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

> **NIH NIH R44** · EVON MEDICS, LLC · 2022 · $1,245,116

## Abstract

ABSTRACT
We propose to evaluate and optimize the portable, home-based product – the Computerized Olfactory Training
Program (COT) – as a disease modifying intervention for prevention of progressive cognitive decline and
progressive dementia in early Alzheimer's Disease (AD). The COT uses validated neuroprotective olfactory
stimulants to intensely engage the primary and secondary olfactory cortices, with stimulation parameters that
overcome olfactory habituation, paired with computerized olfactory cognitive training tasks that synergistically
enhance the same brain regions; with the goal of increasing structural and functional resilience to AD
progression. Phase I research and development met or exceeded stated technical milestones: COT
intervention led to increased olfactory and cognitive functions 6 and 12 months later in ApoE4 carriers with mild
cognitive impairment and early dementia. Among completers of 12-month follow-up visit, COT blunted
trajectory in shrinkage of the entorhinal cortex and the hippocampus. Furthermore, the acute effects of odorant
molecules in the COT in regulating sleep disruptions and emotional reactivity adds to a potential value of COT
for treatment of behavioral dysfunctions in advanced AD. Alzheimer’s disease is a major public health crisis
both in the United States and worldwide. Hitherto, no therapeutic has demonstrated significant effectiveness in
modifying progression from early stages to advanced stages of AD. Most putative disease modifying
therapeutics targeting various steps of amyloid biosynthesis and amyloid beta (Aβ) accumulation have either
failed to reverse cognitive decline or worsened cognitive decline in Phase III clinical trials. However,
neuroscience evidence that AD pathology progresses early, over several decades in the olfactory brain
regions, before emergence of progressive, irreversible cognitive decline and dementia, as well as experimental
and clinical findings that olfactory compromise accelerates the progression of AD, provide solid premise for
targeting olfactory structure and function in the modification of AD progression. The success of use of enriched
odor environment in reducing aggregation of pathological neurofilaments in animals spurred high hopes for
translation of olfactory training (OT) into treatment of AD in humans. Unfortunately, lack of innovative
approaches to sustain olfactory engagement sufficiently to influence functional and structural plasticity in
clinical populations, hindered the translation of OT into an AD intervention. We built an innovative olfactory
treatment delivery system for home use; established a proprietary regimen of safe neuroprotective plant
odorant extracts and stimulation parameters that overcome odorant habituation in the primary olfactory cortex;
and created a synchronized App to simultaneously administer olfactory cognitive training tasks that
synergistically target the same brain regions being stimulated by the odorants. This breakthrough product...

## Key facts

- **NIH application ID:** 10399659
- **Project number:** 5R44AG061981-04
- **Recipient organization:** EVON MEDICS, LLC
- **Principal Investigator:** Charles Chiedu Nwaokobia
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,245,116
- **Award type:** 5
- **Project period:** 2018-09-30 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10399659

## Citation

> US National Institutes of Health, RePORTER application 10399659, Development and Evaluation of Computerized Olfactory Training Program (COT) for Cognitive Decline in Early Alzheimer's Disease (AD) (5R44AG061981-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10399659. Licensed CC0.

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