智能手机测试和在线BHR临床测量。这 BHR队列将用于发展心理稳健的综合分数，并将用于验证在健康衰老队列中的分数。第二臂是400名参与者的纵向临床验证队列来自具有已知病原FFTD突变的亲属，这些突变将通过Allftd联盟招募，包括100个有症状的和150个症状的FFTD突变携带者和150个非载波家族对照。该队列的参与者将每六个月完成每六个月的数字应用程序评估，持续三年通过父母AllFTD研究进行了全面的年度面向访问。目标1意志通过测试与神经心理功能，疾病严重程度和生物标志物的金标准测量神经变性。 AIM 1还将测试成分是否可以检测到早期横截面的定义 PRESYMPTOMOUS FFTD。 AIM 2将研究这些智能手机措施的效用，以进行纵向跟踪 FFTD疾病进展，AIM 3研究了这些措施是否预测未来的临床进展。如果成功，该项目将产生可扩展的数字评估工具，以供早期检测，预后和疾病监测可能会导致更具包容性和强大的FFTD试验。此外，随着变化高管和运动功能在神经和衰老队列中无处不在，该应用程序广泛适用研究认知衰老和相关疾病，例如阿尔茨海默氏病和相关痴呆症。