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

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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.