Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0426980 (motor symptom)
 471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reliable and well-validated biomarkers for PD to identify individuals "at risk" before motor symptoms, accurately diagnose individuals at the threshold of clinical PD, and monitor PD progression throughout its course would dramatically accelerate research into both PD cause and therapeutics. Biomarkers offer the potential to provide a window onto disease mechanism, potentially generating therapeutic targets for disease. In particular, biomarkers enable investigation of the premotor period of PD before typical symptoms are manifest, but while degeneration has already begun. Given the multiple genetic causes 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 in PD onset and clinical progression, it is likely many biomarkers with a focus ranging from clinical symptoms to PD pathobiology to molecular genetic mechanisms will be necessary to fully map PD risk and progression. Biomarkers are also critical in new drug development for PD, both in early validation studies to assess drug dosing and to determine drug penetrance into the brain, and in later efficacy studies to complement PD clinical outcomes. During the past two decades, much progress has been made in identifying and assessing PD biomarkers, but as yet, no fully validated biomarker for PD is currently available. Nonetheless, there is increasing evidence that molecular genetics, focused -omic (proteomic, metabolomic, and transcriptomic) assessment of blood and cerebrospinal fluid, and advanced in vivo brain imaging will provide critical clues to assist in the diagnosis and medical management of PD patients.
 ...
PMID:Biomarkers for Parkinson's [corrected] disease: tools to assess Parkinson's disease onset and progression. 1912 87

Most patients with idiopathic PD (IPD) show variable degrees of cognitive decline. The purpose of this study was to evaluate the relationship between the predominant motor symptom at the time of disease onset and the level of cognitive function in patients with IPD. A total of 159 patients with IPD were enrolled in this study. The patients' initial motor symptoms were classified into three types: tremor-dominant (TD), bradykinesia and rigidity-dominant (BRD), gait and postural instability-dominant (GPD). Disease severity was rated according to the Hoehn-Yahr classification (H&Y stage). Overall cognitive status was evaluated using the Korean versions of the Mini-Mental State Examination (K-MMSE) and the Modified Mini-Mental State (3MS) tests. The GPD group showed the lowest scores of the K-MMSE/3MS, and the patients with TD showed the best performance in the cognitive analysis (p<0.05). The patients who were older at disease onset showed worse cognitive performance than those the patients who were younger at disease onset (p<0.05). There was no difference in cognitive status according to H&Y stages. The accurate classification of initial motor symptoms and the detailed history, including the exact onset age of IPD, may allow us to predict cognitive decline in IPD.
 ...
PMID:Relationship between clinical phenotypes and cognitive impairment in Parkinson's disease (PD). 1913 59

About one fourth of Lewy body disease (LBD) patients show cortical beta-amyloid load, basically a hallmark of Alzheimer disease (AD). Using [11C]PIB-PET, we tested whether LBD patients with beta-amyloid burden differ from those without with respect to demographic, clinical, biochemical and genetic parameters. Thirty-five LBD subjects (9 patients with Lewy body dementia, DLB; 12 demented Parkinson patients, PDD; 14 non-demented PD, PDND) underwent [11C]PIB-PET, and were classified as either PIB(+) or PIB(-) according to cortical PIB uptake. PIB+ and PIB(-) patients were then compared according to demographic, clinical, biochemical and genetic parameters. None of the PDND, but four PDD and four DLB subjects were PIB+. In PIB+ subjects, ApoE4 prevalence was higher, CSF Abeta42 levels were lower and, among demented patients, PIB-binding was associated with a lower MMSE score. Motor symptoms were not associated with PIB binding. Thus, LBD patients with cortical beta-amyloid show characteristics usually observed in AD.
 ...
PMID:Cortical PIB binding in Lewy body disease is associated with Alzheimer-like characteristics. 1916 86

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

Motor symptoms in Parkinson's disease (PD) are associated with complex changes of firing properties in basal ganglia output neurons (BGON). The abnormalities are generally attributed to altered synaptic input and potential post-synaptic mechanisms are currently unknown. Our cell-type selective transcriptome analyses of BGON in the rat 6-hydroxydopamine (6-OHDA) model of PD identified the ion channel HCN3 as a likely contributor to altered neuronal excitability. Quantitative PCR experiments confirmed the HCN3 upregulation in the rat and mouse 6-OHDA models and also demonstrated selectivity of the effect for HCN3. In accordance with the mRNA expression data, in vitro whole cell patch-clamp recordings in BGON showed increased HCN3 current amplitudes and increased rebound excitability in BGON of 6-OHDA treated rats. These data establish HCN3 up-regulation as a novel candidate mechanism that might contribute to the in vivo changes of electrical activity in basal ganglia output neurons of the parkinsonian brain.
 ...
PMID:Dopamine depletion induced up-regulation of HCN3 enhances rebound excitability of basal ganglia output neurons. 1932 57

More therapeutic options have become available for Parkinson's disease (PD) in recent years, leading to significant improvements in motor control both at early and advanced disease stages. More importantly, the need to expand disease management beyond motor symptom control has been recently highlighted and contribution of non-motor features to quality of life is now relevant. Dopamine agonists represent a valid therapeutic option in PD and their effect on non-motor domains like mood or cognition is now acknowledged as a key factor in fully addressing patients' needs. Pramipexole is a well established dopamine agonist that is currently being investigated for its potential disease-modifying effect and action on mood in PD. In this review we will examine factors contributing to treatment decision-making and discuss how a proper balance between motor and non-motor features should be aimed for in approaching PD therapy.
 ...
PMID:Dopamine agonist-based strategies in the treatment of Parkinson's disease. 1938 65

Gastrointestinal (GI) dysfunction is the most common non-motor symptom of Parkinson's disease (PD). Symptoms of GI dysmotility in PD include early satiety and weight loss from delayed gastric emptying and constipation from impaired colonic transit. Understanding the pathophysiology and treatment of these symptoms in PD patients has been hampered by the lack of investigation into GI symptoms and pathology in PD animal models. We report that the parkinsonian neurotoxin and mitochondrial complex I inhibitor rotenone causes delayed gastric emptying and enteric neuronal dysfunction when administered chronically to rats in the absence of major motor dysfunction or CNS pathology. When examined 22-28 days after initiation of rotenone infusion by osmotic minipump (3 mg/kg/day), 45% of rotenone-treated rats had a profound delay in gastric emptying. Electrophysiological recording of neurally-mediated muscle contraction in isolated colon from rotenone-treated animals confirmed an enteric inhibitory defect associated with rotenone treatment. Rotenone also induced a transient decrease in stool frequency that was associated with weight loss and decreased food and water intake. Pathologically, no alterations in enteric neuron numbers or morphology were apparent in rotenone-treated animals. These results suggest that enteric inhibitory neurons may be particularly vulnerable to the effects of mitochondrial inhibition by parkinsonian neurotoxins and provide evidence that parkinsonian gastrointestinal abnormalities can be modeled in rodents.
 ...
PMID:Delayed gastric emptying and enteric nervous system dysfunction in the rotenone model of Parkinson's disease. 1940 96


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