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

Dopamine depletion is involved in the pathophysiology of Parkinson's disease, whereas hyperdopaminergia may play a fundamental role in generating endophenotypes associated with schizophrenia. Sleep disturbances are known to occur in both schizophrenia and Parkinson's disease, suggesting that dopamine plays a role in regulating the sleep-wake cycle. Here, we show that novelty-exposed hyperdopaminergic mice enter a novel awake state characterized by spectral patterns of hippocampal local field potentials that resemble electrophysiological activity observed during rapid-eye-movement (REM) sleep. Treatment with haloperidol, a D2 dopamine receptor antagonist, reduces this abnormal intrusion of REM-like activity during wakefulness. Conversely, mice acutely depleted of dopamine enter a different novel awake state characterized by spectral patterns of hippocampal local field potentials that resemble electrophysiological activity observed during slow-wave sleep (SWS). This dopamine-depleted state is marked by an apparent suppression of SWS and a complete suppression of REM sleep. Treatment with D2 (but not D1) dopamine receptor agonists recovers REM sleep in these mice. Altogether, these results indicate that dopamine regulates the generation of sleep-wake states. We propose that psychosis and the sleep disturbances experienced by Parkinsonian patients result from dopamine-mediated disturbances of REM sleep.
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PMID:Dopaminergic control of sleep-wake states. 1703 44

(1) The restless legs syndrome consists of unpleasant sensory and motor symptoms of varying intensity in the lower limbs. Symptoms occur at rest, seated or lying down, are more intense in the evening and at night, and are relieved by moving the limb. This syndrome does not cause serious physical complications. When sleep disturbances occur, non drug methods should be tried first. (2) Ropinirole is a dopaminergic agonist initially marketed for the treatment of Parkinson's disease. It is the first drug to be approved for restless legs syndrome in France. (3) Three double-blind randomised placebo-controlled trials with similar designs showed minimal differences on a composite rating scale. After 12 weeks of treatment, ropinirole led to an improvement of about 3 points on a 40-point scale compared with placebo. (4) A 12-week double-blind randomised controlled trial and including patients who had "responded" to ropinirole showed a lower relapse rate in the group that continued to use ropinirole (32.6%) instead of switching to placebo (57.8%). However, we do not know if this was because of continued drug efficacy or a rebound effect in the placebo group. (5) The adverse effects of ropinirole in patients with restless legs syndrome had already been observed in the treatment of Parkinson's disease, and included nausea, vomiting, drowsiness, a sudden urge to sleep, syncope, hypotension, and hallucinations. (6) An increase in the severity of restless legs symptoms, typically seen with levodopa, was not evaluated in clinical trials of ropinirole. Some cases have nevertheless been reported. They describe the appearance of symptoms increasingly early in the evening, then in the afternoon, or as a rebound effect in the morning or the latter part of the night. Their intensity increases and can affect other parts of the body. (7) In practice, ropinirole has a negative risk-benefit balance in restless legs syndrome, which is a minor health disorder.
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PMID:Ropinirole: new indication. Restless legs: disproportionate adverse effects. 1712 23

Synucleinopathies, with and without dementia, encompass a wide range of diseases including Parkinson's disease, multiple system atrophy, rapid eye movement (REM) sleep behavior disorder, and dementia with Lewy bodies (DLB). DLB is a neurodegenerative disorder resulting in slowly progressive and unrelenting dementia until death. Prevalence studies suggest that it is the second most common dementing illness in the elderly. The neuropathologic findings of DLB show a wide anatomic range. Lewy bodies and Lewy-related pathology are found from the brain stem to the cortex and, in many cases, associated with concurrent Alzheimer's disease pathology. A recent international consortium on DLB has resulted in revised criteria for the clinical and pathological diagnosis of DLB incorporating new information about the core clinical features and improved methods for their assessment. The presentation of DLB is typically one of cortical and subcortical cognitive impairments, with worse visuospatial and executive dysfunction than Alzheimer's disease. There may be relative sparing of memory especially in the early stages. Core clinical features of DLB include fluctuating attention, recurrent visual hallucinations, and parkinsonism. Suggestive features include REM sleep behavior disorder, severe neuroleptic sensitivity, and low dopamine transporter uptake in the basal ganglia on functional neuroimaging. Additional supportive features that commonly occur in DLB, but with lower specificity, include repeated falls and syncope, transient, unexplained loss of consciousness, severe autonomic dysfunction, hallucinations in other modalities, systematized delusions, depression, relative preservation of medial temporal lobe structures on structural neuroimaging, reduced occipital activity on functional neuroimaging, prominent slow wave activity on electroencephalogram, and low uptake myocardial scintigraphy. Management of DLB includes pharmacological and nonpharmacological interventions for its cognitive, neuropsychiatric, motor, and sleep disturbances.
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PMID:Dementia with Lewy bodies. 1722 40

In the field of neurology, Parkinson's disease (PD) is commonly perceived to be a disorder affecting only the (extrapyramidal) motor system, characteristically manifesting as bradykinesia, rigidity, tremor and postural instability. Although non-motor symptoms such as behavioural abnormalities, dysautonomia, sleep disturbances and sensory dysfunctions are also common and quite disabling manifestations of the disease, they are often not formally assessed and thus are frequently misdiagnosed and/or under diagnosed. For this reason, in this review we have concentrated on the pathophysiological and clinical basis of non-motor involvement such as olfactory dysfunction, depression, dementia, dysautonomia and sleep disorders in PD. The early recognition of these symptoms may well perhaps lead to an earlier diagnosis of PD, but in any case should lead to more prompt and effective treatment of the relatively unrecognized non-motor problems associated with PD.
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PMID:Non-motor dysfunction in Parkinson's disease. 1734 13

Drivers' sleepiness and falling asleep while driving account for a considerable proportion of vehicle accidents (studies show different results from 1% to 30%). Sleepiness is rarely well recognised as a causing factor of traffic accidents. 2.5% up to 20% people suffer from excessive daytime sleepiness (EDS) with sleep deprivation as its most frequent cause. There is a strong association between sleep deprivation and medical problems--especially sleep disturbances. The sleep apnoea syndrome (SAS) has been identified as the most common cause of habitual drowsy driving. Patients with SAS (apart from other health problems) are 6 times more likely to have accidents. After adequate treatment of severe SAS with continuous positive airway pressure the risk of accident lowered 5 x. Other important sleep disturbances include chronic insomnia, narcolepsy, restless legs syndrome and periodic limb movement in sleep. Sleepiness was described in Parkinson's disease, dementia, epilepsy, in chronic cardiacs and in people with complex internal health problems. Regular or single intake of drugs (benzodiazepines, antidepressants, antihistaminics, antipsychotics and others) can itself induce sleep problems. Sleepiness in persons without sleep disorder may occur due to preventable causes such as poor sleep habits which lead to sleep deprivation.
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PMID:Medical factors of falling asleep behind the wheel. 1738 1

Inhibition of acetylcholinesterase improves symptoms of dementia in patients with Parkinson's disease (PD). Dementia in PD has a cumulative incidence of up to 80% and is mainly caused by a distinct cholinergic deficit. Objectives of this investigator initiated multicenter open label trial were to confirm the efficacy of donepezil in the treatment of dementia in PD patients and to investigate the tolerability and safety of donepezil. The Mini Mental State Examination (MMSE)-score significantly increased in patients, who finished the trial. A detailed analysis of the various items of the MMSE revealed, that only task performance of orientation and recall significantly improved. Scores of the short syndrome test and the Clinical Global Impression Scale improved, motor impairment did not increase. Only 14 out of 24 PD patients finished the trial due to predominant onset of vomiting, nausea, dizziness and confusion. This may result from the titration regime of donepezil, that allows only 5 and 10 mg dosages. Participants with premature study termination had a significant longer duration of PD, less motivation and sleep disturbances at night. Treatment with donepezil was only effective in PD patients with dementia, who experience nearly no side effects from the drug.
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PMID:The DONPAD-study--treatment of dementia in patients with Parkinson's disease with donepezil. 1744 12

The hypothalamic hypocretin (orexin) system plays a central role in the regulation of various functions, including sleep/wake regulation and metabolism. There is a growing interest in hypocretin function in Parkinson's disease (PD), given the high prevalence of non-motor symptoms such as sleep disturbances in this disorder. However, studies measuring CSF hypocretin levels have yielded contradictory results. In PD patients and matched controls, we (i) estimated the number of hypocretin neurons in post-mortem hypothalami using immunocytochemistry and an image analysis system (ii) quantified hypocretin levels in post-mortem ventricular CSF and (iii) prefrontal cortex using a radioimmunoassay. Furthermore, presence of Lewy bodies was verified in the hypothalamic hypocretin cell area. Data are presented as median (25th-75th percentile). We showed a significant decrease between PD patients and controls in (i) the number of hypocretin neurons (PD: 20 276 (13 821-31 229); controls: 36 842 (32 546-50 938); P = 0.016); (ii) the hypocretin-1 concentration in post-mortem ventricular CSF (PD: 365.5 pg/ml (328.0-448.3); controls: 483.5 (433.5-512.3); P = 0.012) and (iii) the hypocretin-1 concentrations in prefrontal cortex (PD: 389.6 pg/g (249.2-652.2); controls: 676.6 (467.5-883.9); P = 0.043). Hypocretin neurotransmission is affected in PD. The hypocretin-1 concentration in the prefrontal cortex was almost 40% lower in PD patients, while ventricular CSF levels were almost 25% reduced. The total number of hypocretin neurons was almost half compared to controls.
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PMID:Hypocretin (orexin) loss in Parkinson's disease. 1789 5

Several observations suggest a beneficial effect of melatonin antagonism for Parkinson's disease (PD). Although bright light therapy (BLT) suppresses melatonin release and is an established treatment for depression and sleep disturbances, it has not been evaluated in PD. We examined effects of BLT on motor symptoms, depression, and sleep in PD in a randomized placebo-controlled double-blind study in 36 PD patients, using Parkinson's Disease Rating Scale (UPDRS) I-IV, Beck's Depression Inventory, and Epworth Sleepiness Scale. All patients received BLT for 15 days in the morning, 30 min daily. Illuminance was 7.500 lux in the active treatment group and 950 lux in the placebo group. Although group differences were small, BLT led to significant improvement of tremor, UPDRS I, II, and IV, and depression in the active treatment group but not in the placebo group. It was very well tolerated. Follow up studies in more advanced patient populations employing longer treatment durations are warranted.
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PMID:Bright light therapy in Parkinson's disease: a pilot study. 1751 92

The present multicenter cross-sectional study was performed using semistructured questionnaires to determine the contributing factors of sleep disturbances in Japanese patients with Parkinson's disease (PD). We used the Parkinson's disease sleep scale (PDSS, Japanese version). All data were obtained by means of interviewed questionnaire and physical examination by neurologists. The study was carried out between April 2005 and December 2005 at eight university hospitals and affiliated facilities in the Kanto area of Japan. A total of 188 (85 men and 103 women) PD patients and 144 controls (64 men and 80 women) were included. Stepwise regression analysis identified complications of treatment, depression, age, and disease duration as significant risk factors of sleep disturbances in PD. Significant differences in total PDSS score were observed between Hoehn & Yahr (H&Y) Stages 1 and 4, between H&Y Stages 2 and 4, and between H&Y stages 3 and 4 (Bonferroni test). The results of this survey suggested that complications due to treatment (dyskinesia, wearing off, on-off), depressive state, and disease stage are significant determinants of sleep disorders in Japanese patients with PD. We speculate that the reduction of neurotransmitters involved in the sleep-wakefulness mechanism and degeneration of neurons progress together in parallel with deterioration of motor function.
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PMID:Characteristics of sleep disturbances in Japanese patients with Parkinson's disease. A study using Parkinson's disease sleep scale. 1755 25

There is growing evidence that a variety of symptoms can precede the classical motor features of Parkinson's disease (PD). The period when these symptoms arise can be referred to as the premotor phase of the disease. Well-documented premotor symptoms in PD include constipation, loss of smell, sleep disturbances such as REM sleep behavior disorder (RBD), and mood disturbances like depression. Diagnostic and therapeutic implications linked to improved identification of these premotor features are discussed.
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PMID:The premotor phase of Parkinson's disease. 1768 39


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