Development and Evaluation of Portable Compendium of Psychophysical and Physiological Tests for Alzheimer's Disease and Related Dementias (ADRD)

阿尔茨海默病和相关痴呆症（ADRD）便携式心理物理和生理测试纲要的开发和评估

• 批准号: 10699349
• 负责人: Charles Chiedu Nwaokobia
• 金额: $ 44.89万
• 依托单位: EVON MEDICS, LLC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10699349
• 关键词: Adopted; Adoption; Age; Age-associated memory impairment; Algorithms; Alzheimer' s disease related dementia; Alzheimer' s disease test; Anxiety; Businesses; Classification; Clinical; Clinical Research; Cloud Computing; Cognition; Cognitive; Cognitive aging; Collaborations; Communities; Dementia; Detection; Development; Devices; Diagnosis; Disease; Early Diagnosis; Early identification; Education; Elderly; Evaluation; Family member; Feedback; Fingers; Goals; Grant; Health Insurance Portability and Accountability Act; Health Personnel; Home; Impaired cognition; Impairment; Incentives; Individual; Infrastructure; International; Intervention; Language; Machine Learning; Marketing; Measurement; Measures; Memory; Motor; Neurodegenerative Disorders; Neurologist; Neurosciences; Odors; Olfactory dysfunction; Pathologic; Persons; Phase; Physicians; Physiologic Monitoring; Physiological; Population; Populations at Risk; Predisposition; Process; Provider; Psychophysics; Public Health; Reflex action; Regulatory Pathway; Research; Research Personnel; Risk; Sampling; Science; Self Efficacy; Sensorimotor functions; Sensory; Services; Severities; Signal Transduction; Small Business Innovation Research Grant; Smell Perception; Specificity; Staging; Surveys; Symptoms; Testing; Universities; Use Effectiveness; Validation; artificial intelligence algorithm; classification algorithm; clinical practice; cognitive task; comorbidity; cost; cost effectiveness; data communication; digital; early screening; experience; finger movement; follow-up; health determinants; large scale production; mild cognitive impairment; mobile application; motor disorder; motor impairment; normal aging; novel; older patient; patient population; phase 2 study; pilot test; portability; pre-clinical; primary care provider; product development; prognostic value; prognostication; prototype; remote monitoring; research clinical testing; satisfaction; screening; sensor; smell test; success; tool; user-friendly

ABSTRACT The Development and Evaluation of Portable Compendium of Psychophysical and Physiological Tests for Alzheimer’s Disease and Related Dementias (ADRD) is a project to develop an inexpensive, user-friendly, digital chemosensory-sensorimotor acquisition and processing device, with cross-cultural validity for home or office use for automated (a) staging of severity of age-related cognitive decline, (b) prognostication of people with subjective cognitive impairment at risk for progressive neurodegenerative diseases, and (c) remote surveillance of trajectory in motor and chemosensory markers of ADRD progression in elderly populations. Given that some decline in cognition is expected with advancing age, it is very challenging for elderly people to determine if their cognitive challenges are normal for age, or pathological. Similarly, our stakeholder survey of physicians who treat geriatric populations revealed that <10% of these physicians expressed self-efficacy in identifying early pathological cognitive decline in elderly patients complaining of subjective memory concerns, whereas more than 95% feel comfortable with diagnosing moderate or severe dementia. This is problematic, because, following onset of defining symptoms of dementia, ADRD progresses relentlessly, and no intervention has proven to reverse, or even slow the progression of dementia; whereas early identification may offer a more realistic opportunity for disease-modifying interventions to slow AD progression. Science has shown that AD presents early (even preclinically) with motor and sensory impairments, particularly olfactory dysfunctions. Therefore, an alternative approach to classification and prognostication of AD is to use precise quantitative measurements of sensory and/or motor dysfunctions. Indeed, psychophysical tasks of olfaction, such as odor identification tasks, have been found to predict AD development in normal aging, and to predict AD progression in mild cognitive impairments (MCI). But these olfactory cognitive tasks have not been adopted in practice or research for AD classification because of low specificity, challenges with interpretation, susceptibility to education, culture, and language biases, and absence of defined cut-off scores for classifying normal cognitive aging from MCI, or for prediction of MCIs who would soon develop dementia. Evon Medics, a small business specializing in olfactory neurostimulation, tested various olfactory tasks in their prototype – the Evon Medics Rapid Smell Test (EMRAST) – and determined that an olfactory sensorimotor impairment marked by loss of reflex reduction of sniff magnitudes to intense or unpleasant odorants, differentiated progressive MCI from normal cognitive aging, and quantitatively predicted MCI subjects that transitioned to dementia over 6- month follow-up. The goal of this SBIR Fast-Track proposal is to refine and evaluate composite scores derived from an extended portable version of EMRAST with psychophysical and physiological tasks of olfaction and measures of motor and sensorimotor functions, for prediction of ADRD among elderly people with memory concerns, prognostication of incipient dementia among people with MCI, and for remote monitoring of ADRD, which is a reimbursable service and a powerful incentive for adoption by health providers. The remote monitoring component also alleviates anxieties of family members of elderly persons who live independently. In the Phase I, we will (1) integrate all physiological sensors for olfactory sensorimotor and finger movements into the EMRAST prototype; (2) conduct a pilot testing on normal aging, MCI and early dementia patient populations for development of classification and prediction functions and algorithms; (3) integrate the Evon Medics HIPAA-compliant mobile App and cloud infrastructure into the product to enable seamless communication of data from the device to the user’s physician for remote monitoring of AD and modifiable health determinants of AD; and (4) examine fidelity of use and user/provider satisfaction. In Phase II, we will conduct large clinical validation testing to fine-tune the classification algorithms derived from Phase I. This will lead to automated interpretation, which the physicians desire. We will also advance regulatory pathway to clinical practice and establish the cost-effectiveness of use of EMRAST-Extended for remote monitoring of ADRD and associated comorbidities. Project success will be enhanced through strong collaborations between Evon Medics, Howard University and Johns Hopkins University investigators and AD stakeholders. The investigative team has significant experience in product and business development, ADRD clinical research, public health, and development and evaluation of olfactory devices. Completion of grant activities will lead to an optimized product to allow (1) clinical screening for early detection and prognostication of progressive neurodegenerative disease in people presenting with subjective cognitive complaints or age-associated memory complaints, (2) prediction of incipient dementia in people with mild cognitive impairment, and (3) broad international use as a language- and culture-independent tool for ADRD diagnosis and research.

抽象的 对心理物理和生理测试的便携式纲要的开发和评估 阿尔茨海默氏病和相关痴呆症（ADRD）是一个开发廉价，用户友好的项目 数字化学感应传感器的获取和处理设备，家庭或跨文化有效性 办公室使用自动化（a）与年龄相关认知能力下降的严重程度的分期，（b）人们的提示 主观认知障碍有进行性神经退行性疾病的风险，（c）远程 轨迹轨迹的监视和addrd的化学感应标记在古老的人群中的监视。 鉴于预计随着年龄的增长，认知会有所下降，所以老年人的挑战是 确定他们的认知挑战是年龄还是病理。同样，我们的利益相关者调查 治疗老年人群的医师表明，这些医生中的<10％在 确定老年患者的早期患者认知能力下降，抱怨主观记忆问题， 而95％以上的诊断中度或严重痴呆症感到满意。这是有问题的， 因为，随着定义痴呆症状的发作，Adrd相对进展，没有 事实证明，干预可以逆转，甚至减慢痴呆症的进展。而早期识别可能 提供更现实的机会，用于改善疾病的干预措施，以减缓AD的进展。科学有 表明广告早日（甚至是促趋化的）有运动和感觉障碍，尤其是嗅觉 功能障碍。因此，AD的分类和提示的另一种方法是使用精度 感觉和/或运动功能障碍的定量测量。确实，嗅觉的心理物理任务， 诸如气味识别任务已经被发现可以预测正常衰老的AD发展，并预测 轻度认知障碍（MCI）的AD进展。但是这些嗅觉认知任务尚未采用 在实践或研究广告分类的研究中，由于较低的特异性，解释的挑战， 对教育，文化和语言偏见的敏感性以及缺乏分类的截止分数 MCI的正常认知衰老，或预测很快会发展痴呆症的MCI。 Evon Medics，a 专门从事嗅觉神经刺激的小型企业，在其原型中测试了各种嗅觉任务 - Evon Medics快速气味测试（EMRAST） - 确定标记的嗅觉感觉运动障碍 通过减少反射量的嗅觉减少到强烈或不愉快的气味，分化的进行性MCI 从正常的认知衰老和定量预测的MCI受试者，这些受试者过渡到6-- 一个月随访。此SBIR快速曲目建议的目的是完善和评估得出的复合分数 从扩展的便携式版本的Emrast，具有嗅觉的心理物理和物理任务和 运动和感觉运动功能的度量，以预测老年人的ADRD 担心，促使有MCI患者的初期痴呆以及对ADRD的远程监控， 这是一项可偿还的服务，也是卫生提供者采用的强大动力。遥控器 监视组件还减轻了独立生活的老年人的家庭成员的动画。 在第一阶段，我们将（1）集成了所有物理传感器的嗅觉和手指运动 进入弹药原型； （2）对正常衰老，MCI和早期痴呆患者进行试验测试 开发分类和预测功能和算法的种群； （3）整合了evon 符合HIPAA的MELECICS HIPAA的移动应用程序和云基础架构进入产品，以使无缝 从设备到用户物理的数据进行通信，以远程监视AD和可修改 健康确定广告； （4）使用使用和用户/提供商满意度检查保真度。在第二阶段，我们将 进行大量的临床验证测试，以微调从第一阶段得出的分类算法 导致医生想要的自动解释。我们还将迈向监管途径 临床实践并确定使用emrast扩展的用于远程监视的成本效益 ADRD和相关的合并症。通过之间的强大合作将增强项目成功 埃文医务人员，霍华德大学和约翰·霍普金斯大学的调查人员和广告利益相关者。这 调查团队在产品和业务开发方面拥有丰富的经验，Adrd临床研究， 公共卫生以及嗅觉设备的开发和评估。赠款活动的完成将导致 优化的产品允许（1）临床筛查以进行早期检测和进行性筛查 神经退行性疾病在出现主观认知投诉或与年龄相关的人中 记忆投诉，（2）轻度认知障碍患者的初期痴呆预测，（3）广泛 国际用作ADRD诊断和研究的语言和文化独立的工具。