A surprising shift in sniffing and odor perception could be a key sign of Parkinson’s disease

A novel test that evaluates both a person's odor description and their physical sniffing behavior may distinguish Parkinson’s disease from other causes of diminished smell perception. The research, published in npj Parkinson’s Disease, reveals that individuals with Parkinson’s exhibit a shift in odor perception, not merely a loss of smell.

Previous research indicates that early markers of Parkinson’s, such as altered odor perception, can appear years before motor symptoms manifest. While traditional smell tests are commonly employed to confirm a Parkinson’s diagnosis, they merely assess overall performance, failing to pinpoint the underlying cause. This can be problematic because smell loss is also frequently observed in healthy aging, viral infections, or sinus problems, making it challenging to determine whether poor test outcomes signal Parkinson’s or another condition.

Michal Andelman-Gur, a medical doctor and researcher involved in the study while working with Noam Sobel’s Weizmann Olfaction Research Group at the Weizmann Institute of Science, aimed to address this diagnostic uncertainty. "As a medical doctor, I have always been interested in neurological diseases," Andelman-Gur explained. "Observing the impact of these diseases firsthand during my work in the Neurology Department at Tel Aviv Medical Center fueled my interest in early detection."

"Smell loss may seem like a minor, common symptom, but in some cases, it can serve as an early warning sign of Parkinson’s disease, years before motor symptoms begin," Andelman-Gur added. "Our test aims to identify a specific pattern of smell changes associated with Parkinson’s disease, potentially enabling earlier detection and more timely intervention."

The study involved 94 participants, comprising 33 with Parkinson’s disease, 33 healthy controls, and 28 with smell loss unrelated to Parkinson’s. The groups were matched for age and sex, ranging from approximately 58 to 66 years old. Participants first underwent a standard clinical smell test assessing detection, discrimination, and identification capabilities on a 48-point scale.

Healthy controls scored a median of 30.5, while both the Parkinson’s group (16.5) and those with other types of smell loss (12.4) performed significantly worse. Even after adjusting for age, sex, and medication, the test could not differentiate between the Parkinson’s group and those with other forms of smell loss. Subsequently, participants smelled jars containing a pleasant lemon scent, an unpleasant fecal scent, or no odor.

They rated the intensity and pleasantness of each scent on a scale of 1 to 100. While those with non-Parkinson’s smell loss rated the pleasant odor's intensity at a median of 16 (compared to 78 for healthy controls), those with Parkinson’s rated it at 78, matching the healthy controls. However, both groups with Parkinson’s and smell loss rated the pleasant scent at a median of 50, indicating a specific alteration in how Parkinson’s patients perceive pleasantness.

To further characterize odor perception, participants rated 10 different chemical odors across 11 descriptive categories (e.g., sweet, spicy, burnt) on a 100-point scale. This generated a mathematical profile of each individual's odor perception. The researchers discovered that individuals with Parkinson’s shared a distinct pattern of odor perception, correlating more closely with other Parkinson’s patients than with healthy controls or those with non-Parkinson’s smell loss.

The study also measured involuntary sniffing behaviors using a nasal flow sensor. Healthy controls typically took longer, deeper sniffs for pleasant odors and shorter sniffs for unpleasant ones. In contrast, Parkinson’s patients showed sniffing patterns consistent with their specific odor perception profile. This research suggests that a shift in how Parkinson’s patients assign pleasantness to odors, rather than a generalized loss of smell, may serve as a valuable early diagnostic indicator.