# Linking olfactory deficits to memory impairment and AD neurodegeneration

> **NIH NIH R01** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2021 · $791,645

## Abstract

ABSTRACT
Olfactory impairment may signal prodromal Alzheimer’s disease (AD). We currently do not have an established
model that can be tested, in vivo, relating AD neurodegeneration to specific functional deficits in olfaction and
memory. This significant knowledge gap impedes the development of functional imaging markers for the
evaluation and diagnosis of AD.
We have developed several olfactory fMRI paradigms that can probe the dysfunctions in brain regions where
early stage AD neurodegeneration occurs. Our preliminary data suggest an AD neurodegeneration-to-function
model. We hypothesize that progressive neurodegeneration in MCI disrupts the connectivity of the olfactory
network (ON) to the default mode network (DMN) via the Hippocampus, leading to early deficits in olfaction
followed by memory impairment. Our research is designed to test this hypothesized model using functional
connectivity (FC; synchrony among brain regions) in resting state fMRI and effective connectivity (EC; directed
interactions between brain regions) during olfactory task fMRI; neurodegeneration will be evaluated by volumetric
MRI (vMRI).
Aim 1: Determine age-related changes in the ON-DMN network in cognitively normal subjects.
Aim 2: Determine changes in the ON-DMN network in mild cognitively impaired (MCI) subjects.
Aim 3: Explore the relationships between progressive changes in the ON-DMN network, and cognitive
 decline in MCI subjects
The over-arching goal of the proposed research will be to rigorously test an AD neurodegeneration model that
answers two fundamental questions: a) How are odor-identification and odor-discrimination deficits in AD related
to memory impairment and neurodegeneration? and b) Do olfactory deficits and progressive disruptions to ON-
DMN connectivity signal the development of AD dementia? Research outcomes can provide numerous avenues
for improving olfactory testing as an AD marker. Olfactory tests, which target specific brain areas and processes
that are affected earliest in AD, could hold additional promise for early disease detection and prevention in other
neurodegerative disease, such as Parkinson’s disease.

## Key facts

- **NIH application ID:** 10297048
- **Project number:** 1R01AG070088-01A1
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** Prasanna Rasika Karunanayaka
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $791,645
- **Award type:** 1
- **Project period:** 2021-08-15 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10297048

## Citation

> US National Institutes of Health, RePORTER application 10297048, Linking olfactory deficits to memory impairment and AD neurodegeneration (1R01AG070088-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10297048. Licensed CC0.

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