| Background:Parkinson’s disease (PD) is one of the most common neurodegenerative disease. The prevalence of PD is increasing rapidly recent years. It is estimated that there are about 200 million patients with Parkinson’s disease in China. The new onset of Parkinson’s disease rises up to more than 10 million each year. The incidence of PD is about 1.7% in the population over the age of 65 and 6.1% in the population over the age of 90. The typical manifestations are motor symptoms characterized by muscle rigidity, rest tremor, bradykinesia and gait disorders. The diagnosis of Parkinson’s disease is still not perfect. The clinical tools and criteria still have limitations in specificity and sensitivity. Doctors usually make diagnosis by clinical manifestations, past history, signs and response to levodopa. MRI and CT test can exclude other neurological diseases but has no specificity and sensitivity in diagnosis. Usually,the accuracy of PD clinical diagnosis is 75%-80%,compared with pathology. To find more biomarkers for PD diagnosis is one of the most pressing problems.In addition to typical motor symptoms of Parkinson’s disease, there are also a variety of non-motor symptoms such as sleep disorders, depression, visual impairment, olfactory loss, constipation and so on, some of which can be shown earlier than motor symptoms. In recent years, researchers have paid much attention to olfactory disorders of PD. The olfactory system of human body consists of various neurotrophic factors, which are all involved in the the olfactory pathway. And the stem cells of olfactory system are the most metabolically active in the brain. Based on the results of correlational research,45-90% patients with Parkinson’s show smell abnormalities of different degree, which may appear far earlier than motor symptoms. Different from the conventional criteria proposed by UK brain bank, olfactory loss becomes one of the four supportive criteria in the MDS Clinical Diagnostic Criteria for Parkinson’s Disease in 2015.More and more studies have been made on olfactory loss, however, there is not a unified operating standard to test olfactory of PD patients. Some of the researchers in China apply "Five tastes smell test fluid", which is developed by Institute of semiconductors, Chinese academy of sciences,to conjoint analysis detection threshold and recognition capability of PD patients. The sensitivity and specificity of detecting PD were 74.0% and 91.7%,respectively.But it is not widely used clinically because of time consuming and complexity. Researchers abroad make more use of Olfactory test bar and the Smell Identification Test of university of Pennylvania. The former assess the olfactory factors of the subjects in three areas: recognition threshold, identification and distinction. While the latter mainly detects the identification ability of the patients. And it is more time-consuming and easy to cause odor fatigue. For now, Simple olfactometry is in common use domestically. Constipation is another common non-motor symptoms in Parkinson’s disease.Certain studies have shown that constipation is related to the density of substantia nigra neurons in the brain. While more researchers consider that it is abnormal accumulation of α-synuclein in enteric nerve plexus which results in motility disorders of the colon. Depression is also common in PD patients, which may have relationship with 5-HT,norepinephrine and dopamine D3 receptors.5-HT levels of PD patients are lower than normal in caudate nucleus, olfactory bulb, hippocampus, cingulate gyrus and thalamus.As we can see in PET, some regions in the brain of Parkinson’s patients with depression showed hypometabolism, such as caudate nucleus, prefrontal orbit, medial prefrontal cortex and cingulate gyrus.It indicated that emotional disorders may be related to metabolic disorders of basal ganglia and prefrontal areas, which are involved in emotion regulation. Numerous studies have shown that hyperuricemia has protective effects to dopaminergic neuron, which can be progressively damaged by oxidative stress. Correspondingly, there is less study on the degree of blood uric acid and olfactory loss. Until now, relationships between olfactory loss and other factors of idiopathic Parkinson’s disease is not clear, such as constipation, depression, types and severity of the disease, duration of Parkinsonism and levels of blood uric acid. We will explore these issues in this study and try to provide the foundation for the early diagnosis of Parkinson’s disease.Objective:The aim of this study was to investigate the relationships between olfactory loss and other factors of idiopathic Parkinson’s disease, such as constipation, depression, types and levels of blood uric acid, and to provide the foundation for the early diagnosis.Method:1. The study included 62 PD patients with olfactory loss (olfactory loss group) and 58 patients without olfactory disorders(normal olfaction group).Age and sex-matched 60 normal subjects were served as control group.Simple olfactometry was used and all patients are from the clinic of Qilu hospital of Shandong University.2. For all subjects, questionnaires including age, gender, disease duration and so on were performed. Part III of Unified Parkinson’s Disease Rating Scale (UPDRS) and modified Hoehn and Yahr Scale score were used to evaluate the severity of the disease. We used Hamilton depression scale(HAMD) to assess mental state, ROMAIII to assess constipation, and tested the level of blood uric acid.3. Comparison between groups was done with independent sample T-test and chi-square test.And the influence diversity of Constipation, depression, types and severity of the disease, duration and levels of blood uric acid with the one way ANOVA is presented. P<0.05 denotes the difference possessing statistical significance. The data was analyzed by the software of SPSS 20.Results:1.There are 58 patients in olfactory loss group including 32 (55.2%) male and 26 (44.8%) female, mean (65.1±6.8) years. The average age of onset was 61.6±7.6 years old and the mean disease course of parkinsonism was (4.0±3.2) years. In the normal olfaction group, there are 62 PD patients, including 33 (53.2%) male and 29 (46.8%) female, mean (66.7±6.4) years. In this group, the average age of onset was (59.2±6.8)years old and the mean disease course of parkinsonism was (3.3±2.4)years. The control group consists of 35(58.3%) male and 25(41.7%) female, aged between mean(64.5±7.1) years. There were no statistical differences comparatively among different groups at gender, age, course and state of disease(P>0.05).2.The difference of the degree of constipation, depression and blood uric acid between olfactory loss group and control group is significant. (X2=37.465, P=9.3E10; tD=4.32,P=0.005; tD=3.742, P=0.01)The same method was used to compare normal olfaction group to control group. The difference also showed significant. (X2=17.391, P=3.0E5; tD=4.166,P=0.006; tD=2.780,P=0.03) The difference of the degree of constipation between the two PD group is significant. (X2=5.534, P=0.03) the degree of depression and blood uric acid showed no significant difference. (tD=0.162,P=0.089; Z=0.961,P=0.37)Conclusions:The study indicated that olfactory loss is relative with constipation in idiopathic Parkinson’s disease and it is independent of depression and blood uric acid. Simple olfactometry has important reference value in the diagnosis of Parkinson’s disease... |
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