|Year : 2020 | Volume
| Issue : 3 | Page : 163-166
Unawareness of hyposmia in patients with idiopathic Parkinson’s disease
Utkarsh Patel, Charulata Savant Sankhla
Department of Neurology, P D Hinduja National Hospital, Mumbai, Maharashtra, India
|Date of Submission||09-May-2020|
|Date of Decision||31-May-2020|
|Date of Acceptance||25-Aug-2020|
|Date of Web Publication||07-Nov-2020|
Dr. Charulata Savant Sankhla
Department of Neurology, P D Hinduja National Hospital and Medical Research Center, Mumbai, Maharashtra.
Source of Support: None, Conflict of Interest: None
BACKGROUND: Loss of olfaction is a hallmark of neurodegenerative disorders such as idiopathic Parkinson’s disease (PD) and it may precede the clinical syndrome of PD by many years. Olfactory bulb is probably the earliest site of pathology in PD. This study examines the frequency of unawareness of hyposmia in study cohorts with and without PD and its correlation with cognitive impairment. The objective of this study was to assess olfactory function using the Indian Smell Identification Test (INSIT), which evaluates the unawareness of hyposmia in patients with idiopathic PD. MATERIALS AND METHODS: Olfaction was assessed in 30 PD patients and 30 healthy controls by using INSIT. During this test, the subjects were asked to identify smell from a set of choices and were scored out of 10. The cutoff used for hyposmia was an INSIT score of ≤4. Unawareness was defined as reporting a normal sense of smell in the setting of a low INSIT. Cognitive status was assessed by using Mini Mental State Examination (MMSE) to study the effect of cognitive status on unawareness of hyposmia in PD cases. RESULTS: The mean age for the PD and control groups was 64.3± 10.6 years and 63.9 ± 10.2 years, respectively. Most of the participants were males: 53% and 56% in the PD and control groups, respectively. Out of the 30 patients in each group, 18 patients were unaware of hyposmia in the PD group as compared with 4 patients in the control group. The mean smell identification score using INSIT was 4.13 ± 2.42 in the PD group and 6.86 ± 2.3 in the control group, which was found to be significant with a p value of <0.0001. In the PD group, the mean MMSE score in subjects who were unaware of hyposmia was 27.89, whereas the mean MMSE score in subjects who were aware of smell was 29.25. This was found to be not statistically significant with a p value of 0.1087. CONCLUSION: Unawareness of hyposmia in patients with PD is high as compared with that in the elderly without PD. Under-reporting of hyposmia is seen in patients with PD. There is no increase in the unawareness of hyposmia in patients with PD who exhibit dementia. All these lead to a premise whereby population screening using INSIT could be used for the early detection of PD in those who already harbor the earliest pathology of neurodegeneration.
Keywords: Hyposmia, Indian smell identification test, Parkinson’s disease
|How to cite this article:|
Patel U, Savant Sankhla C. Unawareness of hyposmia in patients with idiopathic Parkinson’s disease. Ann Mov Disord 2020;3:163-6
|How to cite this URL:|
Patel U, Savant Sankhla C. Unawareness of hyposmia in patients with idiopathic Parkinson’s disease. Ann Mov Disord [serial online] 2020 [cited 2021 Feb 25];3:163-6. Available from: https://www.aomd.in/text.asp?2020/3/3/163/300258
| Introduction|| |
Parkinson’s disease (PD) is predominantly a motor disorder; however, nonmotor symptoms (NMS) are often an integral part of this disease. The spectrum of NMS includes mood disorders, dementia, sleep disorders, impulse-control disorders, psychosis, and autonomic dysfunctions. These are major determinants of the quality of life in patients with PD.
Some of the NMS, such as hyposmia, depression, and anxiety, can precede the onset of Parkinsonism More Details. Hyposmia, identified as a reduced sensitivity to odor, is a common nonmotor symptom of PD that antedates the typical motor symptoms by several years. It occurs in ∼90% of early-stage cases of PD. It is also well established that hyposmia may predate the clinical syndrome of PD. It is now accepted that olfactory bulb is probably the earliest site of pathology in PD.
Cognitive impairment occurs many years before the onset of motor symptoms. All these lead to a premise whereby hyposmia may serve as a screening tool for the early detection of PD in those who already harbor the earliest pathology of neurodegeneration. However, in India, very few studies that test olfaction in patients with PD have been undertaken.
- (1) To evaluate the olfactory impairment in patients with PD by using a 12-odorant Indian Smell Identification Test (INSIT).
- (2) To evaluate the unawareness of hyposmia among PD patients and controls and its correlation with cognitive impairment.
| Materials and Methods|| |
The present study was carried out at P. D. Hinduja National Hospital and Research Centre, Mahim, Mumbai. All subjects signed a written informed consent form that was approved by the Institutional Review Board.
For the present analysis, 30 consecutive patients with PD who did not report hyposmia, irrespective of age, sex, and duration of or stage of disease, and 30 healthy controls who did not have hyposmia historically were included in the study.
Patients with PD were diagnosed on the basis of UK Parkinson’s Disease (UKPDS) Brain Bank Clinical Diagnostic Criteria.
Idiopathic PD patients with
- a) History or evidence of head trauma,
- b) Intracranial malignancy,
- c) Local nasal pathology (i.e. nasal polyps, deviated nasal septum, atrophic rhinitis),
- d) Chronic sinusitis,
- e) Smoking,
- f) Upper respiratory tract infections (within 1 week),
- g) Exposure to drugs that may alter olfaction,
- h) Dementia and psychosis.
There were two groups. One group had 30 patients with PD, and the other group had 30 age- and sex-matched healthy individuals (controls). Date of PD onset was derived from interviews/examinations of subjects and caregivers and/or reviews of medical records. All subjects were asked before testing whether their sense of smell was normal, reduced, or absent. Only patients who reported a normal sense of smell were included in both the groups.
All subjects completed the Indian Smell Identification Test (INSIT). Essences of 12 commonly used items were used as odorants. The odorants were chosen to represent the familiarity in day-to-day life. The essence of cardamom, kewra, khus, lemon, mango, orange, pineapple, rose, thinner, vanilla, rose, and banana in commercially available 20ml airtight bottles was used. Cotton buds dipped in the essence were used as a test material, and they were placed at a distance of 1cm in front of one of the nostrils with the other nostril closed; this process was repeated in the other nostril. The subjects were asked to sniff and identify the smell from the answer card containing four choices for each odorant. The first response was taken: 1 was the score for the correct response, and 0 was the score for the wrong response.
For the INSIT, the maximum score is 10. The cutoff used for hyposmia was an INSIT score ≤4. Lack of awareness was defined as reporting a normal sense of smell in the setting of a low INSIT. Student’s t test was used to compare the mean INSIT scores in the patient and control groups.
The cognitive status was assessed by using Mini Mental State Examination (MMSE). All 30 patients in the PD group underwent MMSE assessment (the P value cutoff for a statistically significant difference was <0.05).
| Results|| |
Thirty PD patients and 30 controls were included in the present study. The mean age for the PD and control group was 64.3 ± 10.6 years and 63.9 ± 10.2 years, respectively. Most of the participants were males: 53% and 56% in the PD and control group, respectively. The mean smell identification score using INSIT was 4.13 ± 2.42 in patients and 6.86 ± 2.3 in the control group, which was found to be significant with a P value of <0.0001.
Out of the 30 patients in the PD group, 18 patients (60%) had an INSIT score of <4 [Table 1]. Out of the 30 patients in the control group, 4 patients (13%) had an INSIT score of <4 [Table 1]. This means that 18 patients were unaware of hyposmia in the PD group as compared with 4 patients in the control group, which was found to be statistically significant with a P value of <0.001. Details of the baseline characteristics of patients with PD and controls are given in [Table 2].
The maximum specificity and sensitivity for INSIT was obtained when a cutoff value of 4 was used, that is, values ≤4 indicated disease. Using this cutoff value, we obtained a sensitivity of 60% and a specificity of 86% in our study [Figure 1].
|Figure 1: Percentage of correct responses for each item in Indian Smell Identification Test (INSIT)|
Click here to view
The mean MMSE score in subjects who were unaware of hyposmia was 27.89 ± 1.1. The mean MMSE score in subjects who were aware of hyposmia was 29.25 ± 0.29. These scores were not statistically significant with a P value of 0.1087 (the P value cutoff for statistically significant difference was <0.05).
| Discussion|| |
The importance of olfaction is often underestimated in clinical practice. Braak et al. depicted that olfactory neuronal loss (anterior olfactory nucleus) takes place much earlier in the course of the illness even before the various motor areas get involved. In PD, spread from the olfactory bulb moves sequentially to the brainstem and does not affect the limbic and cortical areas until later stages. These findings indicate that the olfactory dysfunction occurs much earlier in the course of the disease and stays unaltered with disease progression.
In the current study, unawareness of olfaction loss was significant in PD patients as compared with controls. This unawareness of a loss of smell indicates that a formal smell test is essential to be used as a screening tool for early detection of PD. The smell identification ability of Indian PD patients was assessed by using a new olfactory test, INSIT. With INSIT, significant differences in scores were seen (P < 0.001) among the PD and control groups. This clearly shows that olfaction is impaired in PD. Using INSIT, in the control group, the percentage of correct identification ranged from 100% (coffee) to 10% (banana), whereas in the PD group, it ranged from 63% (coffee) to 10% (rose).
The maximum specificity and sensitivity for INSIT was obtained when a cutoff value of 4 was used, that is values ≤4 indicated disease. Using this cutoff value, we obtained a sensitivity of 60% and a specificity of 86% in our study. Using a cutoff value of 4, Behari et al. obtained a sensitivity of 79.2% and a specificity of 78% in their study.
Deeb et al. found that a basic smell test is as effective as the Dopamine Transporter Scan (DaTSCAN) in the diagnosis of PD. They reported that the sensitivity of The University of Pennsylvania Smell Identification Test (UPSIT) (86%) was not very different from that of the DaTSCAN (92%). This shows that a good olfactory test could become a keystone in the early diagnosis of PD. Using a 33-item olfactory multiple-choice test (Italian Olfactory Identification Test; IOIT), Maremmani et al. observed a sensitivity of 93% and a specificity of 99% in healthy Italian subjects and PD patients; using a hyposmia rating scale, Millar et al. observed a sensitivity of 70% (60.81%) and a specificity of 85% (65.100%) in their population. An improvement in the sensitivity and specificity of INSIT with appropriate modifications can be made possible with further studies.
Mao et al. performed a study to identify olfactory dysfunction and investigate the relationship between hyposmia and cognitive function in 63 patients with PD in the People’s Republic of China. They found that the incidence of hyposmia measured by each kind of odor in patients with PD was statistically higher than in controls. The receiver operating characteristic analysis revealed that rose petal odor (with a sensitivity of 87.3% and a specificity of 87.5%) and isovaleric acid (with a sensitivity of 83.3% and a specificity of 93.7%) were more superior for recognizing odor-identification impairment in patients with PD than other odors, which corroborates with the findings in our study. The Chinese version of the Montreal Cognitive Assessment (MoCA) was applied to assess the subjects’ olfactory and cognitive functions in their study. Their analysis showed that impaired visuospatial and executive function was associated with hyposmia.
Olfactory dysfunction is reported in other neurological diseases as well. Hence, it becomes difficult to obtain a high specificity for PD by using the olfactory test alone. The ability of INSIT to differentiate between PD and other Parkinsonism syndromes was not assessed in this study. Wenning et al. reported severely impaired olfaction in patients with PD, whereas patients with atypical Parkinsonism such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), or corticobasal degeneration (CBD) have either preserved or only mildly impaired olfaction. Therefore, it is of utmost importance to have further studies to test olfaction in other neurological diseases apart from PD by using INSIT.
In the PD group, unawareness of hyposmia was not associated with cognitive impairment. In the elderly without Parkinsonism, unawareness of hyposmia is common and correlates with the presence of cognitive impairment, which is weighted toward language and verbal memory problems typical of AD. It is worth speculating that these differences reflect the neuropathological underpinnings in both PD and AD.
In the present study, only odor identification was evaluated. As different components contribute differently to olfaction loss, the inclusion of other components of olfaction (such as odor discrimination and odor threshold) in the smell test will provide a more sensitive and specific way of evaluating olfaction in patients with PD, which will help in enhancing its discriminative value.
As already mentioned, further studies are required to determine the clinical utility of the INSIT and its ability to differentiate PD from other neurodegenerative disorders, decay of the odorant over time, and modify it if necessary. Unawareness of a loss of smell may also be an early indicator of cognition decline. Further prospective studies that apply a series of neuropsychological tests such as Montreal Cognitive Assessment (MoCA) or Addenbrooke’s Cognitive Examination (ACE III) in large samples in multicentric studies are needed to confirm our findings and to investigate the relationship between unawareness of hyposmia and cognitive status in patients with PD. Follow-up of these patients may allow us to understand whether this may be a marker for future PD dementia.
Acknowledgment is due to Professor Madhuri Behari for INSIT kit and PD nurse Alita Jacinto.
Utkarsh Patel contributed toward writing the first draft and its revision. Charulata Savant Sankhla contributed toward a revision of the first draft.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]