Olfactory dysfunction in Parkinson-plus syndromes: A comparison among themselves and controls

INTRODUCTION

Neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease (PD), often exhibit smell dysfunction even in their early stages.^[1] In fact, it helps differentiate PD from other Parkinson’s plus syndromes, such as progressive supranuclear palsy (PSP).^[2] In addition, smell testing is useful in recognizing PD even in its preclinical stages, and patients are oblivious to smell dysfunction until they undergo formal testing.^[2,3] In PD, Lewy bodies accumulate in the olfactory pathway, from the olfactory bulb to the higher olfactory centers, resulting in olfactory dysfunction.^[4] Another reason for olfactory dysfunction in PD is alpha-synuclein aggregation in different regions of the brain.^[5] Multiple system atrophy (MSA), a synucleinopathy, can cause smell dysfunctions.^[6] In PSP, degeneration also occurs in the insular region of the primary olfactory region.^[7] Hence, smell dysfunction may occur in patients with PSP.

There are numerous methods of testing olfaction in humans, like the University of Pennsylvania Smell Identification Test (UPSIT), the Brief-Smell Identification Test, the Indian Smell Identification Test, and the Sniffin’ 12 and Sniffin’ 16 odor identification tests.^[8,9] Although the results of smell testing may vary among individuals depending on the language and place of residence,^[10] UPSIT is quite sensitive and specific^[11] and is valid for testing neurological patients.^[8] As per previous records, UPSIT is also valuable for the regional population.^[12]

In this study, the authors assessed patients with Parkinson-plus syndromes to evaluate smell dysfunction, if any, and compared them with their age- and sex-matched healthy controls.

MATERIALS AND METHODS

In this observational study, the clinicians studied patients with Parkinson-plus syndrome coming outdoors as well as age- and sex-matched healthy controls (who gave their consent for the study) in the Department of Neurology of the institute from August 2020 to October 2023. For this study, the controls were patient attendants.

RESULTS

Table 1 depicts the demographic and clinical parameters of the Parkinson-plus syndrome patients and the controls. The investigators tested the age, sex, and education status for normality using the Shapiro–Wilk test and found skewness and kurtosis of −0.162 and −1.337, respectively, for age, 2.295 and 3.792, respectively, for sex and −0.487 peanut and −0.226, respectively, for education in patients with MSA. The similar values for the PSP patients were 0.710 and −0.159, respectively, for age, 0.571 and −1.934, respectively, for sex and 0.197 and −0.373, respectively, for education.

The mean total UPSIT score of the right side was 13.00 ± 3.96 for MSA patients and 12.00 ± 5.07 for PSP patients, while it was 29.73 ± 3.23 for the controls, and p-value between MSA and controls as well as that between PSP and controls was <0.001. However, the P-value between MSA and PSP was 0.770. For the left side, the mean total UPSIT score was 13.00 ± 3.68 for MSA patients, 12.06 ± 5.04 for PSP patients, and 29.90 ± 3.45 for the controls and p-value between MSA and controls, and that between PSP and controls was <0.001. p-value between MSA and PSP on the left side was 0.796. Table 2 depicts the values of different odors on the right side and the comparison between MSA and PSP and between cases and controls. Table 3 shows similar values on the left-hand side.

For MSA patients, the relationship between disease duration and UPSIT score gave a beta value of −0.565 and a P-value of 0.035 on the right side and a beta value of −0.635 and a P-value of 0.015 on the left side. Similar values for people with PSP were a beta of −0.299 and P-value of 0.261 on the right side and a beta of −0.264 and P-value of 0.323 on the left side.

Among different odors, MSA as well as PSP patients were not able to significantly identify many odors in both nostrils compared to healthy controls [Tables 2 and 3].

DISCUSSION

The mean UPSIT scores of patients with both MSA and PSP were significantly higher than those of the age- and sex-matched controls, indicating that these disorders impair an individual’s ability to smell. This is in contrast to previously reported literature, which suggests that normosmia, or very little impairment of smell, is a characteristic feature of PSP.^[15-18] Nevertheless, some previous researchers have reported smell dysfunction in PSP, similar to our observations.^[19,20] Similar to PSP, MSA patients do not conventionally suffer from olfactory dysfunction, contrary to what we observed in the present study.^[21,22]

In our study, we did not observe significant differences in the mean UPSIT scores of patients with MSA and PSP, in contrast to some previous studies that observed that MSA may alter smell detection ability more often than PSP.^[23,24] However, some studies have identified no significant differences in olfaction between MSA and PSP.^[21]

Although rare, these findings led a previous study to conclude that olfactory testing may not be an accurate biomarker for differentiating between PD and atypical Parkinsonism.^[25]

Among different odors, MSA patients were not able to significantly identify many odors in both the nostrils compared to healthy controls and the ability to identify many odors was conspicuously less in PSP patients as compared to the control population [Tables 2 and 3]. Although we do not have values of Parkinson-plus syndrome patients for similar comparison, previous studies on PD patients found similar results with the difference of some odors (menthol, orange, and coconut to be the most differentiating and turpentine, grape, and grass were the least discriminating in one study, and bubble gum, menthol, mint, banana, clove, coconut, onion, grape, powder, coffee, cinnamon, strawberry, petrol, cedar, apple, orange, watermelon, grass, smoke, pine, raspberry, soap, natural gas, and rose to be the most differentiating in another study) that our patients could identify.^[12,26] Although PSP patients could not identify most of the odors that MSA patients were unable to identify, they were able to identify a few more smells such as those of bubble gum, cherry, dill pickle, natural gas, and peanuts. Therefore, there may be some differences between MSA and PSP patients with regard to the number and type of smells that these two groups of patients can recognize.

In previous studies, the mean UPSIT score for controls was 24– 28 and the mean score for PD was 14–20, and our study had a more or less similar value for controls (29.73 ± 3.23) and the value for MSA in our study was 13.00 ± 3.96, and that for PSP was 12.00 ± 5.07. These values showed significant impairment in our MSA and PSP patients, similar to those found in PD patients in previous studies.^[12,27,28] These values showed greater impairment in smell identification in our patients with MSA and PSP compared to those of PD patients in previous studies.

The duration of the disease did not significantly alter the mean UPSIT scores of patients with PSP and MSA in the present study, similar to a previous study on PSP.^[19] In PD, the disease duration does not affect the results of smell testing.^[9]

CONCLUSION

Hence, patients suffering from Parkinson-plus syndromes (PSP and MSA) have significantly impaired olfaction compared to age- and sex-matched healthy controls, but the differences between the PSP and MSA groups may not be significant. In addition, disease duration did not affect the UPSIT scores of patients with MSA and PSP. These findings may thereby help in differentiating Parkinson-plus patients and controls based on their olfaction but not to that extent between MSA and PSP. Also, the smell dysfunction in these patients may be independent of the duration of disease in these patients.