Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prior to the onset of the cardinal motor features of idiopathic Parkinson's disease (PD), other manifestations of neurodegeneration such as olfactory dysfunction are often apparent. Characterizing these potential biomarkers of preclinical PD is particularly important in identifying individuals who will go on to develop disabling symptoms, and thus be good candidates for new neuroprotective strategies. As shown by the Braak neuropathologic staging of PD, the olfactory system is among the first neuronal populations to display Lewy body pathology. Clinically, loss of smell can be easily tested in the office using several validated techniques and is often helpful to the physician in distinguishing idiopathic PD from other forms of parkinsonism. Recent findings have indicated that a decline in olfaction may be observed in selected at-risk patients, which has significant implications for identifying potential study populations. Ongoing studies of olfactory dysfunction may also reveal potential for use as a medication-independent biomarker of disease progression in addition to use as a biomarker for the diagnosis of PD.
 ...
PMID:Olfactory dysfunction in Parkinson's disease. 1809 58

Parkinson's disease (PD) is a neurodegenerative disorder involving several neuronal systems. Impaired olfactory function may constitute one of the earliest symptoms of PD. However, it is still unclear to what degree changes of the olfactory epithelium may contribute to dysosmia and if these changes are different from those of other hyposmic or anosmic patients. This study aimed to investigate the hypothesis that olfactory loss in PD is a consequence of specific PD-related damage of olfactory epithelium. Biopsies of 7 patients diagnosed with PD were taken. Six patients with PD were hyposmic, one anosmic. As non-PD controls served 9 patients with hyposmia, 9 with anosmia, and 7 normosmic individuals. Further, nasal mucosa of 4 postmortem individuals was investigated. Immunohistochemical examinations were performed with antibodies against olfactory marker protein (OMP), protein gene product 9.5 (PGP 9.5), beta-tubulin, (BT), proliferation-associated antigen (Ki 67), the stem cell marker nestin, cytokeratin, p75NGFr, and alpha-synuclein. Most of the biopsy specimens exhibited irregular areas of olfactory-like, dysplastic epithelium positive for either PGP 9.5 or BT, but negative for OMP. No major histochemical differences in either the expression or distribution of these proteins were observed in the olfactory epithelium of patients with PD compared with controls. Reverse transcription PCR (RT-PCR) data indicated mRNA for OMP in almost all subjects, independently of their olfactory performance. These data support the idea that olfactory loss in Parkinson's disease is not a consequence of damage to the olfactory epithelium but rather results from distinct central-nervous abnormalities.
 ...
PMID:Biopsies of olfactory epithelium in patients with Parkinson's disease. 1920 70

The proteinopathy sporadic Parkinson's disease (sPD) is the second most frequent degenerative disorder of the human nervous system after Alzheimer's disease. The alpha-synuclein inclusion body pathology (Lewy pathology) associated with sPD is distributed throughout the central, peripheral, and enteric nervous systems. The resulting nonrandom neuronal dysfunction and, in some regions, neuronal loss is reflected in a topographic distribution pattern of the Lewy pathology that, in the brain, can be staged. Except for olfactory structures and spinal cord constituents of the pain system, sensory components of the nervous system remain uninvolved or virtually intact. The most disease-related damage revolves around motor areas--particularly around superordinate centers of the limbic and visceromotor systems as well as portions of the somatomotor system. Vulnerable regions are interconnected anatomically and susceptible nerve cell types are not neurotransmitter-dependent. Not all clinical symptoms emerging in the course of sPD can be explained by a lack of dopamine in the nigrostriatal system. These include autonomic dysfunction, pain, hyposmia or anosmia, excessive daytime sleepiness, rapid eye movement (REM) sleep behavioral disorder, depression, anxiety, cognitive decline, and dementia. Against the background of the normal morphology and anatomy, the authors analyze the pathoanatomy of sPD in the nervous system at various neuropathological stages and summarize the potential functional consequences of the lesions.
 ...
PMID:Neuroanatomy and pathology of sporadic Parkinson's disease. 1923 May 52

We compared the relationship between regional cerebral blood flow (rCBF) of the olfactory area and the cognitive function and anosmia in patient with Parkinson disease (PD) and in those with Alzheimer disease (AD). UPDRS III, MMSE, HDS-R, CDR, Beck Depression Inventory (BDI) were employed in this study. The subjects included 56 PD patients (average age 71.4+/-9.69 years), 23 AD patients (average age 73.3+/-7.12 years), 12 patients with mild cognitive impairment (MCI) (average age 72.5+/-6.89 years), and 9 age-matched controls (NC) (average age 73.8+/-6.61 years). Next we intravenously injected 1 ampule of thiamine propyldisulphide (Alinamin) and confirmed anosmia. In addition, we performed 123I-IMP SPECT (SEE methods) and satistically determined rCBF of the olfactory area based on the basis of the Z scores of the interest area. Anosima was detected in approximately 40% of the PD and AD patients. The HDS-R and MMSE scores were significantly higher in patients with anosima than in those without anosima; the CDR scores were significantly higher in the former than in the latter. Further, the incidence of anosima in PD patients and AD patients with MCI increased with an increase in the CDR scores. In order to determine the rCBF of the olfactory area of the PD and AD patients. As to rCBF of the olfactory area, we examined left and right Z scores of hippocampus, parahippocampus, amygdala, and uncus at Talairach level 3 and the scores of the Brodmann area 28, 34, 35, and 36 at Talairach level 5. In patients with anosmia, the Z scores were significantly high in cases with anosmia in all areas except the right Brodmann area 34 in PD patients and the right Brodmann area 28 and bilateral the Brodmann area 34 of both sides in AD patients. Some parts of the olfactory area are closely related to cognitive function, and it appeares that a reduced rCBF in the olfactory areas may lead to a functional decline in these regions which may cause anosmia and cognitive decline in PD and AD patients.
 ...
PMID:[Relationship between the regional cerebral blood flow and the cognitive function and anosmia in patients with Parkinson disease and Alzheimer disease]. 1952 36

Parkinson's disease (PD) is a progressive neurodegenerative disorder that is characterized by the loss of dopamine neurons in the substantia nigra pars compacta, culminating in severe motor symptoms, including resting tremor, rigidity, bradykinesia, and postural instability. In addition to motor deficits, there are a variety of nonmotor symptoms associated with PD. These symptoms generally precede the onset of motor symptoms, sometimes by years, and include anosmia, problems with gastrointestinal motility, sleep disturbances, sympathetic denervation, anxiety, and depression. Previously, we have shown that mice with a 95% genetic reduction in vesicular monoamine transporter expression (VMAT2-deficient, VMAT2 LO) display progressive loss of striatal dopamine, L-DOPA-responsive motor deficits, alpha-synuclein accumulation, and nigral dopaminergic cell loss. We hypothesized that since these animals exhibit deficits in other monoamine systems (norepinephrine and serotonin), which are known to regulate some of these behaviors, the VMAT2-deficient mice may display some of the nonmotor symptoms associated with PD. Here we report that the VMAT2-deficient mice demonstrate progressive deficits in olfactory discrimination, delayed gastric emptying, altered sleep latency, anxiety-like behavior, and age-dependent depressive behavior. These results suggest that the VMAT2-deficient mice may be a useful model of the nonmotor symptoms of PD. Furthermore, monoamine dysfunction may contribute to many of the nonmotor symptoms of PD, and interventions aimed at restoring monoamine function may be beneficial in treating the disease.
 ...
PMID:Nonmotor symptoms of Parkinson's disease revealed in an animal model with reduced monoamine storage capacity. 1982 98

Hyposmia is a common nonmotor feature of Parkinson's disease (PD) and has been variably detected in monogenic Parkinsonisms. To assess olfactory dysfunction in PINK1-related Parkinsonism, we evaluated olfactory detection threshold, odor discrimination, and odor identification in five groups of subjects: sporadic PD (n = 19), PINK1 homozygous (n = 7), and heterozygous (n = 6) parkinsonian patients, asymptomatic PINK1 heterozygous carriers (n = 12), and Italian healthy subjects (n = 67). All affected subjects and all healthy heterozygotes but one resulted hyposmic, with most patients in the range of functional anosmia or severe hyposmia. Detection threshold was more preserved and discrimination more impaired in patients with PINK1 mutations than in PD cases. Alterations of detection and discrimination were observed also in PINK1 asymptomatic heterozygotes. On the contrary, odor identification appeared to be mostly related to the disease status, as it was impaired in nearly all patients (including PD and PINK1 cases) and preserved in healthy heterozygotes. Our data indicate that olfactory dysfunction is common in PINK1 Parkinsonism and consists typically in defective odor identification and discrimination. A milder olfactory deficit, mostly involving discrimination, can be found in asymptomatic heterozygotes, possibly indicating an underlying preclinical neurodegenerative process.
 ...
PMID:Olfactory dysfunction in Parkinsonism caused by PINK1 mutations. 1989 Sep 73

Olfactory and gustatory disorders increase with advancing age. Moreover, olfactory disorders are common in neurodegenerative disorders, especially in idiopathic Parkinson's disease (IPD) and Alzheimer's Disease (AD). Since the decrease in olfactory function is usually gradual, it often remains undetected. Given the poor self-assessment of olfactory function, olfactory testing is mandatory in suspected cases to establish the diagnosis of hyposmia or anosmia. The high rate of anosmia over the age of 70 is suspected to be due to several factors such as changes in the olfactory epithelium (reduced mucus secretion, hormonal changes, changes in epithelial thickness, for example), and the reduced neuroregeneration rate in olfactory receptor cells themselves. There is no known adequate treatment for stopping or reversing this age-related decline in olfaction. In IPD, olfactory impairment precedes motor symptoms by years and is independent of dopaminergic loss. Using fMRI, altered neuronal activity in the amygdaloid complex and hippocampal formation during olfactory stimulation have been demonstrated, as has a link between the expression of olfactory event-related potentials and olfactory-induced brain activity. In AD--by contrast with IPD--the severity of the disease and the olfactory disorder correlate. The olfactory disorders alone, however, cannot distinguish between AD and IPD. A complete loss of gustatory function is rare, while dysgeusia is common, especially with increasing age. There are multiple possible explanations, including concomitant disease and the side-effects of medication. These need to be established on the basis of exact history and examination. Treatment remains difficult.
 ...
PMID:Ageing, neurodegeneration, and olfactory and gustatory loss. 2008 14

Autonomic symptomatology is prevalent in Parkinson's disease (PD) and impacts quality of life, yet little data exist on the presentation of autonomic dysregulation. This study measures orthostasis, constipation, and anosmia in 58 PD patients and 51 age-matched controls enrolled in the University of Florida's Movement Disorders Center. Patients had their blood pressure measured while seated and in standing position, performed the University of Pennsylvania Smell Identification Test (UPSIT), and completed a constipation survey. Our PD patients had a significantly different average decrease in systolic BP from a seated to standing position compared with their age-matched controls (5.90 mmHg (SD 17.03) vs. 2.6 mmHg (SD 11.28); p = .05). The difference in heart rate from seated to standing positions was not significant. Reflexive tachycardia was inversely proportional to levodopa equivalent daily dose (LEDD) score (p = .002). Anosmia occurred in 96.4% of the PD group and 49% of the controls (p < .001). Constipation was also more prevalent in the PD population than in the controls (67.3% vs. 21.6%; p < .001). Both anosmia and constipation were correlated with disease duration (p = .038 and .04 respectively). Our study suggests that increasing levels of dopaminergic therapy inhibits reflexive tachycardia. Furthermore, our study suggests that anosmia and constipation progress with the primary disease process.
 ...
PMID:The relationship between anosmia, constipation, and orthostasis and Parkinson's disease duration: results of a pilot study. 2012 74

The aim of the study was to explore the prevalence and differences of nonmotor symptoms (NMSs) in patients with young-onset Parkinson's disease (YOPD) with and without mutations in the Parkin gene and late-onset Parkinson's disease (LOPD). Twenty-seven patients with YOPD and 27 with LOPD, as well as 16 patients with homozygous or compound heterozygote Parkin mutations filled in the nonmotor symptoms questionnaire, a 30-item self-completed questionnaire that addresses various NMSs. Overall, NMSs were more prevalent in YOPD (12.07 +/- 3.9; P = 0.009) and LOPD (13.26 +/- 5.8; P = 0.001) compared with Parkin mutation carriers (7.38 +/- 4.2). Dribbling of saliva, vivid dreams, loss of smell, and urinary urgency were more prevalent in YOPD compared with Parkin mutation carriers. Only anxiety was more prevalent in the latter. Apart from anxiety, NMSs appear to be less prevalent in Parkin gene-related parkinsonism. Although these results need further study, the presented data might be helpful in the clinical recognition of specific phenotypes and genotypes in YOPD. The data are in keeping with a different pathological disease process in Parkin gene-related parkinsonism.
 ...
PMID:Nonmotor symptoms in Parkin gene-related parkinsonism. 2062 19

Patients suffering from Parkinson's disease (PD) will typically experience a range of motor and nonmotor symptoms during the course of their illness, each of which will affect a particular individual to varying degrees. However, patients' perceptions of troublesome symptoms often differ from the clinician's view, and these discrepancies can hamper effective management of PD. In this study, we have assessed 265 consecutive PD patients by asking them to rank their three most troublesome symptoms in the last 6 months, so to gain further insight from the impact of illness on patients' quality of life. Patients were divided into early (<6 years) and late PD groups (>/=6 years) from symptom onset. The division at 6 years was based on the mean time from symptom onset to the development of motor complications. In the early PD group, the 5 most prevalent complaints (ranked in descending order) are slowness, tremor, stiffness, pain, and loss of smell and/or taste. In the advanced PD group, fluctuating response to their medication (most common: wearing-off phenomenon followed by dyskinesia), mood changes, drooling, sleep problems (most common: middle and late night insomnia followed by daytime sleepiness), and tremor were the top 5. Our findings provide further evidence for the diversity of experience in PD and suggest that as the disease advances the most troublesome issues that patients perceive are the lack of response to medication and the nonmotor aspects of the disease, highlighting the importance of assessment and patient-centered management in the follow-up of these patients.
 ...
PMID:Parkinson's disease symptoms: the patient's perspective. 2062 64


<< Previous 1 2 3 4 5 6 Next >>