Digital Accessible Remote Olfactory Mediated Health Assessments for Preclinical AD

项目摘要/摘要 目前有超过580万美国人受到阿尔茨海默病(AD)的影响，并带来经济负担 2020年预计为2700亿美元/年，预计在未来几年将至少增长四倍 几十年。已经开发出准确的生物标记物，表明AD病理存在15年 更早出现记忆症状。人们一致认为，发展的最佳战略 疾病修正疗法是在这一无症状的临床前阶段设计临床试验。海流 检测阿尔茨海默病15年临床前时期(记忆开始之前)个体的生物标记物 症状)都有局限性。它们主要是放射指标，价格昂贵，需要 容易旅行到偏远地区，或具有侵入性或昂贵。为了解决这一严重的未得到满足的医疗需求， 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诗歌所需的气味测试 算法在我们的第一阶段STTR拨款中。POEM算法设置个性化阈值以定义选择性 认知正常老年人个体嗅觉功能正常化的气味记忆丧失 采用气味辨别和气味识别试验。临床正常的有选择性气味的老年人 记忆缺陷在3个关键的AD风险因素中丰富：载脂蛋白E4，关键记忆中的神经退行性变和 大脑的嗅觉处理区域，认知功能随着时间的推移而显著下降。最近，这个 选择性气味记忆丧失被发现增加了HR&GT患者在接下来的4年内进展为MCI的风险； 3.3.为了充分发挥POEM算法的潜力，在这个第二阶段的应用中，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算法相结合，具有 最终目标是，这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的应用程序，并继续与Scentvation、 该公司采用创新的方法设计和制造气味输送设备，这些设备 可重复使用或和国际香精香料(IFF)谁已经开发出可邮寄的气味卡片 而且是一次性的。移动应用程序将通过指令和提示组织受试者的体验，并将收集 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, 由IFF开发的专有自然主义气味将被整合到这一电池中，以改善感知 不同文化和大陆的气味和表演的突出之处。随着……的发展 对于这些新产品，我们将寻求在临床和家庭环境中对它们进行现场测试。单独使用或一起使用 与其他探测不同大脑区域功能的非侵入性测量相结合，远程测试可以识别 认知正常的人存在阿尔茨海默病的病理和临床阿尔茨海默病的风险是必不可少的一步 开发和临床管理治疗方法，以应对日益严重的AD流行。

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.