Odor memory and functional neuroimaging in cognitively impaired older adults and Alzheimer's disease - 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.
