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)

Our objective was to understand the impact of motor and nonmotor symptoms of patients with early and middle stage Parkinson's disease (PD) on their spouses' caregiver strain and depression. A sample of 219 spouse caregivers of PD patients participating in a clinical trial was evaluated for six dimensions of caregiver strain and depression using the Family Care Inventory. Motor and nonmotor (i.e., psychological) clinical symptoms collected from PD patients as part of the clinical trial protocol were used as predictors. Seven hierarchical regression analyses were used to determine the contribution of the motor and nonmotor clinical symptoms in explaining variation in each of the seven caregiver-dependent variables. Clinical symptoms explained 9-16% of the variance in caregiver strain and 10% of depression. Motor symptoms explained 0-6% of the variance and nonmotor psychological symptoms explained 7-13% of the variance in caregiver strain. Comparing our findings with literature that is deemed clinically relevant for patient symptoms that predict caregiver strain, we concluded that PD patient symptoms are important predictors of caregiver strain and depression. Patient nonmotor psychological symptoms have a much greater impact on caregiver strain and depression than patient motor symptoms.
 ...
PMID:Do motor and nonmotor symptoms in PD patients predict caregiver strain and depression? 1852 98

A potent 5-hydroxytryptamine (5-HT)2A receptor inverse agonist and antagonist, ACP-103 [N-(4-fluorophenylmethyl)-N-(1-methylpiperidin-4-yl)-N'-(4-(2-methylpropyloxy)phenylmethyl) carbamide (2R,3R)-dihydroxybutanedioate (2:1, active:salt)], was evaluated for its ability to reduce the primary motor symptom of tremor using tacrine-induced tremulous jaw movements in rats, which is an animal model of parkinsonian tremor. Furthermore, ACP-103 was evaluated for its ability to reduce levodopa-induced dyskinesias in monkeys rendered parkinsonian with MPTP [1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine]. ACP-103 reduced tacrine-induced tremulous jaw movements in rats. In addition, ACP-103 administered in combination with levodopa caused a dose-related reduction in dyskinesias in monkeys. These data suggest that ACP-103 may have the potential to reduce tremor and levodopa-induced dyskinesias in Parkinson's disease.
 ...
PMID:A 5-HT2A receptor inverse agonist, ACP-103, reduces tremor in a rat model and levodopa-induced dyskinesias in a monkey model. 1853 70

Genital dysfunction and testosterone deficiency occur frequently in Parkinson's disease and represent a typical non-motor symptom of the disorder. Despite that, to our knowledge no study investigated whether at experimental level this can be reproduced with classic Parkinsonism-inducing neurotoxins. In this study we evaluated the effects produced in the testis following administration of the Parkinsonism-inducing neurotoxin 1-methyl, 4-phenyl, 1,2,3,6-tetrahydropyridine in mice. At 7 days following treatment, in the presence of a severe nigrostriatal dopamine depletion, we found a marked decrease in testosterone plasma levels in 1-methyl, 4-phenyl, 1,2,3,6-tetrahydropyridine-treated mice. Such testosterone loss occurred concomitantly with loss of Leydig cells and the presence of altered morphology in the interstitium with severe mitochondrial degeneration in spared Leydig cells. The loss of Leydig cells was accompanied by a marked decrease in TH immunohistochemistry and TH protein in the interstitium. This was accompanied by a significant decrease in norepinephrine levels in the testis. These effects shed novel light to understand genital dysfunction and testosterone deficiency in Parkinsonism, while offering a new experimental model to reproduce genital dysfunction in Parkinson's disease.
 ...
PMID:MPTP-induced Parkinsonism is associated with damage to Leydig cells and testosterone loss. 1864 55

Levodopa has been the mainstay of symptomatic therapy for Parkinson Disease (PD) for 40 years providing benefit to virtually all patients. Levodopa therapy results in improved activities of daily living, enhanced quality of life, and improved mortality. However, the long-term use of levodopa is associated with the development of motor fluctuations and dyskinesia. In addition, levodopa therapy has further limitations. It has little or no effect on certain motor features (e.g. gait and balance dysfunction) and a non-motor symptom complex (autonomic dysfunction, pain syndromes, sleep disorders, mood disturbances, dementia). Further, multiple case reports illustrate the potential of levodopa and other dopaminergic agents to cause or reveal a series of impulse control disorders. This review highlights the levodopa unresponsive symptoms in PD.
 ...
PMID:Levodopa unresponsive symptoms in Parkinson disease. 1878 79

Spatial navigation is a complex process requiring integration of visuoperceptual information. The present study examined how visuospatial function relates to navigational veering in Parkinson's disease, a movement disorder in which visuospatial cognition is affected by the degeneration of the basal ganglia and resulting dysfunction of the parietal lobes. We hypothesized that patients whose initial motor symptoms start on the left versus right side of the body (LPD, predominant right-hemisphere dysfunction; RPD, predominant left-hemisphere dysfunction) would display distinct patterns of navigational veering associated with the groups' dissimilar visuospatial profiles. Of particular interest was to examine the association of navigational veering (lateral deviation along the medio-lateral axis) with perception of egocentric coordinates and of radial optic flow patterns, both of which are mediated by the parietal lobes. Thirty-one non-demented Parkinson's disease patients (16 LPD, 15 RPD) and 18 healthy control (HC) adults received visuospatial tests, of whom 23 Parkinson's disease patients and 17 HC also underwent veering assessment. The participants were examined on three visual-feedback navigation conditions: none (eyes closed), natural, and optic flow supplied by a virtual-reality headset. All groups veered to the left when walking with eyes closed, women with Parkinson's disease more so than the other participants. On the navigation assessments with visual feedback, only LPD patients deviated right of centre. On tests of visuospatial function, the perceived midline was shifted rightward in LPD (men and women), increasingly so with the addition of visual input. In contrast, men with RPD showed leftward deviation. RPD patients and HC perceived optic flow in the left hemifield as faster than in the right hemifield, with a trend for the opposite pattern for LPD. Navigational veering in LPD was associated with deviation of the perceived egocentric midline and not with perception of optic flow speed asymmetries, and in RPD it was also associated with visual dependence, though in fact LPD subjects were more visually dependent than those with RPD. Our results indicate that (i) parietal-mediated perception of visual space is affected in Parkinson's disease, with both side of motor symptom onset and gender affecting spatial performance, and (ii) visual input affects veering.
 ...
PMID:Impact of optic flow perception and egocentric coordinates on veering in Parkinson's disease. 1895 54

Non-motor symptoms, such as psychiatric symptoms and autonomic dysfunction, are common co-morbid conditions in Parkinson's disease (PD) and major contributors to poor quality of life and disability. Within the group of neuropsychiatric conditions, depressive symptoms are the most common condition. Despite their frequency and importance, depressive symptoms can be difficult to assess and diagnose and thus depression in PD is frequently unrealized. Diagnostic challenges include the overlap of depressive symptoms with motor and non-motor symptoms of PD, such as dementia and apathy. Furthermore, there are no definite standards to assess and diagnose depression in PD leading also to the lack of exact data on the epidemiology of this non-motor symptom in PD. Depending on the diagnostic test and the study design the prevalence of depression in PD is reported between 7 and 72% of PD patients with approximately 40% in most cross-sectional studies. In contrast, the pathogenesis and long-term course of depression in PD remain elusive. Current hypothesis, however, includes that depressive symptoms are part of the core condition of PD when regarded as an entity. The present review summarizes the current knowledge on epidemiology, pathogenesis and diagnosis of depression in PD and proposes on this data base a standard procedure for screening and diagnosis of depressive symptoms in PD.
 ...
PMID:[Depression in Parkinson's disease. Part 1: epidemiology, signs and symptoms, pathophysiology and diagnosis]. 1901 23

The role of corticostriatal circuits in hierarchical pattern perception was examined in Parkinson's disease. The hypothesis was tested that patients with right-side onset of motor symptoms (RPD, left hemisphere dysfunction) would be impaired at local level processing because the left posterior temporoparietal junction (TP) emphasizes processing of local information. By contrast, left-side onset patients (LPD; right hemisphere dysfunction) would show impaired global processing because right TP emphasizes global processing. Participants identified targets at local or global levels without and with attention biased toward those levels. Despite normal attentional control between levels, LPD patients showed a single dissociation, demonstrating abnormal global level processing under all conditions, whereas RPD patients showed abnormal local level processing mainly when attention was biased toward the local level. These findings link side of motor symptom onset to visuospatial cognitive abilities that depend upon the contralateral TP, highlighting that side of onset can predict visuospatial impairments, and provide evidence that an inferior parietal-basal ganglia pathway involving the caudate head and the hemispherically asymmetrical TP region is necessary for hierarchical pattern perception.
 ...
PMID:Role of a lateralized parietal-basal ganglia circuit in hierarchical pattern perception: evidence from Parkinson's disease. 1917 Apr 37

The management of early Parkinson's disease (PD) involves the treatment of motor symptoms and, increasingly, non-motor symptoms. Given the fast pace of clinical research in PD, clinicians are faced with the challenge of integrating the latest findings into the ongoing care of individual PD patients. Part 1 of this 2-part article reviews motor symptom efficacy data for the newest PD treatment options, as well as for established therapies. Safety and tolerability data are also reviewed. Part 2 of the article reviews key findings relevant to the assessment of potential neuroprotective therapies and the treatment of non-motor symptoms.
 ...
PMID:Treatment of early Parkinson's disease. Part 1. 1917 60

Pathology and imaging studies have shown that patients with Parkinson disease (PD) have a prolonged period of uncertain duration when vulnerable neuronal populations are degenerating, but typical motor symptoms have not yet developed. This provides both an opportunity-it may be best to test new medications and, ultimately, treat PD patients during this early phase of disease--and a challenge--how to find these premotor PD subjects? Imaging biomarkers targeting the premotor period are critical to elucidate both the onset and progression of premotor PD. Widespread data have demonstrated that dopaminergic imaging can detect PD subjects at the motor symptom threshold. Novel strategies combining dopaminergic imaging with known genetic mutations for PD or early clinical signs and PD-associated symptoms, such as olfactory loss and sleep disturbances like REM behavior disorder, have begun to be used to identify individuals at risk for PD before motor symptoms become manifest. Early studies also have used imaging targeting norepinephrine, serotonin, cholinergic, or other neuronal systems to focus on early cardiac, cognitive, and behavioral symptoms. Imaging of nondopaminergic targets such as inflammation or alpha-synuclein deposition may provide further insight into the etiology of PD. Given the multiple genetic etiologies for PD already identified, the marked variability in the loss of dopaminergic markers measured by imaging at motor symptom onset, and the clear heterogeneity of clinical symptoms at PD onset, it is certain that many imaging biomarkers with a focus ranging from clinical symptoms to PD pathobiology to molecular genetic mechanisms, will be necessary to fully map PD risk.
 ...
PMID:Can we image premotor Parkinson disease? 1922 10

Sleep disorders are common in Parkinson's disease (PD) and have profound negative influences on quality of life. Sleep structure in healthy participants can be changed by repetitive transcranial magnetic stimulation (rTMS), but this has never been studied systematically in PD. Therefore, we characterized sleep in PD patients and examined effects of rTMS using a combination of actigraphy and a pressure sensitive pad. Thirteen PD patients received 5 Hz rTMS over the motor or parietal cortex. Actigraphic sleep estimates were obtained before, during and after rTMS, as well as compared with 8 healthy, age-matched controls. Motor symptoms and mood were evaluated before and after rTMS. Mixed-model regression analyses indicated that PD patients slept shorter (350 +/- 17 vs. 419 +/- 24 min., P = 0.02), more fragmented (fragmentation index 41 +/- 4 vs. 22 +/- 2, P = 0.0004) and had a lower sleep efficiency (77 +/- 2 vs. 86 +/- 2%, P = 0.002) and longer nocturnal awakenings (3.4 +/- 0.2 vs. 2.3 +/- 0.2 min., P = 0.003) than healthy controls. rTMS over the parietal, but not over the motor cortex improved sleep fragmentation (P = 0.0002) and sleep efficiency (P = 0.0002) and reduced the average duration of nocturnal awakenings (P = 0.02). No change of motor symptoms or mood was observed. Disturbed sleep in PD patients may partly be reversed by parietal rTMS, without affecting motor symptoms or mood.
 ...
PMID:Beneficial effect of transcranial magnetic stimulation on sleep in Parkinson's disease. 1922 4


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>