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.

摘要 心理生理测验便携式简编的研制与评价 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， 数字化化学感觉-感觉运动采集和处理装置，具有家庭或 办公室使用，用于自动化（a）年龄相关认知衰退严重程度的分期，（B）人群的统计 具有进行性神经退行性疾病风险的主观认知障碍，和（c）远程 监测老年人群中ADRD进展的运动和化学感觉标志物的轨迹。 考虑到随着年龄的增长，认知能力会有所下降，老年人在以下方面非常具有挑战性： 确定他们的认知挑战是正常的年龄，或病理。同样，我们的利益相关者调查 治疗老年人群的医生显示，<10%的医生表达了自我效能感， 在抱怨主观记忆问题的老年患者中识别早期病理性认知衰退， 而超过95%的人对诊断中度或重度痴呆感到满意。这是有问题的， 因为，在痴呆症的定义症状发作后，ADRD会无情地发展， 干预已被证明可以逆转，甚至减缓痴呆症的进展;而早期识别可能 为减缓AD进展的疾病改善干预提供了更现实的机会。科学已经 表明AD早期（甚至是临床前）出现运动和感觉障碍，特别是嗅觉障碍 功能障碍因此，AD分类和分类的另一种方法是使用精确的 感觉和/或运动功能障碍的定量测量。实际上，嗅觉的心理生理任务， 例如气味识别任务，已经发现可以预测正常衰老中AD的发展， 轻度认知障碍（MCI）的AD进展。但这些嗅觉认知任务并没有被采用 在AD分类的实践或研究中，由于低特异性，解释的挑战， 对教育、文化和语言偏见的敏感性，以及缺乏用于分类的确定的截止分数 MCI的正常认知老化，或用于预测即将发展为痴呆的MCI。Evon Medics，a 专门从事嗅觉神经刺激的小型企业，在他们的原型中测试了各种嗅觉任务- Evon Medics快速嗅觉测试（EMRAST）-并确定嗅觉感觉运动障碍明显 通过丧失对强烈或令人不快的气味的嗅闻幅度的反射减少，区分进行性MCI 从正常的认知老化，并定量预测MCI受试者过渡到痴呆超过6- 月随访。本SBIR快速通道提案的目标是完善和评估 从一个扩展的便携式版本的EMRAST与心理物理和生理任务的嗅觉和 运动和感觉运动功能的测量，用于预测有记忆的老年人中的ADRD 关注，MCI患者中早期痴呆症的诊断，以及ADRD的远程监测， 这是一项可报销的服务，也是对医疗服务提供者采用该服务的有力激励。远程 此外，监察部分亦可消除独居长者家人的忧虑。 在第一阶段，我们将（1）整合所有的嗅觉感觉运动和手指运动的生理传感器 在正常老化、MCI和早期痴呆患者中进行了初步测试 用于开发分类和预测功能和算法的群体;（3）整合Evon 将符合HIPAA标准的移动的应用程序和云基础架构整合到产品中， 将数据从设备传送到用户的医生，用于远程监测AD和可修改的 AD的健康决定因素;（4）检查使用的忠诚度和用户/提供者满意度。在第二阶段，我们将 进行大型临床验证测试，以微调来自第一阶段的分类算法。这将 导致医生所期望的自动化解释。我们还将推进监管途径， 临床实践，并建立使用EMRAST-Extended进行远程监测的成本效益 ADRD和相关合并症。项目的成功将通过以下方面的强有力合作得到加强： 埃文医生，霍华德大学和约翰霍普金斯大学的研究人员和AD利益相关者。的 研究团队在产品和业务开发、ADRD临床研究 公共卫生以及嗅觉装置的开发和评估。赠款活动的完成将导致 一种优化的产品，允许（1）临床筛查，以早期发现和证实进行性 存在主观认知主诉或年龄相关性的神经退行性疾病 记忆投诉，（2）轻度认知障碍患者早期痴呆的预测，以及（3）广泛的 作为一种独立于语言和文化的ADRD诊断和研究工具在国际上使用。