The Scent of Discovery: University Hospitals Researcher Explores What Smell Can Reveal About Brain Health

UH Research & Education Institute

What if a simple smell test could help identify changes in brain health years before memory problems appear?

Jennifer Villwock, MD

That question is driving the research of Jennifer Villwock, MD, Vice Chair of Research in the Department of Otolaryngology and Head and Neck Surgery at University Hospitals and Professor of Otolaryngology at Case Western Reserve University School of Medicine (CWRU SOM). A fellowship-trained rhinologist and anterior skull-base surgeon, Dr. Villwock studies how patterns in a person's sense of smell may offer new clues about cognitive health and the risk of neurodegenerative diseases such as Alzheimer's disease.  

Researchers have long known that changes in smell can occur years before symptoms of neurological conditions become apparent. Because the olfactory system is closely connected to areas of the brain involved in memory and cognition, sense of smell may be one of medicine’s most underused tools for understanding brain health.

Yet, despite decades of evidence connecting olfactory dysfunction to Alzheimer's disease, Parkinson's disease and traumatic brain injury, smell testing has not become part of routine neurological assessments. Dr. Villwock hopes to change that.

Like many physician-scientists, her research begins with questions that emerge from patient care.

“Most of my research endeavors are rooted in a desire to find better explanations or solutions when it seems like there should be a better way,” says Dr. Villwock. “We need to stay curious and pursue high impact areas of investigation so we can transform the lives of our patients through discovery.”

“Most of my research endeavors are rooted in things I see that don’t make sense or that we, as scientists, don’t have a better explanation for,” says Dr. Villwock. “We need to investigate more and find better ways to help patients through discovery.”

That mindset led her to question how olfactory function is measured and whether patterns in olfactory performance might reveal additional clinically meaningful information.

Making Smell Testing More Accessible

A central part of that work is the Affordable, Rapid, Olfactory Measurement Array (AROMA), a smell test Dr. Villwock developed in response to limitations she saw in existing approaches.

Traditional olfactory tests can be expensive and may use relatively simple chemical compounds that do not fully reproduce how people encounter and process scents in everyday life. AROMA was designed to be affordable, rapid and practical for real-world use.

The test uses familiar scents such as rose, lavender, peppermint, lemon, orange, cinnamon and clove. But Dr. Villwock is interested in more than whether someone can correctly identify a scent. She and her team are studying the patterns that emerge across different scents and concentrations and whether those patterns might provide important insights into overall health.

Those patterns could carry information extending well beyond the nose.

Searching for Earlier Signals of Cognitive Decline

One of the most promising areas of investigation is whether olfactory testing could help identify people at risk for cognitive decline before more noticeable symptoms emerge.

Dr. Villwock's ongoing research includes individuals across the cognitive spectrum, from people who are cognitively unimpaired to those with mild cognitive impairment or Alzheimer’s disease. Her team examines whether specific scents, concentrations or performance patterns correlate with established measures of brain health and cognitive function.

Researchers are also exploring whether smell-test results are associated with biological markers that currently require more complex and resource-intensive approaches, including Alzheimer’s disease plasma biomarkers and measurements of hippocampal volume on MRI scans.

Ultimately, Dr. Villwock wants to better understand not only what a person’s olfactory performance can tell us about their current brain health, but also whether it might provide insight into future cognitive health.

That question is becoming increasingly important as new treatments designed to slow Alzheimer’s disease progression become available. Earlier identification could help determine which individuals might benefit from further evaluation, participation in clinical trials or treatment at earlier stages of disease.

While smell testing is not currently used to diagnose Alzheimer's disease, researchers hope it will eventually serve as an accessible first step in identifying individuals who might benefit from further evaluation.

Expanding the Science of Smell at UH

Since joining UH as the inaugural Vice Chair of Research for the UH Ear, Nose & Throat Institute in 2025, Dr. Villwock has continued to expand the questions her research seeks to answer about the relationship between olfaction and systemic and neurologic health.

Her work is now extending further into the biology of Alzheimer’s disease with newly funded research examining the relationship between mitochondrial dysfunction and Alzheimer’s disease in preclinical models.

At the same time, she continues to explore how smell intersects with a wide range of health conditions. COVID-19 demonstrated on a global scale how viral illness can disrupt smell, while other research has connected olfactory changes to traumatic brain injury and movement disorders. Dr. Villwock is also interested in how sensory function may change during menopause and whether those changes could provide clues to differences in dementia risk between women and men.

Each question points toward a larger opportunity of transforming an easily accessible sensory system into a source of meaningful information about brain health.

“We don’t get a lot of smell training in medical school or even as residents and fellows,” says Daniel Simon, MD, President, Academic & External Affairs and Chief Scientific Officer, University Hospitals. “It’s so great that not only can we use the eye as a window on neurologic disease, but we should use smell as well.”

Looking Ahead

Important questions remain before olfactory testing can assume a larger role in neurologic screening or risk assessment. Researchers need to determine which patterns are most meaningful, how they relate to established biomarkers and whether they reliably predict future cognitive outcomes.

Still, the accessibility of smell testing creates an intriguing possibility.

Unlike advanced imaging and many biomarker tests, olfactory assessment has the potential to be inexpensive, noninvasive and scalable. If researchers can establish which olfactory patterns signal increased risk, smell testing could eventually help clinicians identify who might benefit from more comprehensive neurologic evaluation.