Digital Accessible Remote Olfactory Mediated Health Assessments for Preclinical AD

项目总结/摘要 目前，超过580万美国人受到阿尔茨海默病（AD）的影响，并带来经济负担 预计到2020年将超过2700亿美元/年，预计在未来几年内将增加至少四倍。 几十年已经开发了准确的生物标志物，其证明AD病理学存在15年。 更早出现记忆症状人们一致认为，发展的最佳战略 疾病修饰疗法是在这个无症状的临床前阶段设计临床试验。当前 在AD的15年临床前阶段（在记忆开始之前）检测个体的生物标志物 症状有局限性。它们主要是放射性指标，价格昂贵， 容易移动到遥远位置或者是侵入性或昂贵的。为了解决这一关键的未满足的医疗需求， 我们开发并测试了AROMHA基于网络的应用程序，该应用程序可以进行POEM所需的气味测试 算法在我们的第一阶段STTR赠款。POEM算法设置个性化的阈值，以定义选择性的 通过使每个个体的嗅觉功能正常化，在认知正常的老年个体中的气味记忆丧失 采用气味辨别和气味鉴别试验。临床正常的老年人，具有选择性气味 记忆缺陷在3个关键的AD风险因素中富集：ApoE 4，关键记忆中的神经变性， 大脑的嗅觉处理区，随着时间的推移，认知功能明显下降。最近这款 研究发现，选择性气味记忆丧失会增加未来4年进展为MCI的风险，HR > 3.3.为了充分发挥POEM算法的潜力，在第二阶段的应用中，我们寻求扩展 我们的AROMHA产品通过创建一个数字嗅觉电池，与POEM算法耦合， 最终目标是可以在家里独立管理。为了实现这一目标，我们将 在iOS和Android生态系统中开发独立应用程序，并继续与Scentovation合作， 公司采取创新的方法来设计和制造气味输送设备，这是 可重复使用的或国际香料和香水（IFF）谁开发的气味卡，是邮寄 一次性的。该移动的应用程序将组织受试者的经验与指示和线索，将收集 响应测试生成的响应数据，并将其安全地发送到中央位置。此外，本发明还提供了一种方法， 由IFF开发的专有自然气味将被纳入该电池，以改善感知 不同文化和大陆的气味和性能的显著性。随着 这些新产品，我们将寻求在临床和家庭环境中进行实地测试。单独或一起使用 与其他探测不同大脑区域功能的非侵入性措施一起， 认知正常的人携带AD病理和发展临床AD的风险是一个重要的步骤， 开发和临床管理将影响日益增长的AD流行病的疗法。

Project Summary / Abstract Over 5.8 million Americans are currently affected by Alzheimer's disease (AD) with an economic burden estimated at > $270 billion/year in 2020 that is projected to increase at least four fold over the next several decades. Accurate biomarkers have been developed that demonstrate that AD pathology is present 15 years of more prior to the onset of memory symptoms. There is converging opinion that the best strategy to develop disease modifying therapies is to design clinical trials during this asymptomatic, preclinical period. The current biomarkers that detect individuals in the 15-year preclinical period of AD (prior to the onset of memory symptoms) have limitations. They are largely radiological indicators, which are expensive and require the subject to travel to a remote location or are invasive or expensive. To address this critical unmet medical need, we developed and tested the AROMHA web-based app that conducts the odor tests needed for the POEM algorithm in our Phase I STTR grant. The POEM algorithm sets personalized thresholds to define selective odor memory loss in cognitively normal elderly individual by normalizing each individual's olfactory function using odor discrimination and odor identification test. Clinically normal elderly individuals with a selective odor memory deficit are enriched in the 3 key AD risk factors: ApoE4, neurodegeneration in a key memory and olfactory processing area of the brain, a significant decline in cognitive function over time. Recently, this selective odor memory loss was found to increase risk of progression to MCI over the next 4 years with a HR > 3.3. In order to fully realize the potential of the POEM algorithm, in this Phase II application we seek to expand our AROMHA products by creating a digital olfactory battery that couples with the POEM algorithm, with the ultimate goal that this can be self administered independently at home. To accomplish this goal, we will develop standalone apps in the iOS and Android ecosystems and continue working with Scentovation, a company taking an innovative approach to the design and manufacturing of odor delivery devices, that are reusable or and International Flavors and Fragrances (IFF) who has developed smell cards that are mailable and disposable. The mobile app will organize the subject's experience with instructions and cues, will collect the response data generated in response to the tests, and will send it securely to a central location. In addition, proprietary naturalistic odors developed by IFF will be incorporated into this battery to improve the perceptual salience of odors and performance across different cultures and continents. Following the development of these new products, we will seek to field test them in both clinical and home settings. Used alone or together with other non-invasive measures that probe function of different brain regions, a remote test to identify cognitively normal people harboring AD pathology and at risk of developing clinical AD is an essential step to developing and clinically managing therapies that will impact the growing epidemic of AD.