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This article is to investigate the effect of piperine on the small intestine of mice with Parkinson's disease with dementia(PDD). Ninety-six C57 BL/6 mice of SPF grade were randomly divided into 8 groups(male, 12 in each group): normal group, model group, autophagy inhibitor group(6-amino-3-methylpurine, 3 MA, 30 mg·kg~(-1)), autophagy activator group(rapamycin, 1 mg·kg~(-1)), low, medium, and high dose piperine groups(10, 20, 40 mg·kg~(-1)), and medopar group(112.5 mg·kg~(-1)). Except for the normal group, mice in each group were injected subcutaneously with reserpine(0.1 mg·kg~(-1)) once every 48 hours for 40 days. In addition, on the 20 th day of administration, except for the normal group, the mice in the other groups were subjected to bilateral common carotid artery occlusion to finally prepare PDD models. At the same time, each group was given the corresponding drug treatment once a day for 40 days. After the last administration, the behavioral changes of mice were observed by autonomic activity experiment and hot plate experiment. The expression levels of α-synuclein(α-syn) and tyrosine hydroxylase(TH) in the small intestine were detected by immunohistochemistry. The expression levels of beclin-1, microtubule-associated protein 1 light chain 3 B(LC3 B) and p62 in the small intestine were detected by immunofluorescence assay. Hematoxylin-eosin staining was used to observe the pathological morphology of small intestine tissues in each group. Enzyme-linked immunosorbent assay was adopted for detection of β-amyloid precursor protein(APP), p-tau, acetylcholine transferase(ChAT), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in small intestine. Real-time fluorescent quantitative polymerase chain reaction was used to detect the expression of α-syn, TH, beclin-1, microtubule-associated protein 1 light chain 3(LC3), and p62 mRNA and mmu-miR-99 a-5 p in the small intestine. The results of this study showed that, as compared with the model group, the number of activities, the expression levels of ChAT, TH, and p62 were significantly increased in the 3 MA group, the various piperine dose groups, and the medopar group(P<0.05), and their first foot licking time was shortened; APP, p-tau, IL-6, TNF-α, α-syn, beclin-1, LC3 B and mmu-miR-99 a-5 p expression levels were significantly reduced(P<0.05). However, as compared with the model group, the number of activities, ChAT, TH, and p62 expression levels in the rapamycin group were significantly reduced(P<0.05), and the APP, p-tau, IL-6, TNF-α, α-syn, beclin-1, LC3 B and mmu-miR-99 a-5 p expression levels were significantly increased(P<0.05). As compared with the 3 MA group, the number of activities, ChAT, TH, and p62 expression levels were significantly reduced in the low and medium dose piperine groups and rapamycin group(P<0.05); howe-ver, their first foot licking time was significantly prolonged, APP, p-tau, IL-6, TNF-α, α-syn, beclin-1, LC3 B and mmu-miR-99 a-5 p expression levels were increased significantly(P<0.05). As compared with the medopar group, the number of activities, ChAT, TH, and p62 expression levels were significantly reduced in low dose piperine group and rapamycin group(P<0.05), but their first foot licking time was significantly extended, and APP, p-tau, IL-6, TNF-α, α-syn, beclin-1, LC3 B and mmu-miR-99 a-5 p expression levels were significantly increased(P<0.05). In addition, as compared with the normal group, the small intestinal epithelial cells of the model group and the rapamycin group were shed off a lot, with severe damages of intestinal mucosa as well as edema and shedding of the small intestine villi. After administration of the therapeutic interventions, the small intestinal epithelial cells of the 3 MA group, each dose group of piperine, and the medopa group were slightly damaged and the villi were slightly shed off. In summary, piperine has a protective effect on the small intestine of PDD model mice, showing reduced expression of mmu-miR-99 a-5 p, pro-inflammatory factors and autophagy factors, and the mechanism of slowing PDD pathological symptoms may be related to the inhibition of autophagy.
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Animals , Male , Mice , Alkaloids , Autophagy , Benzodioxoles , Dementia , Intestine, Small , Parkinson Disease , Piperidines , Polyunsaturated AlkamidesABSTRACT
Parkinson's disease(PD) is a progressive neurodegenerative disease characterized by motor symptoms such as rigidity, rest tremor, and bradykinesia. However, evidence demonstrated that PD encompasses several non-motor disturbances as well, such as cognitive impairment. Mild cognitive impairment can be present since early stages of the disease, and characterized by impairments in several cognitive domains including executive functions, attention, and visuospatial skills, language, and memory; In advanced stages of the disease, cognitive defects can develop into dementia and there is a considerable heterogeneity in the cognitive impairments. In this review, we focus on the clinical characteristics, biomarkers, and drug and non-drug treatments of cognitive impairment in Parkinson's disease, hoping to provide help for clinical practice.
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Objective To compare the cognitive functions and behavioral and psychological symptoms between Parkinson disease with dementia(PDD)and Alzheimer disease(AD). Methods Seventy-five cases with AD and 63 cases with PDD were recruited in this study. The mini mental state examination (MMSE), Montreal cognitive assessment (MoCA)and activities of daily living scale (ADL)were used to evaluate the cognitive impairment.The Chinese version of neuropsychiatric questionnaire(CNPI)was used to measure behavioral and psychological symptoms. Results ①Cognitive assessments:there were no statistically significant differences in total MMSE scores,total MoCA scores,total CNPI scores and ADL scores between AD patients and PDD patients (P>0.05).The sub-items of MoCA showed that memory loss was more severe in AD patients(2.17±0.65)than in PDD patients(2.44±0.50)(P<0.01).Visuospatial/executive dysfunction was more severe in PDD patients(3.73±0.70)than in AD patients(4.01±0.76)(P<0.05).②The items of CNPI showed that ADD patients had lower scores in the items of CNPI compared with the PDD patients (15.31±3.16 vs 19.41±3.52). The sub-items of CNPI showed that the most common mental symptoms in PDD patients were hallucination, depression, and agitation, which were 55.6%, 54%, and 52.4%, respectively Compared with the AD patients (P<0.05). On the contrary, compared with PDD patients, the most common mental symptoms were anxiety, apathy and irritability in AD patients, which were 53.3%, 52% and 49.3%, respectively (P<0.05). Conclusion Patients with AD and PDD exhibit different characteristics in cognitive functions and behavioral and psychological symptoms.Neuropsychological tests combined with clinical history can be helpful for differentiation between AD and PDD in dementia patients.
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Objective To observe the efficacy and safety of the cocktail therapy to treat patients with Parkinson's disease with dementia ( PDD) . Methods Sixty patients with PDD were randomly divided into treatment group(30 cases)and control group(30 cases). The dose 10 mg of donepezil hydrochloride was taken 1 time a day in the control group;on the basis,the dose 0. 2 g of butylphthalide soft capsules was taken pre-dinner, 3 times a day,the dose 0. 8 g of oxiracetam was taken 3 times a day and 2 Ginkgo Biloba Leaves Extract tablets was taken 3 times a day in the treatment group,period of treatment was 6 months. The curative effect was measured by using Montreal cognitive assessment scale (MoCA),Blessed-Roth dementia table,severity of clinical dementia rating scale (WMS) rating, respectively before treatment and on the 3th, 6th month after treatment,and monitored the adverse reactions. Results There were no statistically significant differences on the scores of MoCA, WMS and Blessed-Roth dementia table between treatment group and control group before treatment ( all P>0. 05 ) . The scores of MoCA, WMS in the treatment group and control group on 6 months after treatment were significantly higher than those before treatment and 3 months after treatment, and the scores of Blessed-Roth dementia table in the treatment group and control group on 6 months after treatment were significantly lower than those before treatment and 3 months after treatment ( P0. 05). Conclusion The curative effect of cocktail therapy is better than traditional remedies for treating patients with PDD, and it is high safety.
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OBJECTIVE:To observe the effects and safety of Congrong yishen granule combined with Donepezil hydrochloride tablet on mental state and quality of life in patients with Parkinson disease with dementia(PDD). METHODS:A total of 60 PDD patients were randomized into control group and treatment group,with 30 cases in each group. Both groups were given drugs for Parkinson disease. Control group was additionally given Donepezil hydrochloride tablet 5 mg,qd;treatment group was additionally given Congrong yishen granules 2 g,bid,on the basis of control group. The treatment lasted for 6 months in both groups. MMSE, MoCA,ADAS-Cog,ADL-R and TCM symptom score were observed in 2 groups before and after treatment. The occurrence of ADR were compared between 2 groups. RESULTS:Before treatment,there was no statistical significance in MMSE,MoCA, ADAS-Cog,ADL-R or TCM symptom score between 2 groups (P>0.05). After treatment,MMSE and MoCA score of 2 groups were increased significantly,while ADAS-Cog,ADL-R and TCM symptom score were decreased significantly;the treatment group were better than the control group,with statistical significance (P<0.05). No obvious ADR was found in 2 groups. CONCLU-SIONS:Congrong yishen granule combined with donepezil hydrochloride tablet can significantly improve mental state and cogni-tive ability of PDD patients,and relieve clinical symptoms with good safety.
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Dementia with Lewy bodies (DLB) is the second most common causes of dementia. It can exhibit a variety of clinical symptoms including cognitive decline, cognitive fluctuation, visual hallucinations, parkinsonism, REM sleep behavior disorder, hypersensitivity to neuroleptics and autonomic dysfunctions. Despite more well-known criteria for DLB, there are often misdiagnosis and inappropriate treatment. It gives a lot of clinical burden to the clinician as well as to patients and families. When reducing the misdiagnosis, the burden of all will be reduced. The special concern and solicitation are needed in order not to miss the diagnosis when the cardinal features of DLB may not be volunteered by patients and the caregivers. To control the symptoms, clinicians must find and reduce drugs that can have the negative effects on DLB symptoms. There is limited evidence about specific interventions but available data suggest cholinesterase inhibitors improve the cognitive and behavioral symptoms and menmantine slightly improves the global impression.