Losing sense of smell can predict MS relapse-independent progression

Losing the sense of smell is associated with a higher likelihood of worse disease outcomes for people with multiple sclerosis (MS), according to a six-year follow-up study.

Specifically, patients who are getting worse at identifying and discriminating odors are at higher risk of disability worsening, relapse-independent MS progression, and cognitive impairment.

However, this decline in smelling ability was not associated with a higher likelihood of a disease relapse but it resembled the course of nerve cell damage in MS.

These findings “substantiate the role of olfactory DI [discrimination and identification] as a marker of slow progression and disability accumulation,” researchers wrote.

The study, “Odor discrimination and identification as a biomarker of long-term disability worsening in multiple sclerosis,” was published in the Multiple Sclerosis Journal.

Losing the sense of smell can happen in several neurological diseases

Loss of the sense of smell is a feature of several neurological diseases, including MS, which is characterized by the progressive loss of the protective sheath around nerve fibers, or axons. Smelling impairments can affect two major stages of smell perception, called “cable functions” and “processing functions.”

While the first stage is related to processes related to the transmission of odor information, the second is more related to the evaluation and processing of odors, and involves several brain regions, including the amygdala and the orbitofrontal cortex. These regions are known to be affected by different disease-associated processes, such as the neuroinflammation and neuroaxonal degeneration that contribute to MS.

As such, the ability to identify and discriminate odors, as measured by the olfactory DI score, has been suggested as a biomarker of neurodegeneration in MS. However, “to date, there is no long-term (up to 6 years) observational data on olfactory DI in MS,” the researchers wrote.

In the study, a team of researchers at the Medical University of Vienna, in Austria, investigated whether changes in the ability to identify and discriminate odors were a predictor of long-term disease course.

They looked at data from 92 adults (74 women and 18 men) with relapsing MS who were followed for at least six years at a single MS clinic. Their mean age was 35.7 years at the study’s start (baseline), and they had been living with MS for a median of 5.3 years.

Study set out to find link between olfactory sense and time to first relapse

The study’s main goal was to assess the link between odor DI, as measured by the extended version of the Sniffin’ Sticks test, and time to first relapse.

Secondary goals included potential associations between DI and time to disease worsening, as assessed by six-month confirmed score worsening in the Expanded Disability Status Scale (EDSS); time to cognitive deterioration; and time to progression independent of relapse (PIRA).

PIRA was defined as either six-month confirmed EDSS worsening or cognitive decline without the occurrence of a relapse in the month before or after.

At last follow-up, 49 patients (52.1%) had experienced disability worsening after a mean of 3.1 years, and 38 patients (40.4%) showed cognitive deterioration, as assessed by the Symbol Digit Modalities Test (SDMT), after a mean of 2.6 years.

Disease progression, assessed by PIRA, was seen in 27 patients (28.7%) after a mean of 3.4 years, and relapses occurred in 63 patients (67%) after a mean of two years.

At baseline, the mean olfactory DI was 27.8 points. The test’s maximum score is 32 and reflects optimal odor DI, while lower scores are associated with impaired ability to identify and discriminate odors. The olfactory DI significantly decreased, or worsened, to 27.5 after one year, and continued to decrease until the sixth year (26.3).

Older age, longer disease duration, and worse baseline EDSS and SDMT scores were significantly associated with lower olfactory DI, or poorer sense of smell, at baseline.

Patients experiencing worsening disability during follow-up showed significantly lower mean DI scores than those with stable disease by year two (26.4 vs. 27.9) and six (25.1 vs. 27.2).

Greater DI score differences, by about nearly three points, were detected between patients with and without PIRA, and those with and without cognitive decline at several time points.

DI scores found not linked to relapse occurrence

DI scores dropped significantly more over time among patients with disability worsening, PIRA, and cognitive decline than among those not experiencing these negative outcomes.

However, no significant differences were seen in DI scores and their changes between patients with and without relapse.

Statistical models confirmed that a greater decrease in smelling ability was significantly associated with disability worsening and cognitive decline during follow-up.

Lower DI scores at the study’s start and a greater score drop at any timepoint were each independently and significantly associated with a higher risk of disability worsening, PIRA, and cognitive decline. No such links were found for risk of relapse.

Particularly, for each one-point drop in the DI score during follow-up, the risk of disability worsening and PIRA increased by about twofold, while the risk of cognitive decline increased by four times.

Overall, these findings highlight that “the DI capability of MS patients is deteriorating in a slow, progressive, and irreversible manner, strongly resembling the course of neuroaxonal degeneration,” the researchers wrote.

“The degree and speed of this deterioration is associated with age and disease duration, but also with EDSS worsening, cognitive deterioration and PIRA,” the team wrote, but not with relapse activity.