Digital Accessible Remote Olfactory Mediated Health Assessments for Preclinical AD - Abstract
Over 5.5 million Americans are currently affected by Alzheimer's disease (AD) with an economic burden
estimated at > $250 billion/year in 2017 that is projected increase at least four fold over next several decades.
In spite of the dearth of pharmacological options to modify the course of the disease at present, the field has
developed accurate biomarkers that demonstrate that the pathology of AD is present 15 years of more prior to
the onset of memory symptoms. There is converging opinion at the national level and within pharmaceutical
companies that our best strategy to develop disease modifying therapies is to design clinical trials during this
asympomatic, preclinical period. The accurate biomarkers that detect individuals in the 15-year preclinical
period of AD (prior to the onset of memory symptoms) have limitations. They are largely radiological indicators,
which are expensive and require the subject to travel to a remote location. Moreover, with the advent of a
disease modifying therapeutic, screening the 75 million people above the age of 50 to determine who would
benefit from this therapy is prohibitively expensive. To address this critical unmet medical need, we developed
an algorithm of olfactory tests that functionally probe two vulnerable neural circuits with early signs of
pathology (olfactory and memory circuits). In clinically normal elderly individuals, who have undergone
longitudinal neuropsychological testing and radiographic phenotyping, the Percepts of Odor Episodic Memory
(POEM) algorithm identified clinical normal individuals with selective odor memory deficits, normalized to other
aspects of their individual olfactory function (odor discrimination and odor identification). Those clinically
normal elderly individuals with a selective odor memory deficit were enriched in the 3 key AD risk factors:
ApoE4, the strongest genetic risk factor for AD, evidence of neurodegeneration in a key memory and olfactory
processing area of the brain, and, most importantly, a significant decline in cognitive function over time. In
order to fully explore the potential of this finding, here we seek to expand our participant pool by creating a
digital olfactory battery that couples with the POEM algorithm, with the ultimate goal that this can be self
administered independently at home. To accomplish this goal, we have partnered with a leading digital health
company, the ADK group, to develop a mobile app and Scentovations, a company taking an innovative
approach to the design and manufacturing of odor delivery devices that are either reusable or disposable. The
mobile app will organize the subject's experience with instructions and cues, will collect the response data
generated in response to the tests, and will send it securely to a central location. In addition, proprietary
naturalistic odors developed by International Flavors and Fragrances will be incorporated into this battery to
improve the perceptual salience of odors and performance across different cultures and continents. Following
the development of this prototype, we will seek to validate it in both a clinical and home setting. Used alone or
together with other non-invasive measures that probe function of different brain regions, a remote test to
identify cognitively normal people harboring AD pathology and at risk of developing clinical AD is an essential
step to developing and clinically managing therapies that will impact the growing epidemic of AD.
