Olfactory Bulb Volume, Olfactory Sulcus Depth in Parkinson's Disease, Atypical Parkinsonism

Abstract

Background

About 70–90% of Parkinson's disease (PD) patients have olfactory deficits which is considered as pre‐motor symptom of PD. Lewy bodies have been demonstrated in the olfactory bulb (OB) in PD.

Objective

To assess the OB volume (OBV), olfactory sulcus depth (OSD) in PD and compare with progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and vascular parkinsonism (VP) patients and determine the cut‐off volume of OB that will aid in the diagnosis of PD.

Methods

This was a cross‐sectional, hospital based, single‐center study. Forty PD, 20 PSP, 10 MSA, 10 VP patients and 30 controls were recruited. OBV and OSD was assessed using 3‐T magnetic resonance imaging (MRI) brain. Olfaction was tested using Indian Smell Identification test (INSIT).

Results

The mean total OBV in PD was 113.3 ± 79.2 mm³ and 187.4 ± 65.0 mm³ in controls (P = 0.003) which was significantly lower in PD. The mean total OSD in PD was 19.4 ± 8.1 and 21.1 ± 2.2 mm in controls (P = 0.41) with no difference. The mean total OBV was significantly lower in PD as compared to that of PSP, MSA and VP patients. There was no difference in the OSD among the groups. The total OBV in PD had no association with age at onset, duration of disease, dopaminergic drugs dosage, motor and non‐motor symptoms severity but had positive correlation with cognitive scores.

Conclusion

OBV is reduced in PD patients as compared to PSP, MSA, VP patients and controls. OBV estimation by MRI adds to the armamentarium in the diagnosis of PD.

Parkinson's disease (PD) is an alpha‐synucleinopathy with selective neuronal loss in substantia nigra pars compacta (SNpc) and the presence of Lewy body inclusions within the affected neurons that are composed mainly of α‐synuclein. ¹ Apart from the classical motor symptoms of rest tremors, rigidity and bradykinesia, there are several non‐motor symptoms (NMS) in PD. These NMS include neuropsychiatric symptoms, sleep disorders, autonomic symptoms, gastrointestinal symptoms, sensory symptoms that include olfactory dysfunction. ² Olfactory dysfunction is the second most common feature of PD, following rigidity and akinesia. About 70–90% of PD patients have olfactory deficits which is independent of disease severity and duration. It can precede the motor symptoms by several months or even years and is considered as pre‐motor symptom of PD. ³ Post‐mortem studies have demonstrated the presence of Lewy bodies in the olfactory bulb (OB). Using magnetic resonance imaging (MRI), the volume of the OB (OBV) and olfactory sulcus depth (OSD) can be reliably measured. It has been suggested that the measurement of OBV can be helpful in the differential and early diagnosis of PD from the other atypical parkinsonian disorders. The present study was aimed to assess the OBV, OSD using the brain MRI in patients with PD and compare with progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and vascular parkinsonism (VP) patients and determine the cut‐off OBV that will aid in the diagnosis of PD.

Materials and Methods

Study Design

The study was a cross‐sectional, hospital‐based study conducted in the department of neurology of a quaternary care center for neurological disorders in south India.

Study Subjects

A total of 40 patients of PD, 20 patients of PSP, 10 patients of MSA, 10 patients of vascular parkinsonism and 30 age and gender‐matched controls were included in the study. PD was diagnosed as per the Movement Disorders Society criteria for PD, PSP as per the Movement Disorders Society criteria for PSP, MSA as per the Consensus criteria for MSA and VP as per the Winikates and Jankovic criteria. ⁴ , ⁵ , ⁶ , ⁷ The controls were recruited from the study hospital who were hospital employees, out‐patient department patient attendants who were voluntarily willing to participate after explaining the objective of the study. Patients and controls with significant medical comorbidities, other neurodegenerative diseases, local causes of olfactory dysfunction like recent head trauma, rhinosinusitis, Coronavirus disease 2019, MRI contraindications like MRI incompatible implants, and pacemakers were excluded. The study period was from April 2020 to April 2022 with a total duration of 24 months. Written informed consent was taken from the patients and the controls seeking their participation. No incentives were paid for the participation in the study. The study was approved by the institutional ethics committee (NO. NIMH/DO/IEC‐BS& NS DIV/2020/29‐04‐2020). The study was conducted according to the International Ethical Guidelines for Biomedical Research Involving Human Subjects.

Data Collection

Neurological Assessment

The sociodemographic details of the patients included age at presentation, age of onset, gender, duration of illness, educational qualification, socio‐economic status, comorbid illness, number of present and past medications with dose and duration of intake; clinical data—details about tremors, bradykinesia, rigidity, postural instability, falls, dysarthria, dysphagia, presence of anosmia, levodopa responsiveness, total levodopa equivalent dose (TLED) and neurological examination findings were recorded. The olfactory testing was done using Indian Smell Identification test (INSIT). INSIT include essences of 10 commonly used daily items as odorants and patients has to identify by sniffing the odorants. The total score is 10 and a score of ≤4 is considered as anosmia. ⁸ The Montreal cognitive assessment (MOCA) scale was used to assess the cognition. ⁹ The severity of motor symptoms was assessed using Unified Parkinson Disease Rating Scale (UPDRS) and staging of PD was done by the Modified Hoehn & Yahr (H&Y) scale. ¹⁰ , ¹¹ The non‐motor symptoms were assessed using the Non‐motor symptom assessment for PD scale (NMSS). ¹² The severity of PSP was assessed by Progressive Supranuclear Palsy rating scale (PSPRS) and clinical assessment of MSA patients was done using the Unified Multiple System Atrophy rating scale (UMSARS). ¹³ , ¹⁴

Radiological Assessment Using Brain MRI

The brain MRI was done by using a 3‐T system (Phillips Ingenia 3.0 T MR system) with standard conventional protocol with Coronal multiplanar reconstruction (MPR) or T2‐weighted spin‐echo sequences. Coronal 3D T2 weighted driven equilibrium gradient refocused sequence (DRIVE) were performed using TR/TE (2000/235 ms); section thickness, 1 mm; matrix 376 × 300 × 170 slices; FOV‐ 150 × 150 × 85 mm; and the in‐plane pixel resolution, voxel 0.4 × 0.5 × 1 mm. The Signal to Noise ratio was 1 and angulation was kept at 0°. The sections were angulated perpendicular to the anterior base of skull or cribriform plate.

Imaging Data Analyses

The bilateral OBV and the OSD were measured in all study subjects. An experienced neuroradiologist (KK) performed the OBV and OSD measurements who was blinded to the diagnoses. The anterior cribriform plate and the cerebrospinal fluid surrounding the OB were used as the markers to determine the boundaries of the OB. 3D Slicer software version 4.11.20210226 was used for the imaging data analysis (Fig. S1). OSD was measured by identifying the medial orbital gyrus and gyrus recti of the frontal lobe at the posterior plane of orbit, drawing a virtual tangent line from the lower end of the medial orbital gyrus connecting the lower end of the gyrus rectus and drawing a perpendicular line connecting this tangent line to the deepest point of the olfactory sulcus.

Statistical Analysis

Data were analyzed with Statistical Package for Social Sciences V26.0 (SPSS Inc, Chicago, IL, USA) and Microsoft Excel sheet. Categorical variables were expressed as frequency, percentage and continuous variables as mean with standard deviation. The normality of data was assessed using the Shapiro‐Wilks test. Student “t” test was used to compare the means between two groups. One‐way ANOVA were used for comparison of the means among the groups. Categorical variables were analyzed by Pearson's Chi‐Square test. Pearson correlation coefficient was used to compare the strength of association between the variables. A P‐value of <0.05 was considered significant. Receiver Operating Characteristic (ROC) curve analysis was done to evaluate the diagnostic accuracy of OBV in diagnosing PD. The area under the curve (AUC) was calculated to estimate the optimal cut‐off volume of the OB in diagnosing PD.

Data Sharing

Data will be made available if needed.

Results

A total of 40 patients of PD, 20 patients of PSP, 10 patients of MSA, 10 patients of vascular parkinsonism and 30 controls were recruited.

Clinical and Imaging Characteristics

PD (n = 40)

The duration of parkinsonism ranged between 1 and 8 years (Table 1). Asymmetric (97.5%) side and upper limb (92.5%) site onset of motor symptoms was most common presentation. Tremor‐dominant parkinsonism (75%) was the commonest subtype. Eight patients (20%) complained of hyposmia and three patients (7.5%) anosmia. Sixteen patients (40%) had INSIT score ≤4. Thirty‐six patients (90%) were on levodopa‐carbidopa (LCD), 21 (52.5%) on trihexyphenidyl, 10 (25%) on dopamine agonist, and four (10%) were drug naïve. The mean TLED was 422.6 ± 227.2 mg. The mean NMSS score was 45.5 ± 32.1.

TABLE 1.

Comparison of baseline disease characteristics among the groups

	PD (n = 40)	PSP (n = 20)	MSA (n = 10)	Vascular Parkinsonism (n = 10)	Control (n = 30)	P‐value
Gender (M: F)	28:12	19:1	9:1	9:1	15:15	‐
Age (years)	55.4 ± 10.1	61.4 ± 6.6	59.9 ± 4.6	60.9 ± 11.0	50.7 ± 10.7	0.09
Age range (years)	40–74	53–82	53–66	43–76	45–60	‐
Age of onset (years)	51.3 ± 10.3	60.0 ± 6.7	59.0 ± 5.1	57.2 ± 9.6	NA	0.23
Mean duration of parkinsonism (years)	4.2 ± 4.8	2.4 ± 1.3	2.5 ± 1.6	4.7 ± 5.9	NA	0.12
Mean INSIT score (range)	5.7 ± 2.5 (4–8)	6.2 ± 2.4 (4–8)	7.7 ± 1.0 (7–8)	6.3 ± 1.4 (4–8)	8.5 ± 0.8 (8–9)	0.16
Mean MOCA score (range)	26.4 ± 2.9 (24–29)	20.4 ± 4.0 (18–24)	27.5 ± 3.0 (24–30)	19.4 ± 6.3 (15–25)	28.2 ± 2.3 (26–30)	0.06
Mean UPDRS‐III score	25.2 ± 12.4	35.1 ± 17.5	30.1 ± 9.4	33.2 ± 8.2	‐	0.08

Abbreviations: INSIT, Indian smell identification test; MOCA, Montreal cognitive assessment; MSA, Multiple system atrophy; PSP, Progressive supranuclear palsy; PD, Parkinson's disease; UPDRS‐III, Unified Parkinson's disease rating scale.

^* P‐value <0.05.

PSP (n = 20)

The duration of parkinsonism ranged between 1 and 4 years. Rigidity (95%) and bradykinesia (90%) was the most common motor symptom of parkinsonism. Vertical supranuclear gaze palsy was seen in all patients and recurrent falls within 1 year in 15 patients (75%) and within 3 years of symptom onset in five patients (25%). Four patients (20%) complained of hyposmia and none of the patients complained of anosmia. Six patients (30%) had INSIT score ≤4. The mean total PSPRS score was 39.4 ± 15.2. Hummingbird sign on MRI was seen in six patients and the mean MRPI was 16.3 ± 3.2.

MSA (n = 10)

The duration of parkinsonism ranged between 1 and 5 years. All patients were MSA‐parkinsonian subtype with symmetrical rigidity and bradykinesia. Orthostatic hypotension was seen in eight patients (80%) and urinary disturbances in all patients (100%). Two patients (20%) complained of hyposmia and none of the patients complained of anosmia. Three patients (30%) had INSIT score ≤4. The mean UMSARS‐1, UMSARS‐II and UMSARS‐IV scores were 14.6 ± 4.8, 15.7 ± 8.8 and 1.5 ± 0.7 respectively. None of the patients had “hot cross bun sign” on MRI and two had putaminal rim sign.

Vascular Parkinsonism (n = 10)

The duration of parkinsonism ranged between 1 and 8 years. All patients had short‐stepped gait (100%) with lower limb rigidity and bradykinesia (100%). Freezing of gait was seen in six patients (60%), urinary incontinence in six patients (60%). None of the patients had hyposmia or anosmia. Two patients (20%) had INSIT score ≤4. Five patients had Fazekas grade 2, 2 had grade 1 and 3 had grade 3 vascular lesions on MRI.

Controls (n = 30)

The mean age of controls was 50.7 ± 10.7 (range: 45–60 years). There were 15 males (50%) and 15 females (50%). No patients complained of hyposmia or anosmia.

Olfactory Bulb Volume and Olfactory Sulcus Depth

Olfactory Bulb Volume

As compared to the PSP, MSA, vascular parkinsonism and control groups, the mean OBV was significantly lower in PD group (P = 0.003) on one‐way ANOVA (Fig. 1). This is summarized in Table 2. On post‐hoc analysis, there was significant difference in the total OBV between PD and controls (P < 0.001), PD and PSP (P = 0.02), PD and MSA (P = 0.02) and PD and vascular parkinsonism (P = 0.04). There was significant low total OBV in PD patients when compared with PSP (P = 0.004), MSA (P = 0.02), vascular parkinsonism (P = 0.03) and controls (P < 0.001) on student “t” test. There was no significant difference between right and left OBV within each group. The distribution of mean total OBV among the groups is shown in Fig. S2.

FIG. 1.

Coronal T2 MRI brain image showing olfactory bulb of control (red arrow) (A), Parkinson's disease patient (red arrow) (B); Coronal T2 MRI brain image showing olfactory bulb (red arrow) and olfactory sulcus (blue arrow) of progressive supranuclear palsy patient (C): Coronal T2 MRI brain image showing olfactory bulb of multiple system atrophy patient (red arrow) (D).

TABLE 2.

Comparison of olfactory bulb volume and olfactory sulcus depth among the groups using one‐way ANOVA

	PD (n = 40)	PSP (n = 20)	MSA (n = 10)	Vascular parkinsonism (n = 10)	Controls (n = 30)	P‐value
Right OBV (mm3)	54.0 ± 28.6	81.9 ± 36.5	75.7 ± 17.3	81.1 ± 43.7	94.3 ± 33.3	0.003*
Left OBV (mm3)	59.1 ± 39.2	82.8 ± 36.1	81.3 ± 26.3	79.5 ± 35.8	93.0 ± 35.2	0.02*
Total OBV (mm3)	113.3 ± 79.2	143.6 ± 71.2	141.3 ± 62.5	140.5 ± 86.5	187.4 ± 65.0	<0.001*
Right OSD (mm)	10.0 ± 1.7	11.0 ± 2.8	10.8 ± 2.1	10.5 ± 1.8	11.4 ± 1.3	0.12
Left OSD (mm)	10.0 ± 1.3	11.0 ± 2.5	10.6 ± 2.7	10.6 ± 1.3	11.7 ± 1.2	0.21
Total OSD (mm)	19.4 ± 8.1	20.8 ± 9.0	19.3 ± 8.1	19.4 ± 7.9	21.1 ± 2.2	0.41

Abbreviations: ANOVA, Analysis of variance; MSA, Multiple system atrophy; OBV, Olfactory bulb volume; OSD, Olfactory sulcus depth; PD, Parkinson's disease; PSP, Progressive supranuclear palsy.

^* P‐value <0.05; Values expressed as mean ± standard deviation.

Correlation of OBV in PD

There was no significant correlation between the total OBV and age at onset, duration of symptoms, TLED, UPDRS, NMSS. There was significant positive correlation between MOCA scores and total OBV (P < 0.001). This is summarized in Table 3.

TABLE 3.

Correlation of olfactory bulb volume and olfactory sulcus depth with disease characteristics in Parkinson's disease

	OBV		OSD
	R	P	r	P
Age at onset	−0.185	0.54	−0.141	0.14
Duration of illness	−0.057	0.61	−0.116	0.31
TLED	0.067	0.58	−0.047	0.70
UPDRS‐III	0.049	0.66	−0.018	0.87
NMSS	0.016	0.92	0.164	0.33
MOCA	0.435	0.001*	0.496	0.07
INSIT	0.028	0.12	0.112	0.26

Abbreviations: INSIT, Indian smell identification Test; MOCA, Montreal Cognitive Assessment; NMSS, Non‐motor symptoms scale; OBV, Olfactory bulb volume; OSD, Olfactory sulcus depth; TLED, Total levodopa equivalent dose; UPDRS‐III, Unified Parkinson's disease rating scale.

^* p‐value <0.05.

Olfactory Sulcus Depth

There was no significant difference in the mean OSD among the groups. This is summarized in Table 2.

Correlation of OSD in PD

There was no significant correlation between the total, right and left OSD and age at onset and duration of illness. There was no significant correlation between MOCA, TLED, UPDRS, NMSS scores and total OSD. This is summarized in Table 3.

Receiver Operating Characteristic Curve (ROC)

The area under the curve (AUC) was 0.803 which was significant (P < 0.001) (Fig. 2 ). The smaller the OBV, the more likely a diagnosis of PD can be made. From the curve coordinate, the cut off total OBV value of 107 mm³ had 77% sensitivity and 80% specificity in diagnosing a patient with PD. An OBV value less than 107 mm³ suggests a more likely diagnosis of PD.

FIG. 2.

Receiver operating characteristic curve (ROC) of total olfactory bulb volume in Parkinson's disease.

Discussion

The present study was aimed at determining the OBV and OSD using MRI in patients with PD, PSP, MSA, vascular parkinsonism and compare it with the controls. The OBV was significantly lower by 55% in PD patients as compared to the controls and by 30% as compared to atypical parkinsonian group. However, there was no difference in the OSD among the groups. OSD was evaluated in this study as it is easy to measure in axial and coronal planes by using standard MRI protocols as compared to the measurement of OBV. The measurement of OSD is an indirect marker to study OBV.

MRI‐based studies have shown reduced OBV in PD patients in comparison with controls. However, few studies have shown no significant difference in the OBV between PD and controls. Mueller et al (2005) studied OBV in 11 PD patients and nine controls. They used a 3‐dimensional CISS‐Sequence to visualize OB. The mean OBV in PD and in controls had no difference. ¹⁵ Altinayar et al from Turkey studied OBV in 41 PD patients and 19 age and gender matched healthy controls in 1.5‐T system. They did not find difference in the OBV in PD as compared to the controls but OBV of non‐tremor predominant PD patients were smaller as compared to the tremor‐dominant PD and controls. ¹⁶ Paschen et al from Germany studied OBV in 52 PD patients and 31 age‐matched controls using a 3.0 T MRI system. They used T2 weighted driven equilibrium gradient refocused sequence (DRIVE) in coronal slices through the OB. There was no difference in the OBV between PD and controls. ¹⁷

However, Wang et al from China studied OBV and OSD in 30 PD patients and 30 age‐ and sex‐matched healthy controls using Coronal T1‐weighted or T2‐weighted spin‐echo sequences in 3.0 T system and reported lower OBV and OSD in PD. ¹⁸ Similarly, Brodoehl et al from Germany found low OBV in PD patients. ² Tanik et al found reduced OBV and OSD in PD patients. They used the coronal T2‐weighted fast spin‐echo (FSE) sequences in 1.5‐T system. ¹⁹ Hang et al from China studied OBV and OSD in 100 PD patients and found only low OBV in PD as compared to controls with no significant difference in the OSD between the groups. ²⁰ We found low OBV in PD patients as compared to the controls but the OSD did not differ between the groups. Kim et al from South Korea studied OSD in 42 PD patients and eight controls and found no difference between the groups. ²¹ A systematic review and meta‐analysis on the published studies on OBV in PD published till 2015 was done by Li et al which included 216 PD patients and 175 healthy controls. They concluded that both the right and the left OBV were significantly smaller in PD patients than in healthy controls and the right OBV was remarkably larger than the left OBV in PD. ²² We found a significant positive correlation of MOCA score of PD patients with the total OBV indicating that decline in cognition was associated with reduced OBV. The main neurotransmitter in the OB is acetylcholine and there is functional acetylcholine deficiency in mild cognitive impairment and dementia. This may explain the association of reduced OBV with decline in cognition. Bohnen et al demonstrated that the cholinergic denervation of the limbic archicortex is a more robust determinant of hyposmia than nigrostriatal dopaminergic denervation in subjects with moderately severe PD. ²³ The positive correlation of MOCA and OBV suggests that OBV can be used as a radiological biomarker for cognitive impairment in PD patients as the disease progresses. Chen et al found significant negative correlation between the total OBV and disease duration only with no correlation with age, MOCA and UPDRS III scores. ²⁴ Hang et al found negative correlation between OBV and UPDRS III scores but not with the disease duration in PD. ²⁰ However, we did not find correlation of OBV in PD with age at onset, disease duration, TLED, motor parkinsonism severity score and non‐motor symptoms score. There was no correlation of OBV and INSIT score in PD suggesting that the OBV is not dependent on the normality of smell identification in PD.

Studies have demonstrated better olfactory function in PSP and MSA patients as compared to PD. Wenning et al studied olfactory function in 118 patients with PD, 29 with MSA, 15 with PSP, seven with corticobasal degeneration (CBD), and 123 healthy control subjects using the University of Pennsylvania 12 smell identification test (UPSIT) and reported mild impairment in MSA patients and normal olfaction in PSP and CBD patients. ²⁵ Doty et al found that the olfactory function of the PSP patients was markedly superior to that of the PD patients. ²⁶ Shill et al showed that the neuropathologically confirmed PSP patients had significantly better sense of smell than those with PD and hyposmia in PSP is related to the presence of additional Lewy body pathology. ²⁷ Katzenschlager et al reported higher UPSIT scores in patients with vascular parkinsonism in comparison with PD patients. ²⁸ The smell identification tests have shown impaired scores even in PSP, MSA and vascular parkinsonism as compared to PD and healthy controls. In our study, patients with PSP, MSA and vascular parkinsonism had lower INSIT scores. Due to variability in the smell identification test among different parkinsonian groups, an objective measure of OBV will aid in better discrimination among the parkinsonian disorders.

There are few studies which have compared the OBV of the PD patients with that of MSA, PSP and CBD. Chen et al studied volumes of the olfactory bulb, the olfactory tract, and olfaction‐associated cortical gray matter in 20 PD and 14 MSA patients. The OBV of PD patients (55.1 ± 10.7 mm³) was less than those of MSA patients (73.8 ± 9.1 mm³) or controls (75.9 ± 8.4 mm³). ²⁴ Sengoku et al from Japan studied olfactory bulbs and tracts (OB & T) in 13 patients with PD, 11 with MSA, five with PSP and five with CBD and found that the OB & T volume was smaller in PD than in MSA or PSP/CBD. ²⁹ We found low OBV in PD patients as compared to PSP, MSA and vascular parkinsonism but the OSD did not differ among the groups. These studies are summarized in Table S1.

Olfactory bulbs are the paired structures located at the base of the brain directly over the cribriform plate. According to the staging criteria of brain pathology in sporadic PD by Braak et al, the disease process commences in the OB, anterior olfactory nucleus and dorsal motor nucleus of the vagus and proceeds through the brainstem to involve SNpc in the midbrain. The early pathological involvement of the OB in PD is responsible for the frequent olfactory disturbance in PD which may precede the motor symptoms. Braak et al confirmed the presence of Lewy bodies in the mitral cells and tufted neurons of the OB. ³⁰ Apart from the OB, pathological changes have been demonstrated in the anterior olfactory nucleus, the piriform cortex, the amygdaloid complex, the entorhinal cortex, and the hippocampal formation in PD. Voxel‐based morphometry studies have shown that the olfactory dysfunction in PD is related to atrophy in olfactory‐eloquent regions of the limbic and paralimbic cortex. ¹⁸ Huisman et al found a significant increase (more than 100%) of tyrosine hydroxylase (TH)‐expressing cells in the OB of PD patients. The increase in the dopamine expression in the periglomerular cells of the OB suggests higher dopamine activity in OB which causes suppression of olfactory information, due to the inhibitory effect of dopamine on the transmission between olfactory receptor cells and mitral cells within the olfactory glomeruli. This explains the non‐reversibility of anosmia in PD with levodopa supplementation. ³¹ Kovacs et al reported the presence of glial cytoplasmic inclusions (GCIs) in all the OBs from MSA cases and suggested these pathological changes might be responsible for the olfactory dysfunction seen in MSA. MSA patients from our cohort had reduced OBV as compared to the controls but significantly higher as compared to PD patients. ³²

The OBV was low in PD in our study despite 60% of PD patients being normosmic suggesting that the OBV is not related to the olfactory function in PD. However, other studies have shown correlation of OBV with olfactory identification in PD suggesting that OBV is dependent on the olfactory function. ¹⁸ , ²⁰ Hummel et al reported no specific changes in the nasal mucosa/olfactory epithelium of seven hyposmic PD patients as compared to hyposmic controls suggesting that the olfactory loss in PD is not due to the damage to the olfactory epithelium. ³ Reduced OBV in PD in the present study may be due to central nervous pathology than the disrupted input to OB from the olfactory epithelium. We found relatively larger OBV in our study as compared to other studies (Table S1) which may be due to different ethnicity, brain size, estimation in 3 T MRI.

The strength of the study was the OBV and OSD was measured and analyzed across all the spectrum of atypical parkinsonism (MSA, PSP) and vascular parkinsonism, inclusion of patients from a different geographic region which has not been studied so far and the analysis of OBV, OSD in 3‐T MRI system. The limitation of the study was the relatively low sample size, confounding factor of Coronavirus disease 2019 induced olfactory dysfunction and lack of assessment of olfactory threshold and discrimination.

Conclusion

Olfactory bulb volume is reduced in patients with PD as compared to PSP, MSA, vascular parkinsonism and controls. OBV in PD was not associated with age at onset, disease duration, motor and non‐motor severity, INSIT score and dopaminergic drugs dosage except positive correlation with cognitive status. A total OBV value less than 107 mm³ in a patient with parkinsonism suggest a diagnosis of PD. OBV estimation adds to the armamentarium in the diagnosis of PD.

Author Roles

(1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the first draft, B. Review and Critique.

D.D.: 1B, 1C, 2A, 2B, 3A

K.K.: 1B, 1C, 2B, 2C, 3B

V.V.H.: 1A, 2C, 3B

N.K.: 1A, 2C, 3B

R.Y.: 1A, 2B, 3B

P.K.P.: 1A, 1C, 2C, 3B

R.R.M.: 1A, 1B, 1C, 2A, 2B, 3B

Disclosures

Ethical Compliance Statement: Institute Ethics Committee approval was obtained (NO. NIMH/DO/IEC‐BS& NS DIV/2020/29‐04‐2020). and the informed consent was obtained from the patients. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.

Funding Sources and Conflicts of Interest: No specific funding was received for this work and there are no conflicts of interest relevant to this work.

Financial Disclosures for the Previous 12 Months: There are no financial disclosures to report.

Supporting information

Figure S1. Measurement of OB volume (OBV) using 3D Slicer software.

Figure S2. The distribution of mean total OB volume (OBV) among the groups.

TABLE S1. Summary of the studies on olfactory bulb volume and olfactory sulcus depth in Parkinson's disease