Quantitative Evaluation of Olfactory Function in Spinocerebellar Ataxia Type3 and Type1 in China: A Clinical Study

Quantitative Evaluation of Olfactory Function in Spinocerebellar Ataxia Type3 and Type1 in China: A Clinical Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Quantitative Evaluation of Olfactory Function in Spinocerebellar Ataxia Type3 and Type1 in China: A Clinical Study Yiwen Liu, Tong Wu, Hao Zhou, Kepu Chen, Yongsheng Han This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4661059/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 12 You are reading this latest preprint version Abstract Objectives: This study investigates olfactory function and clinical characteristics in spinocerebellar ataxia (SCA) patients, exploring the link between motor and nonmotor symptoms. Methods: In a study conducted at the Neurology Institute Affiliated Hospital of Anhui University of Chinese Medicine, 30 spinocerebellar ataxia (SCA) patients diagnosed from August 2020 to August 2023 were matched with 30 controls. Olfactory functions were evaluated using the Institute of Psychology's olfactory test. The SCA group's ataxia severity was assessed with the International Cooperative Ataxia Rating Scale (ICARS). Variations in Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Pittsburgh Sleep Quality Index (PSQI) scores were compared between groups, and correlations between olfactory function and SCA symptoms were examined. Results: In the SCA group, olfactory scores were significantly lower compared to controls ( P < 0.001). SCA patients had higher HAMA ( P = 0.005), HAMD ( P = 0.02), and PSQI ( P < 0.001) scores. However, Olfactory identification correlated negatively with age (r = −0.377, P = 0.041) in SCA patients. No significant correlations were found between olfactory function and disease duration, ICARS, HAMA, HAMD, or PSQI scores in the SCA group. Conclusion: The olfactory dysfunction is prevalent in SCA patients, But there was no significant correlation between motor symptoms and non-motor symptoms. Spinocerebellar ataxia Olfactory function Olfactory test Ataxia Nonmotor symptoms INTRODUCTION Spinocerebellar ataxias (SCAs) are a group of autosomal dominant inherited neurodegenerative diseases characterized by progressive ataxia, which can cause severe disability and premature death [1]. Although the motor symptoms of this disease, such as ataxia, have received widespread attention from neurologists, nonmotor symptoms, including olfactory impairment, sleep disturbances, anxiety, and depressive symptoms, have often been overlooked. The pathophysiological mechanisms of olfactory dysfunction in SCA remain unclear, and limited clinical research exists on olfactory function in SCA. Additionally, limited studies have assessed the relationship among olfactory function, severity of ataxia, and nonmotor symptoms in SCA. Therefore, this study aimed to explore the correlation between olfactory impairment and other clinical symptoms to improve our understanding of olfactory dysfunction in patients with SCA. We included 30 patients with SCA who visited the Neurology Institute Affiliated Hospital of Anhui University of Chinese Medicine over the past 3 years as research participants. MATERIALS AND METHODS Inclusion Criteria (1) Patients diagnosed with SCA through genetic testing; (2) Absence of rhinitis or common cold symptoms; and (3) Absence of severe cognitive impairment and psychiatric symptoms. Exclusion Criteria (1) Patients with cold, rhinitis, nasal polyps, or other lesions that may affect olfactory function and (2) History of head trauma, alcohol abuse, smoking, or drug abuse. Clinical Data Considering the aforementioned inclusion and exclusion criteria, we included 30 patients diagnosed with SCA who visited the Neurology Institute Affiliated Hospital of Anhui University of Chinese Medicine between August 2020 and August 2023. Among them, 18 were men and 12 were women, with an age range of 16–71 (42.00 ± 15.68) years. Additionally, 30 healthy controls were selected based on the exclusion criteria, matched for handedness, gender, age, and years of education with the patient group. Among the controls, 20 were men and 10 were women, with an age range of 18–71 (42.25 ± 15.31) years. Neurological function assessment The neurology specialist, who received formal training, conducted the following tests before treatment: (1) International Cooperative Ataxia Rating Scale (ICARS): This test evaluated the severity of motor symptoms, including posture and gait disturbances, dynamic function, speech disorders, and eye movement in the SCA group. (2) Hamilton Anxiety Rating Scale (HAMA): This test assessed the level of anxiety in the SCA and control groups. (3) Hamilton Depression Rating Scale (HAMD): This test evaluated the depressive state of the SCA and control groups. (4) Pittsburgh Sleep Quality Index (PSQI): This test assessed the sleep quality of the SCA and control groups. Olfactory Function Assessment This evaluation was conducted using the odor detection test developed by the Institute of Psychology, Chinese Academy of Sciences, which comprises three parts: (1) Olfactory Threshold Test: It comprises 20 odorant sticks numbered 1–20 and 4 baseline sticks numbered 0. The odorant sticks presented the same odor with decreasing concentrations as the number increased, thereby forming a concentration gradient. The baseline sticks presented a baseline odor as the blank control. The threshold was determined by counting the number of odorant sticks where the odor was correctly identified by the participant with a 50% probability. During each trial, participants were blindfolded, and the odorant and baseline sticks were randomly presented in a sequence. Participants were asked to identify the stick that presented a stronger odor, allowing the evaluation of their ability to detect differences in odor concentration. The threshold was calculated using fitting software based on repeated tests, with a total score of 20 points. (2) Olfactory Discrimination Test: This test comprised 16 sets of sticks numbered 1–16, with each set containing 3 sticks, and thus, totaling 48 sticks. Each set contained two sticks presenting the same odor and one stick presenting a different odor. During each trial, the participants were blindfolded, and they were presented with three sticks in a random order. The participants were asked to identify the stick with a different odor from the other two, indicating their ability to distinguish between different odor characteristics. Each correct answer scored 1 point, with a total score of 16 points. (3) Olfactory Identification Test: This test comprised 16 sticks numbered 1–16, with each stick presenting a unique odor. The odors used were familiar to the Chinese population to avoid cultural differences and personal experience biases. During each trial, the participants were presented with one stick and provided four options to select the name of the odor. Each correct answer scored 1 point, with a total score of 16 points. The olfactory tests were conducted in an environment with effective air circulation and lacking other odors. The participants were not allowed to use perfume on the day of the test, and they refrained from consuming food and drinks 30 min before the test. All sticks were presented as felt-tip pens, with the tip placed approximately 1 cm in front of the nose. Each stick was shaken 5–7 times, with the shaking range not exceeding the width of the nostrils. The total score of the olfactory test ranged from 0 to 52, with higher scores indicating better olfactory function. Statistical Analysis The data analysis was conducted using SPSS version 25. For normally distributed continuous data, results were presented as mean ± standard deviation (x ± s), and between-group comparisons were performed using the independent samples t-test. For non-normally distributed continuous data, the results were presented as median and interquartile range [M (P25, P75)], and between-group comparisons were conducted using Wilcoxon’s rank-sum test. The Pearson correlation (for normally distributed data) and Spearman’s rank correlation analyses (for non-normally distributed data) were used to determine the correlation between olfactory function and clinical characteristics of patients with SCA. The differences were considered statistically significant at P ≤ 0.05. RESULTS No statistically significant differences in gender, age, and education level were observed between the SCA and the control groups. The olfactory threshold, discrimination, identification, and total olfactory function scores were lower in the SCA group compared with the control group ( P < 0.001). Additionally, HAMA ( P = 0.009), HAMD ( P = 0.018), and PSQI ( P < 0.001) scores were higher in the SCA group compared with the control group (Table 1 ). The total olfactory identification score in the SCA group was negatively correlated with age (r = − 0.401, P = 0.022). No correlation between olfactory function and disease duration, ICARS, HAMA, HAMD, or PSQI scores was observed in the SCA group (Table 2 ). Table 1 Clinical Data of the SCA and Control Groups Observation Index SCA Group Control Group P Value Gender (M/F) 15/15 20/10 1 Age (years) 42.73 ± 13.99 44.63 ± 15.91 0.615 Disease Duration (years) 6.00 ± 3.31 - - Olfactory Threshold (20 points) 9.90 ± 4.26 13.78 ± 3.69 0.000* Olfactory Discrimination (16 points) 8.27 ± 2.52 12.25 ± 3.52 0.000* Olfactory Identification (16 points) 9.87 ± 2.60 14.36 ± 4.19 0.001* Olfactory Total Score 28.03 ± 5.27 42.43 ± 5.35 0.000* ICARS Score 31.20 ± 6.56 - - HAMA 16.03 ± 4.13 1.35,5 0.005* HAMD 9.10 ± 4.72 2.3,6 0.027* PSQI 7.56 ± 4.16 1.25,3 0.000* *Statistically significant at r ≤ 0.05. Table 2 Correlation between Olfactory Function and Motor and Nonmotor Symptoms in the SCA Group Variable Olfactory Threshold Olfactory Discrimination Olfactory Identification Olfactory Total Score r P r P r P r P Age -0. 139 0.238 -0.276 0. 135 -0.377 0.041* -0.420 0.027* Disease Duration -0.251 0.359 -0.212 0 259 -0.15 0.414 -0.221 0.238 ICARS score 0.085 0.582 -0.314 0.11 -0.028 0.882 -0.039 0.707 HAMA -0.052 0.712 -0.093 0.612 -0.319 0. 221 -0. 199 0.366 HAMD -0.075 0.67 -0 115 0.55 -0.20 0.357 -0.203 0.508 PSQI -0. 213 0.35 0.053 0.692 -0. 263 0.402 -0.136 0.711 *Statistically significant at r ≤ 0.05. DISCUSSION Olfactory dysfunction is commonly observed in various neurodegenerative diseases, and our clinical observations indicate that patients with SCA exhibit olfactory impairment to a certain extent. Several studies have highlighted the close relationship between the cerebellum and olfactory function. Ivanka Savic et al. [1] used functional magnetic resonance imaging (fMRI) to reveal the activation of the cerebellum during olfactory stimulation. Juan Fernandez-Ruiz et al. [2] were the first to confirm olfactory dysfunction in patients with cerebellar damage. However, notably, the degree of olfactory impairment in patients with SCA is not as severe as those with Parkinson’s disease (PD) or Alzheimer’s disease (AD). Furthermore, studies have revealed a close relationship between olfaction and cognitive function in patients with SCA. Vázquez-Pérez et al. [3] investigated olfactory function in 53 patients with SCA2 and 53 healthy controls and revealed significantly lower olfactory scores in the SCA2 group compared with the healthy control group. Moreover, a significant correlation was observed between the olfactory scores and Mini-Mental State Examination (MMSE) scores (p = 0.03). In this study, we evaluated the olfactory function of 30 patients with SCA (primarily SCA1 and SCA3 subtypes) and analyzed its correlation with motor impairment, anxiety and depression status, and sleep quality. The results of this study suggest that, compared with the control group, patients in the SCA group exhibit decreased olfactory threshold, discrimination, and identification, consistent with the findings from previous studies. Galvez et al. [4] demonstrated that olfactory discrimination and identification abilities were significantly impaired in patients with SCA7 while their olfactory threshold remained within normal levels, suggesting that neurological damage in patients with SCA7 affects olfaction but preserves olfactory perception ability. Similarly, Braga-Neto et al. [5] found a significant decrease in the olfactory ability of patients having SCA3, with the degree of olfactory dysfunction correlating with patient age, education level, smoking status, and MMSE scores. Additionally, significant differences in olfactory function have been observed among different subtypes of SCA. Mariana Moscovich et al. [6] conducted olfactory tests on patients with SCA10 and SCA2, and the results indicated olfactory impairments in patients with SCA2 but no significant olfactory defects in patients with SCA10 [7]. The mechanism underlying olfactory dysfunction remains unclear, but the decrease in olfactory threshold is typically associated with damage to the olfactory epithelium and olfactory sensory neurons [8]. This damage is most commonly attributed to chronic rhinitis [8]. Therefore, it is crucial that studies evaluating olfaction in patients with SCA exclude the influence of peripheral olfactory system damage. Numerous studies have found olfactory dysfunction in various neurological disorders, including idiopathic PD [9, 10], AD, schizophrenia, and multiple sclerosis (MS). Olfaction and movement disorders share a close relationship, with olfactory dysfunction serving as an early indicator for the onset of certain diseases. In PD, the prevalence of olfactory loss exceeds that of tremor. In patients with MS, olfactory dysfunction is significantly negatively correlated with the number of active lesions in the primary and secondary olfactory cortices [11, 12]. Traditionally, the human cerebellum is the center for motor coordination; it contains more neurons than other parts of the brain and is structurally connected to all major branches of the central nervous system, including the cerebrum, basal ganglia, diencephalon, limbic system, brainstem, and the spinal cord [11, 12]. The cerebellum also plays a role in olfactory function [13], and the evidence supporting its involvement in olfactory processing includes the following: (A) reports of olfactory defects in patients with cerebellar or near-cerebellar tumors [14, 15]; (B) signs of cerebellar abnormalities in patients with olfactory loss-related disorders, such as schizophrenia [16]; and (C) fMRI demonstrating cerebellar activation during olfactory processes [2]. fMRI studies revealed activation in the posterior lateral hemisphere of the cerebellum following odor induction, activation of the uvula and posterior quadrangular lobes following odor recognition tasks, and activation of the right central lobule and vermis solely evoked through olfaction [17]. (D) T Connelly et al. conducted the University of Pennsylvania Smell Identification Test on patients with ataxia, primarily caused by cerebellar pathology (SCA and related disorders) and Friedrich’s ataxia (a condition primarily associated with loss of input cerebellar pathways). The results showed that olfactory test scores were significantly lower in patients with cerebellar disease compared with the control group [18]. The olfactory dysfunction in SCA may be related to disruptions in brain network function associated with olfaction. fMRI conducted on the central olfactory system revealed that patients with PD who possess olfactory dysfunction exhibit a significant decrease in regional homogeneity in traditional olfactory regions, such as the amygdala, olfactory gyrus, orbitofrontal gyrus, parahippocampal gyrus, and insula, and few nontraditional olfactory centers, such as the prefrontal gyrus and temporal pole, suggesting that besides traditional olfactory core regions, other brain regions also participate in olfaction [19]. For example, the decrease in olfactory threshold is correlated with the left primary olfactory cortex [20]; odor discrimination tasks are associated with the frontal and temporal lobes and the limbic system such as the orbitofrontal cortex and hippocampus [21]; odor recognition tasks activate the cerebellum, temporal lobe, and parietal lobe cortex [22]; and the cerebellum receives olfactory inputs from the piriform cortex via the ventral striatum [23]. The basal ganglia, as a core component of the neural circuitry hypothesis, can receive signal inputs from the primary olfactory cortex, including the olfactory tubercle, during olfactory tasks [24], and patients with PD having olfactory dysfunction exhibit a significant decrease in dopamine transporter uptake in the bilateral caudate nucleus and the left anterior and posterior putamen [25]. In this study, the age of the patients with SCA was negatively correlated with various olfactory scores, indicating that age is an important risk factor for olfactory dysfunction [26]. The HAMA, HAMD, and PSQI scores were higher in the SCA group than the control group, suggesting that most patients with SCA have anxiety, depression, and sleep disorders. However, no correlations between the scores of HAMA, HAMD, and PSQI and olfactory function were observed in the SCA group in this study. The olfactory sticks used in this study were developed by the Institute of Psychology, Chinese Academy of Sciences. The sticks offer the advantages of convenience, accuracy, and high sensitivity. The selected odors are familiar to the Chinese population; nonirritable; and enable the assessment of the sensitivity level of odor detection and odor perception and the ability to perceive odor characteristics to determine their association with odor concepts in the memory system. These sticks meet the requirements for scientific research and clinical examinations. In conclusion, this study demonstrates a high prevalence of olfactory dysfunction in patients with SCA, characterized by a comprehensive decrease in olfactory threshold, discrimination, and identification functions. No correlation is observed between olfactory dysfunction in SCA and motor symptoms, pain, anxiety, depression, or sleep disturbances. However, this study has certain limitations. First, the sample size was relatively small, which may lead to biased results. Second, fMRI examinations were not conducted to further explore the neurobiological mechanisms underlying olfactory dysfunction in SCA. Lastly, no follow-up investigation was conducted to determine the relationship between olfactory dysfunction and treatment outcomes. Declarations Ethics Approval: This study has been approved by the Ethics Committee of Affiliated Hospital, Institute of Neurology, Anhui University of Chinese Medicine under approval number 2020 Lunzi (21). The approval was granted on November 01, 2020. The research conducted in this study adheres to the ethical guidelines set forth by the Ethics Committee of Affiliated Hospital, Institute of Neurology, Anhui University of Chinese Medicine . Consent to Participate: All participants involved in this study provided informed consent prior to their participation. They were informed about the study's purpose, procedures, potential risks, and benefits. Participants were assured of their voluntary participation and their right to withdraw from the study at any time without consequences. Confidentiality: Participants' confidentiality and anonymity have been strictly maintained throughout the study. Any personal information collected has been kept confidential and will only be used for research purposes. Data will be reported in aggregate form to ensure individual privacy. Contact Information: For any questions regarding ethics approval, consent procedures, or participant rights, please contact: [corresponding author:Yongsheng Han] [Affiliated Hospital, Institute of Neurology, Anhui University of Traditional Chinese Medicine] [Email Address: [email protected] ] [Phone Number:13866159323]； Competing interests The authors declare no Competing interests. Funding This study was supported by National Natural Science Foundation of China (8177425); Natural Science Foundation of Anhui Province (1808085MH245); and Key Research and Development Program of Anhui Province (S202004a07020061). Ethics approval and Informed consent statement This study has been approved by the Ethics Board of Anhui University of Chinese Medicine. Written informed consent was obtained from the patient to participate. Consent for publication Written informed consent for publication of the clinical details was obtained from the patient. Data availability The datasets generated during and/or analyzed during the current study are not publicly available, but are available from the corresponding author on reasonable request. Authors ’ contributions Conceptualization: Yongsheng Han; Writing—original draft: Yiwen Liu and Hao Zhou; Writing—review and editing: Tong Wu and Kepu Chen. Approval of final manuscript: all authors. Availability of data and materials Relevant information is available from the corresponding author. Acknowledgements We would like to express our sincere gratitude to all individuals and organizations who contributed to the completion of this study. Their support and assistance were invaluable in the research process. References Savic I. Brain imaging studies of the functional organization of human olfaction. Chem Senses . 2005;30(Suppl 1):i222-223. https://doi.org/10.1093/chemse/bjh194. Fernandez-Ruiz J, Díaz R, Hall-Haro C, et al. Olfactory dysfunction in hereditary ataxia and basal ganglia disorders. Neuroreport . 2003;14(10):1339-1341. https://doi.org/10.1097/01.wnr.0000077551.91466.d3. Velázquez-Pérez L, Fernandez-Ruiz J, Díaz R, et al. Spinocerebellar ataxia type 2 olfactory impairment shows a pattern similar to other major neurodegenerative diseases. J Neurol . 2006;253(9):1165-1169. https://doi.org/10.1007/s00415-006-0183-2. Galvez V, Diaz R, Hernandez-Castillo CR, et al. Olfactory performance in spinocerebellar ataxia type 7 patients. Parkinsonism Relat Disord . 2014;20(5):499-502. https://doi.org/10.1016/j.parkreldis.2014.01.024. Braga-Neto P, Felicio AC, Pedroso JL, et al. Clinical correlates of olfactory dysfunction in spinocerebellar ataxia type 3. Parkinsonism Relat Disord . 2011;17(5):353-356. https://doi.org/10.1016/j.parkreldis.2011.02.004. Moscovich M, Munhoz RP, Moro A, et al. Olfactory Function in SCA10. Cerebellum . 2019;18(1):85-90. https://doi.org/10.1007/s12311-018-0954-1. Moscovich M, Munhoz RP, Teive HA, et al. Olfactory impairment in familial ataxias. J Neurol Neurosurg Psychiatry . 2012;83(10):970-974. https://doi.org/10.1136/jnnp-2012-302770. Fatuzzo I, Niccolini GF, Zoccali F, et al. Neurons, Nose, and Neurodegenerative Diseases: Olfactory Function and Cognitive Impairment. Int J Mol Sci . 2023;24(3):2117. https://doi.org/10.3390/ijms24032117. Doty RL. Odor perception in neurodegenerative diseases. In: Doty R, editor. Handbook of olfaction and gustation. 2nd ed. New York: Marcel Dekker; 2003. p. 479-502. Mesholam RI, Moberg PJ, Mahr RN, et al. Olfaction in neurodegenerative disease: a meta-analysis of olfactory functioning in Alzheimer's and Parkinson's diseases. Arch Neurol . 1998;55(1):84-90. https://doi.org/10.1001/archneur.55.1.84. Doty RL, Li C, Mannon LJ, et al. Olfactory dysfunction in multiple sclerosis. N Engl J Med . 1997;336(26):1918-1919. https://doi.org/10.1056/nejm199706263362617. Doty RL, Li C, Mannon LJ, et al. Olfactory dysfunction in multiple sclerosis: relation to longitudinal changes in plaque numbers in central olfactory structures. Neurology . 1999;53(4):880-882. https://doi.org/10.1212/wnl.53.4.880. Sobel N, Prabhakaran V, Hartley CA, et al. Odorant-induced and sniff-induced activation in the cerebellum of the human. J Neurosci . 1998;18(21):8990-9001. https://doi.org/10.1523/jneurosci.18-21-08990.1998. Tucker BR. Report of a case of tumor of the ponto-cerebellar angle on the left side of the brain with bilateral loss of smell and disturbance of taste. Old Dominion J Med Surg . 1911;13:327-334. Peregud GM. Anosmia in tumors of the fourth ventricle. Russk Oto-laringol . 1931;24:101-105. Tran KD, Smutzer GS, Doty RL, et al. Reduced Purkinje cell size in the cerebellar vermis of elderly patients with schizophrenia. Am J Psychiat . 1998;155(9):1288-1290. https://doi.org/10.1176/ajp.155.9.1288. Parsons LM, Fox PT. Sensory and cognitive functions. Int Rev Neurobiol . 1997;41:255-271. https://doi.org/10.1016/s0074-7742(08)60355-4. Connelly T, Farmer JM, Lynch DR, et al. Olfactory dysfunction in degenerative ataxias. J Neurol Neurosurg Psychiatry . 2003;74(10):1435-1437. https://doi.org/10.1136/jnnp.74.10.1435. Su M, Wang S, Fang W, et al. Alterations in the limbic/paralimbic cortices of Parkinson's disease patients with hyposmia under resting-state functional MRI by regional homogeneity and functional connectivity analysis. Parkinsonism Relat Disord . 2015;21(7):698-703. https://doi.org/10.1016/j.parkreldis.2015.04.006. Wu S, Lu J, Wang J, et al. The study of functional MRI on neuronal activity of primary olfactory cortex in patients with subjective cognitive decline. Chin J Radiol . 2019;53(8):678-684. https://doi.org/10.3760/cma.j.issn.1005-1201.2019.08.004. Vroon A, Drukarch B, Bol JG, et al. Neuroinflammation in Parkinson's patients and MPTP-treated mice is not restricted to the nigrostriatal system: microgliosis and differential expression of interleukin-1 receptors in the olfactory bulb. Exp Gerontol . 2007;42(8):762-771. https://doi.org/10.1016/j.exger.2007.04.010. Savic I, Gulyas B, Larsson M, et al. Olfactory functions are mediated by parallel and hierarchical processing. Neuron . 2000;26(3):735-745. https://doi.org/10.1016/s0896-6273(00)81209-x. Ikai Y, Takada M, Mizuno N. Single neurons in the ventral tegmental area that project to both the cerebral and cerebellar cortical areas by way of axon collaterals. Neuroscience . 1994;61(4):925-934. https://doi.org/10.1016/0306-4522(94)90413-8. Alexander GE, DeLong MR, Strick PL. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci . 1986;9:357-381. https://doi.org/10.1146/annurev.ne.09.030186.002041. Oh YS, Kim JS, Hwang EJ, et al. Striatal dopamine uptake and olfactory dysfunction in patients with early Parkinson's disease. Parkinsonism Relat Disord . 2018;56:47-51. https://doi.org/10.1016/j.parkreldis.2018.06.022. Chauhan J, Hawrysh ZJ, Gee M, et al. Age-related olfactory and taste changes and interrelationships between taste and nutrition. J Am Diet Assoc . 1987;87(11):1543-1550. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4661059","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":332908513,"identity":"87b1ae80-e701-41b1-8d26-12fe7b81daab","order_by":0,"name":"Yiwen Liu","email":"","orcid":"","institution":"Anhui University of Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yiwen","middleName":"","lastName":"Liu","suffix":""},{"id":332908518,"identity":"f01ddb52-695c-4365-8e67-84add3413528","order_by":1,"name":"Tong Wu","email":"","orcid":"","institution":"Anhui University of Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Tong","middleName":"","lastName":"Wu","suffix":""},{"id":332908520,"identity":"ab30aeac-aa28-4d2d-a6c4-3597c7e4a9c9","order_by":2,"name":"Hao Zhou","email":"","orcid":"","institution":"Anhui University of Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Hao","middleName":"","lastName":"Zhou","suffix":""},{"id":332908521,"identity":"521468e5-c06f-43bf-8f15-0840b9f7bc84","order_by":3,"name":"Kepu Chen","email":"","orcid":"","institution":"Chinese Academy of Sciences","correspondingAuthor":false,"prefix":"","firstName":"Kepu","middleName":"","lastName":"Chen","suffix":""},{"id":332908522,"identity":"f3abac61-9b07-4f87-a2a8-4d2cc5879f4b","order_by":4,"name":"Yongsheng Han","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAApElEQVRIiWNgGAWjYBACAzBZISHHT6KWMxbGkg0kaWFsq0jcQLQWc4n0x58L50kwbmBgfvjoBjFaLGfkmEnP3CbBbM7AZmycQ5TDbuSwMfNuk2CzbOBhkyZSC9BhvHMkeAwOEK8lwUCat0FCggQtZ96YSc84JmEg2Uy0X44DHVZQU1ffz9788DFRWhgEEhiYwQxmopSDAP8BEhSPglEwCkbByAQAHzQs/KRmMYMAAAAASUVORK5CYII=","orcid":"","institution":"Wannan Medical College","correspondingAuthor":true,"prefix":"","firstName":"Yongsheng","middleName":"","lastName":"Han","suffix":""}],"badges":[],"createdAt":"2024-06-30 03:08:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4661059/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4661059/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":61431047,"identity":"01ea4d3c-1baf-48ae-80dd-465242dc802e","added_by":"auto","created_at":"2024-07-30 15:55:44","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":443301,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4661059/v1/f8561de5-3fa9-4078-96f2-3964494c9e74.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Quantitative Evaluation of Olfactory Function in Spinocerebellar Ataxia Type3 and Type1 in China: A Clinical Study","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eSpinocerebellar ataxias (SCAs) are a group of autosomal dominant inherited neurodegenerative diseases characterized by progressive ataxia, which can cause severe disability and premature death [1]. Although the motor symptoms of this disease, such as ataxia, have received widespread attention from neurologists, nonmotor symptoms, including olfactory impairment, sleep disturbances, anxiety, and depressive symptoms, have often been overlooked. The pathophysiological mechanisms of olfactory dysfunction in SCA remain unclear, and limited clinical research exists on olfactory function in SCA. Additionally, limited studies have assessed the relationship among olfactory function, severity of ataxia, and nonmotor symptoms in SCA. Therefore, this study aimed to explore the correlation between olfactory impairment and other clinical symptoms to improve our understanding of olfactory dysfunction in patients with SCA. We included 30 patients with SCA who visited the Neurology Institute Affiliated Hospital of Anhui University of Chinese Medicine over the past 3 years as research participants.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eInclusion Criteria\u003c/h2\u003e \u003cp\u003e(1) Patients diagnosed with SCA through genetic testing; (2) Absence of rhinitis or common cold symptoms; and (3) Absence of severe cognitive impairment and psychiatric symptoms.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eExclusion Criteria\u003c/h2\u003e \u003cp\u003e(1) Patients with cold, rhinitis, nasal polyps, or other lesions that may affect olfactory function and (2) History of head trauma, alcohol abuse, smoking, or drug abuse.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eClinical Data\u003c/h2\u003e \u003cp\u003eConsidering the aforementioned inclusion and exclusion criteria, we included 30 patients diagnosed with SCA who visited the Neurology Institute Affiliated Hospital of Anhui University of Chinese Medicine between August 2020 and August 2023. Among them, 18 were men and 12 were women, with an age range of 16\u0026ndash;71 (42.00\u0026thinsp;\u0026plusmn;\u0026thinsp;15.68) years. Additionally, 30 healthy controls were selected based on the exclusion criteria, matched for handedness, gender, age, and years of education with the patient group. Among the controls, 20 were men and 10 were women, with an age range of 18\u0026ndash;71 (42.25\u0026thinsp;\u0026plusmn;\u0026thinsp;15.31) years.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eNeurological function assessment\u003c/h2\u003e \u003cp\u003eThe neurology specialist, who received formal training, conducted the following tests before treatment: (1) International Cooperative Ataxia Rating Scale (ICARS): This test evaluated the severity of motor symptoms, including posture and gait disturbances, dynamic function, speech disorders, and eye movement in the SCA group. (2) Hamilton Anxiety Rating Scale (HAMA): This test assessed the level of anxiety in the SCA and control groups. (3) Hamilton Depression Rating Scale (HAMD): This test evaluated the depressive state of the SCA and control groups. (4) Pittsburgh Sleep Quality Index (PSQI): This test assessed the sleep quality of the SCA and control groups.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eOlfactory Function Assessment\u003c/h2\u003e \u003cp\u003eThis evaluation was conducted using the odor detection test developed by the Institute of Psychology, Chinese Academy of Sciences, which comprises three parts: (1) Olfactory Threshold Test: It comprises 20 odorant sticks numbered 1\u0026ndash;20 and 4 baseline sticks numbered 0. The odorant sticks presented the same odor with decreasing concentrations as the number increased, thereby forming a concentration gradient. The baseline sticks presented a baseline odor as the blank control. The threshold was determined by counting the number of odorant sticks where the odor was correctly identified by the participant with a 50% probability. During each trial, participants were blindfolded, and the odorant and baseline sticks were randomly presented in a sequence. Participants were asked to identify the stick that presented a stronger odor, allowing the evaluation of their ability to detect differences in odor concentration. The threshold was calculated using fitting software based on repeated tests, with a total score of 20 points. (2) Olfactory Discrimination Test: This test comprised 16 sets of sticks numbered 1\u0026ndash;16, with each set containing 3 sticks, and thus, totaling 48 sticks. Each set contained two sticks presenting the same odor and one stick presenting a different odor. During each trial, the participants were blindfolded, and they were presented with three sticks in a random order. The participants were asked to identify the stick with a different odor from the other two, indicating their ability to distinguish between different odor characteristics. Each correct answer scored 1 point, with a total score of 16 points. (3) Olfactory Identification Test: This test comprised 16 sticks numbered 1\u0026ndash;16, with each stick presenting a unique odor. The odors used were familiar to the Chinese population to avoid cultural differences and personal experience biases. During each trial, the participants were presented with one stick and provided four options to select the name of the odor. Each correct answer scored 1 point, with a total score of 16 points. The olfactory tests were conducted in an environment with effective air circulation and lacking other odors. The participants were not allowed to use perfume on the day of the test, and they refrained from consuming food and drinks 30 min before the test. All sticks were presented as felt-tip pens, with the tip placed approximately 1 cm in front of the nose. Each stick was shaken 5\u0026ndash;7 times, with the shaking range not exceeding the width of the nostrils. The total score of the olfactory test ranged from 0 to 52, with higher scores indicating better olfactory function.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eThe data analysis was conducted using SPSS version 25. For normally distributed continuous data, results were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (x\u0026thinsp;\u0026plusmn;\u0026thinsp;s), and between-group comparisons were performed using the independent samples t-test. For non-normally distributed continuous data, the results were presented as median and interquartile range [M (P25, P75)], and between-group comparisons were conducted using Wilcoxon\u0026rsquo;s rank-sum test. The Pearson correlation (for normally distributed data) and Spearman\u0026rsquo;s rank correlation analyses (for non-normally distributed data) were used to determine the correlation between olfactory function and clinical characteristics of patients with SCA. The differences were considered statistically significant at \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026le;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eNo statistically significant differences in gender, age, and education level were observed between the SCA and the control groups. The olfactory threshold, discrimination, identification, and total olfactory function scores were lower in the SCA group compared with the control group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Additionally, HAMA (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.009), HAMD (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.018), and PSQI (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) scores were higher in the SCA group compared with the control group (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The total olfactory identification score in the SCA group was negatively correlated with age (r\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.401, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.022). No correlation between olfactory function and disease duration, ICARS, HAMA, HAMD, or PSQI scores was observed in the SCA group (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical Data of the SCA and Control Groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eObservation Index\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSCA Group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl Group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender (M/F)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15/15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20/10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42.73\u0026thinsp;\u0026plusmn;\u0026thinsp;13.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44.63\u0026thinsp;\u0026plusmn;\u0026thinsp;15.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.615\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisease Duration (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.00\u0026thinsp;\u0026plusmn;\u0026thinsp;3.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOlfactory Threshold (20 points)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.90\u0026thinsp;\u0026plusmn;\u0026thinsp;4.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.78\u0026thinsp;\u0026plusmn;\u0026thinsp;3.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.000*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOlfactory Discrimination (16 points)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.27\u0026thinsp;\u0026plusmn;\u0026thinsp;2.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.25\u0026thinsp;\u0026plusmn;\u0026thinsp;3.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.000*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOlfactory Identification (16 points)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.87\u0026thinsp;\u0026plusmn;\u0026thinsp;2.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.36\u0026thinsp;\u0026plusmn;\u0026thinsp;4.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOlfactory Total Score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28.03\u0026thinsp;\u0026plusmn;\u0026thinsp;5.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42.43\u0026thinsp;\u0026plusmn;\u0026thinsp;5.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.000*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICARS Score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31.20\u0026thinsp;\u0026plusmn;\u0026thinsp;6.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHAMA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.03\u0026thinsp;\u0026plusmn;\u0026thinsp;4.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.35,5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.005*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHAMD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.10\u0026thinsp;\u0026plusmn;\u0026thinsp;4.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.3,6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.027*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePSQI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.56\u0026thinsp;\u0026plusmn;\u0026thinsp;4.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.25,3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.000*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003e*Statistically significant at\u003cem\u003er\u003c/em\u003e\u0026thinsp;\u0026le;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCorrelation between Olfactory Function and Motor and Nonmotor Symptoms in the SCA Group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eOlfactory\u003c/p\u003e \u003cp\u003eThreshold\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eOlfactory\u003c/p\u003e \u003cp\u003eDiscrimination\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eOlfactory\u003c/p\u003e \u003cp\u003eIdentification\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003eOlfactory Total\u003c/p\u003e \u003cp\u003eScore\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003er P\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003er P\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003er P\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003er P\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0. 139\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.238\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.276\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0. 135\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.377\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.041*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e-0.420\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.027*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisease Duration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.251\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.359\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.212\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 259\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.414\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e-0.221\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.238\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICARS score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.085\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.582\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.314\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.028\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.882\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e-0.039\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.707\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHAMA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.052\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.712\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.093\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.612\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.319\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0. 221\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e-0. 199\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.366\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHAMD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.075\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0 115\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.357\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e-0.203\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.508\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePSQI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0. 213\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.053\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.692\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0. 263\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.402\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e-0.136\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.711\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003e*Statistically significant at\u003cem\u003er\u003c/em\u003e\u0026thinsp;\u0026le;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eOlfactory dysfunction is commonly observed in various neurodegenerative diseases, and our clinical observations indicate that patients with SCA exhibit olfactory impairment to a certain extent. Several studies have highlighted the close relationship between the cerebellum and olfactory function. Ivanka Savic et al. [1] used functional magnetic resonance imaging (fMRI) to reveal the activation of the cerebellum during olfactory stimulation. Juan Fernandez-Ruiz et al. [2] were the first to confirm olfactory dysfunction in patients with cerebellar damage. However, notably, the degree of olfactory impairment in patients with SCA is not as severe as those with Parkinson\u0026rsquo;s disease (PD) or Alzheimer\u0026rsquo;s disease (AD). Furthermore, studies have revealed a close relationship between olfaction and cognitive function in patients with SCA. V\u0026aacute;zquez-P\u0026eacute;rez et al. [3] investigated olfactory function in 53 patients with SCA2 and 53 healthy controls and revealed significantly lower olfactory scores in the SCA2 group compared with the healthy control group. Moreover, a significant correlation was observed between the olfactory scores and Mini-Mental State Examination (MMSE) scores (p\u0026thinsp;=\u0026thinsp;0.03). In this study, we evaluated the olfactory function of 30 patients with SCA (primarily SCA1 and SCA3 subtypes) and analyzed its correlation with motor impairment, anxiety and depression status, and sleep quality.\u003c/p\u003e \u003cp\u003eThe results of this study suggest that, compared with the control group, patients in the SCA group exhibit decreased olfactory threshold, discrimination, and identification, consistent with the findings from previous studies. Galvez et al. [4] demonstrated that olfactory discrimination and identification abilities were significantly impaired in patients with SCA7 while their olfactory threshold remained within normal levels, suggesting that neurological damage in patients with SCA7 affects olfaction but preserves olfactory perception ability. Similarly, Braga-Neto et al. [5] found a significant decrease in the olfactory ability of patients having SCA3, with the degree of olfactory dysfunction correlating with patient age, education level, smoking status, and MMSE scores. Additionally, significant differences in olfactory function have been observed among different subtypes of SCA. Mariana Moscovich et al. [6] conducted olfactory tests on patients with SCA10 and SCA2, and the results indicated olfactory impairments in patients with SCA2 but no significant olfactory defects in patients with SCA10 [7].\u003c/p\u003e \u003cp\u003eThe mechanism underlying olfactory dysfunction remains unclear, but the decrease in olfactory threshold is typically associated with damage to the olfactory epithelium and olfactory sensory neurons [8]. This damage is most commonly attributed to chronic rhinitis [8]. Therefore, it is crucial that studies evaluating olfaction in patients with SCA exclude the influence of peripheral olfactory system damage. Numerous studies have found olfactory dysfunction in various neurological disorders, including idiopathic PD [9, 10], AD, schizophrenia, and multiple sclerosis (MS).\u003c/p\u003e \u003cp\u003eOlfaction and movement disorders share a close relationship, with olfactory dysfunction serving as an early indicator for the onset of certain diseases. In PD, the prevalence of olfactory loss exceeds that of tremor. In patients with MS, olfactory dysfunction is significantly negatively correlated with the number of active lesions in the primary and secondary olfactory cortices [11, 12]. Traditionally, the human cerebellum is the center for motor coordination; it contains more neurons than other parts of the brain and is structurally connected to all major branches of the central nervous system, including the cerebrum, basal ganglia, diencephalon, limbic system, brainstem, and the spinal cord [11, 12]. The cerebellum also plays a role in olfactory function [13], and the evidence supporting its involvement in olfactory processing includes the following: (A) reports of olfactory defects in patients with cerebellar or near-cerebellar tumors [14, 15]; (B) signs of cerebellar abnormalities in patients with olfactory loss-related disorders, such as schizophrenia [16]; and (C) fMRI demonstrating cerebellar activation during olfactory processes [2]. fMRI studies revealed activation in the posterior lateral hemisphere of the cerebellum following odor induction, activation of the uvula and posterior quadrangular lobes following odor recognition tasks, and activation of the right central lobule and vermis solely evoked through olfaction [17]. (D) T Connelly et al. conducted the University of Pennsylvania Smell Identification Test on patients with ataxia, primarily caused by cerebellar pathology (SCA and related disorders) and Friedrich\u0026rsquo;s ataxia (a condition primarily associated with loss of input cerebellar pathways). The results showed that olfactory test scores were significantly lower in patients with cerebellar disease compared with the control group [18].\u003c/p\u003e \u003cp\u003eThe olfactory dysfunction in SCA may be related to disruptions in brain network function associated with olfaction. fMRI conducted on the central olfactory system revealed that patients with PD who possess olfactory dysfunction exhibit a significant decrease in regional homogeneity in traditional olfactory regions, such as the amygdala, olfactory gyrus, orbitofrontal gyrus, parahippocampal gyrus, and insula, and few nontraditional olfactory centers, such as the prefrontal gyrus and temporal pole, suggesting that besides traditional olfactory core regions, other brain regions also participate in olfaction [19]. For example, the decrease in olfactory threshold is correlated with the left primary olfactory cortex [20]; odor discrimination tasks are associated with the frontal and temporal lobes and the limbic system such as the orbitofrontal cortex and hippocampus [21]; odor recognition tasks activate the cerebellum, temporal lobe, and parietal lobe cortex [22]; and the cerebellum receives olfactory inputs from the piriform cortex via the ventral striatum [23]. The basal ganglia, as a core component of the neural circuitry hypothesis, can receive signal inputs from the primary olfactory cortex, including the olfactory tubercle, during olfactory tasks [24], and patients with PD having olfactory dysfunction exhibit a significant decrease in dopamine transporter uptake in the bilateral caudate nucleus and the left anterior and posterior putamen [25].\u003c/p\u003e \u003cp\u003eIn this study, the age of the patients with SCA was negatively correlated with various olfactory scores, indicating that age is an important risk factor for olfactory dysfunction [26]. The HAMA, HAMD, and PSQI scores were higher in the SCA group than the control group, suggesting that most patients with SCA have anxiety, depression, and sleep disorders. However, no correlations between the scores of HAMA, HAMD, and PSQI and olfactory function were observed in the SCA group in this study.\u003c/p\u003e \u003cp\u003eThe olfactory sticks used in this study were developed by the Institute of Psychology, Chinese Academy of Sciences. The sticks offer the advantages of convenience, accuracy, and high sensitivity. The selected odors are familiar to the Chinese population; nonirritable; and enable the assessment of the sensitivity level of odor detection and odor perception and the ability to perceive odor characteristics to determine their association with odor concepts in the memory system. These sticks meet the requirements for scientific research and clinical examinations.\u003c/p\u003e \u003cp\u003eIn conclusion, this study demonstrates a high prevalence of olfactory dysfunction in patients with SCA, characterized by a comprehensive decrease in olfactory threshold, discrimination, and identification functions. No correlation is observed between olfactory dysfunction in SCA and motor symptoms, pain, anxiety, depression, or sleep disturbances. However, this study has certain limitations. First, the sample size was relatively small, which may lead to biased results. Second, fMRI examinations were not conducted to further explore the neurobiological mechanisms underlying olfactory dysfunction in SCA. Lastly, no follow-up investigation was conducted to determine the relationship between olfactory dysfunction and treatment outcomes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics Approval:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study has been approved by the Ethics Committee of Affiliated Hospital, Institute of Neurology, Anhui University of Chinese Medicine under approval number 2020 Lunzi (21). The approval was granted on November 01, 2020. The research conducted in this study adheres to the ethical guidelines set forth by the Ethics Committee of Affiliated Hospital, Institute of Neurology, Anhui University of Chinese Medicine .\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Participate:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll participants involved in this study provided informed consent prior to their participation. They were informed about the study\u0026apos;s purpose, procedures, potential risks, and benefits. Participants were assured of their voluntary participation and their right to withdraw from the study at any time without consequences.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConfidentiality:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants\u0026apos; confidentiality and anonymity have been strictly maintained throughout the study. Any personal information collected has been kept confidential and will only be used for research purposes. Data will be reported in aggregate form to ensure individual privacy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContact Information:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFor any questions regarding ethics approval, consent procedures, or participant rights, please contact:\u003c/p\u003e\n\u003cp\u003e[corresponding author:Yongsheng Han] [Affiliated Hospital, Institute of Neurology, Anhui University of Traditional Chinese Medicine] [Email Address:[email protected]] [Phone Number:13866159323]；\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no Competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by National Natural Science Foundation of China (8177425); Natural Science Foundation of Anhui Province (1808085MH245); and Key Research and Development Program of Anhui Province (S202004a07020061).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and Informed consent statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study has been approved by the Ethics Board of Anhui University of Chinese Medicine. Written informed consent was obtained from the patient to participate.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication of the clinical details was obtained from the patient.\u003c/p\u003e\n\u003cp\u003eData availability\u003c/p\u003e\n\u003cp\u003eThe datasets generated during and/or analyzed during the current study are not publicly available, but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u003c/strong\u003e\u003cstrong\u003e\u0026rsquo;\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization: Yongsheng Han; Writing\u0026mdash;original draft: Yiwen Liu and Hao Zhou; Writing\u0026mdash;review and editing: Tong Wu and Kepu Chen. Approval of final manuscript: all authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRelevant information is available from the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to express our sincere gratitude to all individuals and organizations who contributed to the completion of this study. Their support and assistance were invaluable in the research process.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSavic I. Brain imaging studies of the functional organization of human olfaction.\u003cem\u003e \u003c/em\u003e\u003cem\u003eChem Senses\u003c/em\u003e. 2005;30(Suppl 1):i222-223. https://doi.org/10.1093/chemse/bjh194.\u003c/li\u003e\n\u003cli\u003eFernandez-Ruiz J, D\u0026iacute;az R, Hall-Haro C, et al. Olfactory dysfunction in hereditary ataxia and basal ganglia disorders.\u003cem\u003e Neuroreport\u003c/em\u003e. 2003;14(10):1339-1341. https://doi.org/10.1097/01.wnr.0000077551.91466.d3.\u003c/li\u003e\n\u003cli\u003eVel\u0026aacute;zquez-P\u0026eacute;rez L, Fernandez-Ruiz J, D\u0026iacute;az R, et al. Spinocerebellar ataxia type 2 olfactory impairment shows a pattern similar to other major neurodegenerative diseases.\u003cem\u003e J Neurol\u003c/em\u003e. 2006;253(9):1165-1169. https://doi.org/10.1007/s00415-006-0183-2.\u003c/li\u003e\n\u003cli\u003eGalvez V, Diaz R, Hernandez-Castillo CR, et al. Olfactory performance in spinocerebellar ataxia type 7 patients.\u003cem\u003e Parkinsonism Relat Disord\u003c/em\u003e. 2014;20(5):499-502. https://doi.org/10.1016/j.parkreldis.2014.01.024.\u003c/li\u003e\n\u003cli\u003eBraga-Neto P, Felicio AC, Pedroso JL, et al. Clinical correlates of olfactory dysfunction in spinocerebellar ataxia type 3.\u003cem\u003e Parkinsonism Relat Disord\u003c/em\u003e. 2011;17(5):353-356. https://doi.org/10.1016/j.parkreldis.2011.02.004.\u003c/li\u003e\n\u003cli\u003eMoscovich M, Munhoz RP, Moro A, et al. Olfactory Function in SCA10.\u003cem\u003e Cerebellum\u003c/em\u003e. 2019;18(1):85-90. https://doi.org/10.1007/s12311-018-0954-1.\u003c/li\u003e\n\u003cli\u003eMoscovich M, Munhoz RP, Teive HA, et al. Olfactory impairment in familial ataxias.\u003cem\u003e J Neurol Neurosurg Psychiatry\u003c/em\u003e. 2012;83(10):970-974. https://doi.org/10.1136/jnnp-2012-302770.\u003c/li\u003e\n\u003cli\u003eFatuzzo I, Niccolini GF, Zoccali F, et al. Neurons, Nose, and Neurodegenerative Diseases: Olfactory Function and Cognitive Impairment.\u003cem\u003e Int J Mol Sci\u003c/em\u003e. 2023;24(3):2117. https://doi.org/10.3390/ijms24032117.\u003c/li\u003e\n\u003cli\u003eDoty RL. Odor perception in neurodegenerative diseases. In: Doty R, editor. Handbook of olfaction and gustation. 2nd ed. New York: Marcel Dekker; 2003. p. 479-502.\u003c/li\u003e\n\u003cli\u003eMesholam RI, Moberg PJ, Mahr RN, et al. Olfaction in neurodegenerative disease: a meta-analysis of olfactory functioning in Alzheimer\u0026apos;s and Parkinson\u0026apos;s diseases.\u003cem\u003e Arch Neurol\u003c/em\u003e. 1998;55(1):84-90. https://doi.org/10.1001/archneur.55.1.84.\u003c/li\u003e\n\u003cli\u003eDoty RL, Li C, Mannon LJ, et al. Olfactory dysfunction in multiple sclerosis.\u003cem\u003e N Engl J Med\u003c/em\u003e. 1997;336(26):1918-1919. https://doi.org/10.1056/nejm199706263362617.\u003c/li\u003e\n\u003cli\u003eDoty RL, Li C, Mannon LJ, et al. Olfactory dysfunction in multiple sclerosis: relation to longitudinal changes in plaque numbers in central olfactory structures.\u003cem\u003e Neurology\u003c/em\u003e. 1999;53(4):880-882. https://doi.org/10.1212/wnl.53.4.880.\u003c/li\u003e\n\u003cli\u003eSobel N, Prabhakaran V, Hartley CA, et al. Odorant-induced and sniff-induced activation in the cerebellum of the human.\u003cem\u003e J Neurosci\u003c/em\u003e. 1998;18(21):8990-9001. https://doi.org/10.1523/jneurosci.18-21-08990.1998.\u003c/li\u003e\n\u003cli\u003eTucker BR. Report of a case of tumor of the ponto-cerebellar angle on the left side of the brain with bilateral loss of smell and disturbance of taste.\u003cem\u003e Old Dominion J Med Surg\u003c/em\u003e. 1911;13:327-334. \u003c/li\u003e\n\u003cli\u003ePeregud GM. Anosmia in tumors of the fourth ventricle.\u003cem\u003e Russk Oto-laringol\u003c/em\u003e. 1931;24:101-105. \u003c/li\u003e\n\u003cli\u003eTran KD, Smutzer GS, Doty RL, et al. Reduced Purkinje cell size in the cerebellar vermis of elderly patients with schizophrenia.\u003cem\u003e Am J Psychiat\u003c/em\u003e. 1998;155(9):1288-1290. https://doi.org/10.1176/ajp.155.9.1288.\u003c/li\u003e\n\u003cli\u003eParsons LM, Fox PT. Sensory and cognitive functions.\u003cem\u003e \u003c/em\u003e\u003cem\u003eInt Rev Neurobiol\u003c/em\u003e. 1997;41:255-271. https://doi.org/10.1016/s0074-7742(08)60355-4.\u003c/li\u003e\n\u003cli\u003eConnelly T, Farmer JM, Lynch DR, et al. Olfactory dysfunction in degenerative ataxias.\u003cem\u003e \u003c/em\u003e\u003cem\u003eJ Neurol Neurosurg Psychiatry\u003c/em\u003e. 2003;74(10):1435-1437. https://doi.org/10.1136/jnnp.74.10.1435.\u003c/li\u003e\n\u003cli\u003eSu M, Wang S, Fang W, et al. Alterations in the limbic/paralimbic cortices of Parkinson\u0026apos;s disease patients with hyposmia under resting-state functional MRI by regional homogeneity and functional connectivity analysis.\u003cem\u003e \u003c/em\u003e\u003cem\u003eParkinsonism Relat Disord\u003c/em\u003e. 2015;21(7):698-703. https://doi.org/10.1016/j.parkreldis.2015.04.006.\u003c/li\u003e\n\u003cli\u003eWu S, Lu J, Wang J, et al. The study of functional MRI on neuronal activity of primary olfactory cortex in patients with subjective cognitive decline.\u003cem\u003e \u003c/em\u003e\u003cem\u003eChin J Radiol\u003c/em\u003e. 2019;53(8):678-684. https://doi.org/10.3760/cma.j.issn.1005-1201.2019.08.004.\u003c/li\u003e\n\u003cli\u003eVroon A, Drukarch B, Bol JG, et al. Neuroinflammation in Parkinson\u0026apos;s patients and MPTP-treated mice is not restricted to the nigrostriatal system: microgliosis and differential expression of interleukin-1 receptors in the olfactory bulb.\u003cem\u003e Exp Gerontol\u003c/em\u003e. 2007;42(8):762-771. https://doi.org/10.1016/j.exger.2007.04.010.\u003c/li\u003e\n\u003cli\u003eSavic I, Gulyas B, Larsson M, et al. Olfactory functions are mediated by parallel and hierarchical processing.\u003cem\u003e Neuron\u003c/em\u003e. 2000;26(3):735-745. https://doi.org/10.1016/s0896-6273(00)81209-x.\u003c/li\u003e\n\u003cli\u003eIkai Y, Takada M, Mizuno N. Single neurons in the ventral tegmental area that project to both the cerebral and cerebellar cortical areas by way of axon collaterals.\u003cem\u003e Neuroscience\u003c/em\u003e. 1994;61(4):925-934. https://doi.org/10.1016/0306-4522(94)90413-8.\u003c/li\u003e\n\u003cli\u003eAlexander GE, DeLong MR, Strick PL. Parallel organization of functionally segregated circuits linking basal ganglia and cortex.\u003cem\u003e Annu Rev Neurosci\u003c/em\u003e. 1986;9:357-381. https://doi.org/10.1146/annurev.ne.09.030186.002041.\u003c/li\u003e\n\u003cli\u003eOh YS, Kim JS, Hwang EJ, et al. Striatal dopamine uptake and olfactory dysfunction in patients with early Parkinson\u0026apos;s disease.\u003cem\u003e Parkinsonism Relat Disord\u003c/em\u003e. 2018;56:47-51. https://doi.org/10.1016/j.parkreldis.2018.06.022.\u003c/li\u003e\n\u003cli\u003eChauhan J, Hawrysh ZJ, Gee M, et al. Age-related olfactory and taste changes and interrelationships between taste and nutrition.\u003cem\u003e J Am Diet Assoc\u003c/em\u003e. 1987;87(11):1543-1550. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Spinocerebellar ataxia, Olfactory function, Olfactory test, Ataxia, Nonmotor symptoms","lastPublishedDoi":"10.21203/rs.3.rs-4661059/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4661059/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjectives: \u003c/strong\u003eThis study investigates olfactory function and clinical characteristics in spinocerebellar ataxia (SCA) patients, exploring the link between motor and nonmotor symptoms.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eIn a study conducted at the Neurology Institute Affiliated Hospital of Anhui University of Chinese Medicine, 30 spinocerebellar ataxia (SCA) patients diagnosed from August 2020 to August 2023 were matched with 30 controls. Olfactory functions were evaluated using the Institute of Psychology's olfactory test. The SCA group's ataxia severity was assessed with the International Cooperative Ataxia Rating Scale (ICARS). Variations in Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Pittsburgh Sleep Quality Index (PSQI) scores were compared between groups, and correlations between olfactory function and SCA symptoms were examined.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eIn the SCA group, olfactory scores were significantly lower compared to controls (\u003cem\u003eP \u003c/em\u003e\u0026lt; 0.001). SCA patients had higher HAMA (\u003cem\u003eP\u003c/em\u003e = 0.005), HAMD (\u003cem\u003eP\u003c/em\u003e= 0.02), and PSQI (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001) scores. However, Olfactory identification correlated negatively with age (r = −0.377, \u003cem\u003eP \u003c/em\u003e= 0.041) in SCA patients. No significant correlations were found between olfactory function and disease duration, ICARS, HAMA, HAMD, or PSQI scores in the SCA group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eThe olfactory dysfunction is prevalent in SCA patients, But there was no significant correlation between motor symptoms and non-motor symptoms.\u003c/p\u003e","manuscriptTitle":"Quantitative Evaluation of Olfactory Function in Spinocerebellar Ataxia Type3 and Type1 in China: A Clinical Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-30 15:47:38","doi":"10.21203/rs.3.rs-4661059/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-08-07T19:20:06+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-06T05:49:44+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-30T15:27:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"12132277233638461716640284680720727049","date":"2024-07-28T17:02:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"24610432188490565795000999037071537815","date":"2024-07-23T16:22:18+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-22T22:57:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"143373273208122712321939475588946171934","date":"2024-07-13T12:27:31+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-07-11T11:39:57+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-07-09T19:19:05+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-05T12:06:28+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-07-05T12:05:58+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Neurology","date":"2024-06-30T03:02:54+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"13aeb3ec-d0dd-4650-89be-148f4e6cc5c5","owner":[],"postedDate":"July 30th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-03T17:23:17+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-30 15:47:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4661059","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4661059","identity":"rs-4661059","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}