Project Summary
This K23 application presents a training and research program that will support the applicant on a path towards
becoming an NIH-funded independent investigator focused on understanding the neurobiology of the olfactory
system in Alzheimer’s disease (AD). Training: The activities in this application build on the candidate’s prior
clinical neuropsychology training and research experience and are set in a resource-rich environment that will
foster his development of expertise in 1) principles of functional imaging in AD, 2) mechanisms and neural
circuitry of the olfactory system, 3) biostatistics and psychometrics, and 4) responsible conduct of research.
These training goals will be supported by a combination of didactics, formal advisory plans, and hands-on-
practicum throughout the award period. Under the guidance of his primary mentor, Dr. Davangere Devanand,
his co-mentor Dr. Terry Goldberg, scientific advisors (Drs. Gaurav Patel, Prasanna Karunanayaka, Mark
Albers, Jonas Olofsson, and Scott Small), and peer mentor (Dr. Jonathan Overdevest), the candidate will
acquire advanced skills in neuroimaging methodologies, olfactory evaluations, and AD biomarker mechanics
that will be directly applied to this proposal. Research: The overarching goal of the research to be carried out in
this application is to determine the neural mechanisms underlying odor memory deficits, and to define the
relationship between odor memory and AD biomarkers using a new process-pure variant of an odor memory
test. There is an urgent and unmet need to develop tools for enhancing early detection of AD. Olfaction and
memory are systems in which impairments develop during initial stages of AD. Odor memory, which combines
these two systems, has potential for improving upon the capabilities of existing tools which commonly measure
either system in isolation. Currently, the precise neural substrates of odor memory remain undefined. By
investigating the brain activation patterns involved in odor memory, there is promise for enhancing our ability to
identify individuals at risk for decline. This proposal will be the first to evaluate odor detection and odor memory
jointly within the same imaging paradigm. Aim 1 of the research project will examine fMRI task-related signal in
the olfactory cortex and medial temporal lobe during an fMRI odor memory procedure. Patients with AD,
patients with amnestic mild cognitive impairment, and cognitively intact older adults will undergo scanning. Aim
2 strives to establish the association of abnormal odor memory with apolipoprotein genotype and plasma tau
biomarkers. In Aim 3, the clinical utility of odor memory for differentiating groups (patients with AD, patients
with mild cognitive impairment, and cognitively intact older adults) will be compared against established odor
identification and verbal memory measures.