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)

Parkinson's disease (PD) is a chronic, neurodegenerative disease with degeneration of the central dopaminergic neurons in the substantia nigra, leading to a depletion of dopamine (DA) in the striatum. This depletion causes the clinical hallmarks of this disease: bradykinesia, hypokinesia, rigidity, tremor and postural instability. Besides these well known motor symptoms, non-motor symptoms may develop, such as hyposmia, sleep disorders, autonomic disturbances, depression, cognitive impairment and psychosis. Pathophysiological mechanisms underlying these symptoms not only comprise Lewy body pathology in the central dopaminergic system, but also in the noradrenergic, serotinergic and cholinergic transmittersystems. Indeed, in Parkinson's disease, about 30-40% of the patients suffers fluctuating psychotic symptoms, mainly paranoid delusions and/or visual or acoustic hallucinations, symptoms considered to represent major contributors to patient and caregiver distress and nursing home placement. Endogenous (related to the disease process itself) as well as exogenous (related to therapeutical interventions) psychotogenic factors may contribute to the development of psychotic symptoms in PD. Therapeutical strategies, therefore, are aimed to reduce both endogenous and exogenous factors. To reduce endogenous psychotogenic factors, cholinesterase inhibitors, suggested to reduce cognitive deterioration, now seem to be the drugs of choice. In exogenously induced psychotic symptoms, atypical antipsychotics are considered the most effective. However, as psychotic symptoms in PD are often influenced by both endogenous and exogenous factors, a combination of both strategies may be preferred.
 ...
PMID:PD-related psychosis: pathophysiology with therapeutical strategies. 1744 13

Dementia is increasingly recognized as a symptom associated with idiopathic Parkinson's disease, and is found in up to 40% of all patients suffering from that condition. Clinically, the diagnosis of Parkinson's dementia is characterized by executive deficits, which can be identified by neuropsychological tests. In the individual case, differentiating this from other forms of dementia with extrapyramidal motor symptoms can be very difficult. With regard to therapy, there is evidence that cholinesterase inhibitors may be effective.
 ...
PMID:[Parkinson's disease dementia]. 1761 43

Executive functions describe a variety of cognitive processes responsible for structuring behaviors around goals, and developing plans to achieve those goals in relation to the environment. In addition to deficits in basal forebrain cholinergic neuronal input into the frontal cortex, impaired control of executive function has been associated with lesions to the frontal cortex and its basal ganglia-thalamic connections. In addition to executive dysfunction, features that imply fronto-subcortical pathology include profound slowing of cognition, attentional deficits, apathy and changes in mood. Fronto-subcortical systems are vulnerable to white matter change, atrophy, and certain forms of neurotransmitter depletion. The diffuse, and likely non-cholinergic, projections of acetylcholinesterase (AChE)-containing thalamic neurons innervate all cortical areas. Butyrylcholinesterase (BuChE) activity is relatively high in thalamic nuclei that project to frontal cortical structures involved in attention, executive function, and behavior. However, the largest pool of BuChE in the brain is found in the glia, particularly those in deeper cortical and subcortical structures. These findings suggest that BuChE may also be an important therapeutic target in the management of symptoms due to subcortical pathology. Whereas 'pure' Alzheimer's disease (AD) may involve significant subcortical pathology in addition to cortical pathology, AD with cerebrovascular disease, vascular dementia (VaD), Parkinson's disease dementia (PDD) and dementia due to Lewy bodies (DLB) may involve a generally greater degree of subcortical, in addition to cortical, pathology. It may be hypothesized that these dementia types, which are characterized by executive dysfunction, might derive particular benefits from cholinesterase inhibitors such as rivastigmine that inhibit BuChE in addition to AChE.
 ...
PMID:Executive dyscontrol in dementia, with emphasis on subcortical pathology and the role of butyrylcholinesterase. 1762 85

I report here clinical effects of cholinesterase inhibitors (rivastigmine and donepezil) on visual hallucinations emerging in the course of Parkinson's disease (PD) and clinically unresponsive to antipsychotics. Five patients with PD (with or without dementia) complicated by visual hallucinations and unresponsive to atypical antipsychotics were offered a 12-week, open-label trial of a cholinesterase inhibitor. All 5 subjects completed the trial with no major adverse effects and, of note, no discontinuations due to adverse events. Visual hallucinations resolved in 4 subjects and were markedly diminished in one person. Neither changes in UPDRS scores nor exaggeration of subjective complaints about extrapyramidal symptoms were noted during treatment. Cholinesterase inhibitors might represent a useful alternative to antipsychotics for patients with PD accompanied by visual hallucinations even in the absence of dementia. One must, however, not forget that their use with this indication remains experimental and safety measures as well as accurate clinical surveillance are of crucial importance.
 ...
PMID:Parkinson's disease-related visual hallucinations unresponsive to atypical antipsychotics treated with cholinesterase inhibitors: a case series. 1762 23

Serial assessments of cognitive functioning in individuals with Parkinson's disease (PD) are commonly used for the detection of incident dementia and neurobehavioral changes associated with treatments using neuromodulation (e.g., deep brain stimulation) and pharmacological agents (e.g., cholinesterase inhibitors). This study provides test-retest stability, expected practice effects, and practice-corrected reliable change indices for several commonly used neuropsychological tests from 62 older adults with mostly mild PD who underwent repeat evaluations approximately 17 months apart. At the group level, results showed adequate test-retest reliability (Spearman's rho range=0.24-0.86) and generally small practice effects (Cohen's d range=0.00-0.50). Application of reliable change indices using 90% confidence intervals showed the expected number of individuals (generally 10% or fewer) with statistically meaningful improvements (range=0-12%) or declines (range=2-8%) in cognitive performance at retest. Limitations discussed include ceiling effects at test baseline, sample homogeneity, interpretative cautions, and generalizability of study results. These data may be useful to researchers and clinicians interested in determining the statistical significance of changes in cognitive test performance in persons with PD over a 1- to 2-year interval.
 ...
PMID:Assessing cognitive change in Parkinson's disease: development of practice effect-corrected reliable change indices. 1764 4

The dual cholinesterase inhibitor rivastigmine is approved in capsule form in many countries for the symptomatic treatment of dementia associated with Alzheimer disease (AD) and Parkinson disease (PD). All orally administered cholinesterase inhibitors are associated with central cholinergic gastrointestinal side effects, particularly during the titration phase, which are believed to be caused by a rapid increase in brain acetylcholine levels after effective inhibition of the target enzymes. A recently developed rivastigmine transdermal patch may have the potential to reduce such side effects. Pharmacokinetic studies have shown that transdermal administration of rivastigmine prolongs t(max), lowers C(max), and reduces fluctuations in plasma concentration. The 10-cm(2) rivastigmine patch provides comparable exposure (area under the curve, AUC) to the highest capsule dose (6-mg BID) and may be the target maintenance dose for most patients, delivering optimal rivastigmine exposure to produce a therapeutic effect. The potential of a patch to improve the tolerability of rivastigmine (e.g., nausea and vomiting) while permitting similar exposure to the highest doses of capsules may, in turn, lead to improved efficacy and compliance.
 ...
PMID:Pharmacokinetic rationale for the rivastigmine patch. 1764 18

Transdermal patches are used for the treatment of various diseases including neurologic and psychiatric disorders such as Parkinson disease (PD), major depression, and attention deficit hyperactivity disorder. They are believed to offer many advantages over conventional oral therapies. By providing smoother, continuous drug delivery and steadier plasma levels, patches may reduce the incidence of side effects, thus making optimal therapeutic doses easier to attain and potentially improving treatment efficacy and compliance. Drug delivery systems such as patches that are more patient- and caregiver-friendly may enable patients to continue treatment for longer periods and to attain greater, more sustained treatment benefits. To date, approved therapies for Alzheimer disease (AD), including cholinesterase inhibitors and memantine, are orally administered. Potential advantages associated with patches provide a therapeutic rationale to offer additional benefits in AD patients. Rivastigmine is well suited to patch administration because it is a small, potent molecule that is both lipophilic and hydrophilic. A rivastigmine patch has been developed and may provide a promising new approach to dementia therapy.
 ...
PMID:Rationale for transdermal drug administration in Alzheimer disease. 1764 21

In parkinsonian syndromes dementia frequently occurs in the disease progress. The cholinergic system has been proposed as playing a key role in cognitive disturbances. Therefore the application of cholinesterase inhibitors (ChEI) is also hotly argued for dementia associated with parkinsonian syndromes. This review focuses on the specific symptoms of dementia in Parkinson's disease (PDD), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). The effect of cholinergic treatment on cognition and behaviour is reported and critically discussed. There is evidence that medication with some ChEIs reduces cognitive disturbances and to a lesser extent improves activities of daily living in PDD. Behavioural symptoms also seem to be positively influenced by treatment with ChEIs in both PDD and DLB. The effect of treatment with cholinesterase inhibitors in PSP and CBD warrants more carefully designed studies including sufficient numbers of patients.
 ...
PMID:[Treatment for dementia in parkinsonian syndromes. Efficacy of cholinesterase inhibitors]. 1768 35

(1) Three cholinesterase inhibitors are marketed in France for the treatment of Alzheimer's disease: donepezil, galantamine and rivastigmine. Tremor and dystonia are known adverse effects of cholinesterase inhibitors. (2) In patients with Parkinson's disease who have cognitive disorders, or in patients with Lewy body dementia, exacerbations of parkinsonism and tremor have been observed during treatment with cholinesterase inhibitors at normal doses. The disorders were reversible on withdrawal of the cholinesterase inhibitor. (3) Withdrawal of cholinesterase inhibitors should be considered if gait disorders, falls or parkinsonism occur or worsen during treatment.
 ...
PMID:Cholinesterase inhibitors: tremor and exacerbation of Parkinson's disease. 1792 35

The authors review current literature on hallucinations in Parkinson's disease (PD). Recent neuropathological studies showed that hallucinations occur in synucleinopathies and are a significant predictor of Lewy Body depositions. Therefore, hallucinations are a hallmark of PD and of dementia with Lewy Bodies. Visual hallucinations are mostly complex and kinematic; preserved or disturbed insight on the nature of hallucinations is a major prognostic factor, although eventually all hallucinators will present with reduced insight. Current theories on the origin of hallucinations point to visual dysfunction, dream overflow and cognitive impairment, yet objection can be raised on each one of the putative models of hallucinations. Understanding of the origin of hallucinations is required in order to develop treatments: all treatment evaluations were focused in general on psychosis, and only clozapine obtained positive evidence-based ratings on efficacy. However, it is likely that cholinesterase inhibitors, antipsychotics and anti-5-hydroxytryptamine(3) agents and drugs acting on sleep regulation will have different and perhaps opposite effects on different types of hallucinations, whether they are accompanied by disturbed insight, sleep disorders or other psychotic features. Further studies will try to separate phenomenology and responses to treatment and will investigate the relevance of concomitant sleep disorders and abnormality of frontoparietal networks involved in the attention process.
 ...
PMID:New approaches to understanding hallucinations in Parkinson's disease: phenomenology and possible origins. 1805 66


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