Development and Evaluation of Computerized Olfactory Training Program (COT) for Cognitive Decline in Preclinical and Early Alzheimer's Disease (AD)

ABSTRACT The Development and Evaluation of Computerized Olfactory Training ProgramCOTfor Cognitive Decline in Preclinical and Early Alzheimer s DiseaseADis a project to develop a home based brain stimulation device for prevention of AD progression in preclinical and early ADThe success of enriched odor environment for reversal of AD pathology in animals spurred high hopes for translation of olfactory trainingOTinto prevention and treatment of AD in humansOT interventions are based on sniffing from different odorant bottles twice daily forweekswith a once weekly informal olfactory cognitive componentin which people are asked to subjectively rate how they felt their olfaction had improvedBut asking people to subjectively rank their olfactory abilities does not strictly train their olfactory brain structuresand having people sniff from bottles does not take into consideration the fact that olfactory structures differ in their thresholds for activation and desensitization to odor elementsAdaptation of olfactory structures to the odorants limits the extent of neuroplasticity gained from odor enrichmentAn alternative strategy is to use a portableprogrammedhome based device to administer olfactory psychophysical tasks while patients are being stimulated repeatedly with a large number of neurotrophic olfactory stimulantsusing neuroscience guided stimulation parameters to ensure sustained activation of all primary and secondary olfactory structuresThe small businessEvon Medics and Howard UniversityHUhave created a prototype called COTComputerized OT programto allow automated intensive enrichment of olfactory structuresThis proposal will further product development to allow broad COT implementation and commercializationwith customization to prevent progressive cognitive decline in early ADProject site is the Geriatric clinic at HUIn Aimwe will conduct comprehensive functional magnetic resonance imagingfMRIevaluation of enrichment molecules and stimulation parameters for maximal activation of the primary and secondary olfactory corticesPOC and SOCThe primary objective is to establish a treatment paradigm of burst frequencies and durationand interstimulation intervalsISIto extensively engage the POC and SOCtaking into consideration differences in patterns of activations and inhibition in these regionsThe second objective is to determine brain areas that are differentially activated by psychophysicale godor identification and memorytaskswhich will serve to optimize brain activities during passive stimulationsThe third of objective is to identify a proprietary regimen of the most neuroprotective olfactory stimulants to incorporate into the stimulation and cognitive programIn Aiman optimized COT product will be developedThe current prototype will be improved based on Aimto create atest readyCOT version that includes computerized psychophysical tasksThe psychophysical tasks that activate a region will be paired with stimulation parameterse gburst frequencyduration and ISIthat maximally activate that same regionUser testing of thetest readyCOT version will be conducted in patients with mild cognitive impairmentMCIto gather user feedback and guide further product optimizationIn Aimoptimized version of the COT will be implemented in MCI and early AD groups to demonstrate pilot effectiveness and cost effectivenesscompared to usual care and traditional OTImprovement in olfactory and cognitive functions will be primary outcomes of interestIn additiona cost analysis will assess the patient and health system costs associated with using COT compared to costs associated with the standard of care and OTPatient and caregiver satisfaction with COT will be assessedProject success will be enhanced through strong collaborations between Evon Medics and HU investigatorsThe investigative team has significant experience in product and business developmentAD researcholfactory neuroscienceand development and evaluation of AD interventionsCompletion of grant activities will lead to an optimized product to allow COT that overcome the drawbacks of traditional OT in prevention of cognitive decline in AD NARRATIVE The time is now to develop disease modifying interventions to treat or prevent development of AD in people with Mild Cognitive Impairmentand the olfactory systemsite of AD developmentoffers a unique opportunity to tackle AD early developmentWe propose to develop and optimize a novel computerized olfactory training program that uses a portableprogrammedhome based devicethe Computerized Olfactory TrainingCOTprogramto administer olfactory psychophysical tasks while patients are being stimulated repeatedly using neuroscience guided stimulation parameters to ensure sustained activation of all primary and secondary olfactory structuresCompletion of grant activities will lead to an optimized product to allow COT that overcome the drawbacks of traditional olfactory training in prevention of cognitive decline in AD