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)

The neuropathology of human sleep remains an ill-defined issue. The data concerning the main structures of human brain areas involved, or supposed to be implicated, in sleep organisation are reviewed. Five levels of organisation can be schematically recognized: (i) the ascending arousal system, (ii) the non REM and REM systems (iii) regulated by hypothalamic areas, (iv) and the biological clock, (v) modulated by a number of "allostatic" influences. These are briefly described, with emphasis on the location of structures involved in humans, and on the recently revised concepts. Current knowledge on the topography of lesions associated with the main sleep disorders in degenerative diseases is recalled, including REM sleep behavior disorders, restless legs syndrome and periodic leg movements, sleep apneas, insomnia, excessive daily sleepiness, secondary narcolepsy and disturbed sleep-wake rhythms. The lesions of sleep related structures observed in early and late stages of four degenerative diseases are then reviewed. Two synucleinopathies (Lewy lesions associated disorders, including Parkinson's disease and Dementia with Lewy bodies, and Multiple System Atrophy) and two tauopathies (Progressive Supranuclear Palsy and Alzheimer's disease) are dealt with. The distribution of lesions usually found in affected patients fit with that expected from the prevalence of different sleep disorders in these diseases. This confirms the current opinion that these disorders depend on the distribution of lesions rather than on their biochemical nature. Further studies might throw insight on the mechanism of normal and pathological sleep in humans, counterpart of the increasing knowledge provided by animal models. Specially designed prospective clinicopathological studies including peculiar attention to sleep are urgently needed.
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PMID:[The neuropathology of sleep in human neurodegenerative diseases]. 1876 Apr 29

For more than 50 years, Parkinson's disease (PD) has been conceptualized as a product of nigro-striatal dopamine (NSD) system degeneration. In spite of a growing body of evidence depicting the mammalian brain as an interrelated complexity of circuitous systems, dopamine (DA) deficiency of the NSD is still regarded as the main problem, with DA replacement being the purpose of therapeutic intervention. For at least 191 years circadian involvement in various aspects of PD, including depression and insomnia, has been recognized as an integral part of the symptom matrix of PD and yet attempts to elucidate the involvement of this system is uncharted territory. The present review attempts a major reorganization of mammalian brain into a coordinated complex involving the NSD and the retinal hypothalamic tract (RHT) as the primary systems involved in the retino-diencephalic/mesencephalic-pineal (RDMP) axis. Secondary systems including the lateral hypothalamus (LH), the area postraema (AP) and the subthalamic nucleus (STN) also form an integral part of this system as they have been shown to be either intimately related to the primary systems of the RDMP axis or have been shown to be significantly involved in the expression and treatment of PD. A large volume of evidence suggests that the RDMP axis is activated during the course of PD and during therapeutic intervention. Four types of neurotoxicity associated with melatonin are identified and the susceptibility of various parts of the RDMP axis to undergo neuropathological change, the tendency for melatonin to induce PD-like behavioural toxicity, and the relationship of this to PD symptomotology are described. This includes adverse effects of melatonin on motor function, hypotension, the adjuvant use of benzodiazepines, depression, insomnia, body weight regulation and various biochemical effects of melatonin administration: all problems currently facing the proposal to introduce melatonin as an adjuvant. It is suggested further that traditional DA replacement may well work by exerting its effect upon the circadian system, rather than simply replacing deficient DA. Activation of the circadian function by antagonizing melatonin with bright light not only has therapeutic value in treating the primary symptoms of PD but it shares a common mechanism with L-dopa in reducing the occurrence of seborrheic dermatitis. Concepts at the centre of understanding pineal function in PD, including pineal calcification, melatonin deficiency, symptomatic versus protective features of melatonin and antioxidative effects, are explained in a counterintuitive context. Intriguing propositions including the role of the retina in the aetiology of PD and that the nigra functions as a retina in this disorder are presented with the intention to provide a new understanding of the underlying compromised function in PD and to provide new treatment strategies. For the first time, abundant evidence is presented describing PD as an endocrine disorder of melatonin hyperplasia. The role of circadian interventive therapies and internal desynchrony in the aetiology and progression of PD provides a new direction for understanding the underlying physiology of a disease which is currently in a state of impasse and provides new hope for those who suffer from its debilitating effects.
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PMID:Parkinson's disease as a neuroendocrine disorder of circadian function: dopamine-melatonin imbalance and the visual system in the genesis and progression of the degenerative process. 1914 86

Sleep disturbances are widespread among older adults. Degenerative neurologic disorders that cause dementia, such as Alzheimer's disease and Parkinson's disease, exacerbate age-related changes in sleep, as do many common comorbid medical and psychiatric conditions. Medications used to treat chronic illness and insomnia have many side effects that can further disrupt sleep and place patients at risk for injury. This article reviews the neurophysiology of sleep in normal aging and sleep changes associated with common dementia subtypes and comorbid conditions. Current pharmacologic and nonpharmacologic evidence-based treatment options are discussed, including the use of light therapy, increased physical and social activity, and multicomponent cognitive-behavioral interventions for improving sleep in institutionalized and community-dwelling adults with dementia.
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PMID:Current treatments for sleep disturbances in individuals with dementia. 1918 4

Levodopa has been the gold standard therapy for the motor symptoms of Parkinson's disease for more than three decades. Although it remains the most effective treatment, its long-term use is associated with motor fluctuations and dyskinesias that can be disabling for patients and difficult for physicians to manage medically. In the last 10 years, the catechol-O-methyltransferase (COMT) inhibitor tolcapone has been studied for its efficacy as an adjunctive treatment to levodopa plus a dopa decarboxylase inhibitor. Adjunctive therapy with tolcapone can significantly reduce the dose of levodopa required. Moreover, treatment with tolcapone significantly reduces wearing off and on-off periods in fluctuating patients and improves 'on' time in patients with stable disease. Tolcapone has assumed a new place in the arsenal of medications for Parkinson's disease. This paper reviews the pharmacology, safety and efficacy of tolcapone in patients with advanced Parkinson's disease. After some initial concerns about its safety, tolcapone has been shown to be safe if used and monitored according to guidelines regarding liver function. Tolcapone produces expected dopaminergic side effects, including headache, nausea, insomnia, as well as diarrhea; however, these side effects are generally mild and as a rule do not result in discontinuation of therapy.
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PMID:Tolcapone: review of its pharmacology and use as adjunctive therapy in patients with Parkinson's disease. 1950 73

We performed a multicenter survey using a semistructured interview in 1,072 consecutive patients with Parkinson's disease (PD) enrolled during 12 months in 55 Italian centers to assess the prevalence of nonmotor symptoms (NMSs), their association with cognitive impairment, and the impact on patients' quality of life (QoL). We found that 98.6% of patients with PD reported the presence of NMSs. The most common were as follows: fatigue (58%), anxiety (56%), leg pain (38%), insomnia (37%), urgency and nocturia (35%), drooling of saliva and difficulties in maintaining concentration (31%). The mean number of NMS per patient was 7.8 (range, 0-32). NMS in the psychiatric domain were the most frequent (67%). Frequency of NMS increased along with the disease duration and severity. Patients with cognitive impairment reported more frequently apathy, attention/memory deficit, and psychiatric symptoms. Apathy was the symptom associated with worse PDQ-39 score but also presence of fatigue, attention/memory, and psychiatric symptoms had a negative impact on QoL. These findings further support a key role for NMS in the clinical frame of PD and the need to address them specifically in clinical trials using dedicated scales.
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PMID:The PRIAMO study: A multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson's disease. 1951 14

Restless legs syndrome (RLS) is a sensorimotor disorder, characterized by an irresistible urge to move the legs and usually accompanied or caused by uncomfortable and unpleasant sensations. It begins or worsens during periods of rest or inactivity, is partially or totally relieved by movement and is exacerbated or occurs mainly in the evening or night. People suffering from RLS are estimated to represent 2-3% of the general Japanese population, which is relatively lower than the estimated prevalence in western countries. Supportive diagnostic critevia include family history, the presence of periodic-leg movements (PLM) when awake or asleep, and a positive response to dopaminergic treatment. RLS phenotypes include an early onset form that is usually idiopathic with frequent familial history and a late onset form that is usually secondary to other somatic conditions that are causative factors in RLS occurrence. In all patients presenting with complaints of insomnia or discomfort in the lower limbs, diagnosis of RLS should be considered. RLS should be differentiated from akathisia, which is an urge to move the whole body in the absence of uncomfortable sensations. Polysomnographic studies and the suggested immobilization test (SIT) can detect PLM in patients that are asleep or awake. RLS may cause severe sleep disturbances, poor quality of life, depressive and anxious symptoms, and may be a risk factor for cardiovascular disease. Secondary RLS may occur due to iron deficiency, end-stage renal disease, pregnancy, peripheral neuropathy and drug use including antipsychotics and antidepressants. Small fiber neuropathy can trigger RLS or mimic its symptoms. RLS is associated with many neurological disorders, including Parkinson disease and multiple system atrophy; althoughit does not predispose to these diseases. A symptom rating scale for RLS authorized by the International RLS Study Group (IRLS) would facilitate accurate diagnosis of this condition.
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PMID:[Diagnosis and symptom rating scale of restless legs syndrome]. 1951 13

Parkin gene mutations cause a juvenile parkinsonism. Patients with these mutations may commonly exhibit REM sleep behaviour disorders, but other sleep problems (insomnia, sleepiness, restless legs syndrome) have not been studied. The aim of this study was to evaluate the sleep-wake phenotype in patients with two parkin mutations, compared with patients with idiopathic Parkinson's disease (iPD). Sleep interview and overnight video-polysomnography, followed by multiple sleep latency tests, were assessed in 11 consecutive patients with two parkin mutations (aged 35-60 years, from seven families) and 11 sex-matched patients with iPD (aged 51-65 years). Sleep complaints in the parkin group included insomnia (73% patients versus 45% in the iPD group), restless legs syndrome (45%, versus none in the iPD group, P = 0.04), and daytime sleepiness (45%, versus 54% in the iPD group). Of the parkin patients, 45% had REM sleep without atonia, but only 9% had a definite REM sleep behavior disorder. All sleep measures were similar in the parkin and iPD groups. Two parkin siblings had a central hypersomnia, characterized by mean daytime sleep latencies of 3 min, no sleep onset REM periods, and normal nighttime sleep. Although the patients with two parkin mutations were young, their sleep phenotype paralleled the clinical and polygraphic sleep recording abnormalities reported in iPD, except that restless legs syndrome was more prevalent and secondary narcolepsy was absent.
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PMID:Restless legs syndrome, rapid eye movement sleep behavior disorder, and hypersomnia in patients with two parkin mutations. 1967 85

Sleep disorders occur commonly in Parkinson's disease (PD), and reduce quality of life. Sleep-related problems in PD include insomnia, restless legs syndrome, rapid eye movement sleep behavior disorder, sleep apnea, parasomnias, excessive daytime sleepiness, and sleep attacks. This article reviews sleep disorders and their treatment in PD.
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PMID:Sleep disorders in Parkinson's disease. 1989 67

Polysomnographic studies of Parkinson's disease (PD) patients with visual hallucinations (VH) usually reveal short, fragmented rapid eye movement (REM) sleep, with lower sleep efficiency and reduced total REM sleep. Quetiapine has been demonstrated in open-label trials to be effective for the treatment of insomnia and VH in PD. To confirm quetiapine's efficacy in improving VH, and to determine whether the mechanism was due to its effect on REM sleep architecture, we performed a pilot, double-blind, placebo-controlled study. Sixteen PD patients experiencing VH were recruited. Eight patients were randomized to quetiapine and eight patients to placebo. Patients underwent pre- and post-treatment polysomnography. The Clinical Global Impression Scale (CGIS), Brief Psychiatric Rating Scale (BPRS), and Unified Parkinson Disease Rating Scale (UPDRS) motor subscale were obtained. There were no differences in baseline characteristics between the treatment arms except that the placebo group had more sleep in stage REM (74.7 min vs. 40.1 min; p < .001). Data were imputed for all patients who prematurely discontinued (four quetiapine and one placebo) in an intention-to-treat analysis. The average quetiapine dose was 58.3 mg/day. While there was no significant difference in the change in REM duration pre- vs. post-treatment in either arm, patients randomized to quetiapine improved on the CGIS (p = .03) and the hallucination item of the BPRS (p = .02). No difference was noted in the UPDRS motor scores. Despite the small sample, this is the first double-blind trial to show quetiapine's efficacy over placebo in controlling VH in the PD population. However, normalization of sleep architecture was not supported as the mechanism.
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PMID:Quetiapine improves visual hallucinations in Parkinson disease but not through normalization of sleep architecture: results from a double-blind clinical-polysomnography study. 1991 48

Parkinson's disease (PD) is a progressive disorder with a presymptomatic interval; that is, there is a period during which the pathologic process has begun, but motor signs required for the clinical diagnosis are absent. There is considerable interest in discovering markers to diagnose this preclinical stage. Current predictive marker development stems mainly from two principles; first, that pathologic processes occur in lower brainstem regions before substantia nigra involvement and second, that redundancy and compensatory responses cause symptoms to emerge only after advanced degeneration. Decreased olfaction has recently been demonstrated to predict PD in prospective pathologic studies, although the lead time may be relatively short and the positive predictive value and specificity are low. Screening patients for depression and personality changes, autonomic symptoms, subtle motor dysfunction on quantitative testing, sleepiness and insomnia are other potential simple markers. More invasive measures such as detailed autonomic testing, cardiac MIBG-scintigraphy, transcranial ultrasound, and dopaminergic functional imaging may be especially useful in those at high risk or for further defining risk in those identified through primary screening. Despite intriguing leads, direct testing of preclinical markers has been limited, mainly because there is no reliable way to identify preclinical disease. Idiopathic RBD is characterized by loss of normal atonia with REM sleep. Approximately 50% of affected individuals will develop PD or dementia within 10 years. This provides an unprecedented opportunity to test potential predictive markers before clinical disease onset. The results of marker testing in idiopathic RBD with its implications for disease prediction will be detailed.
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PMID:Predicting Parkinson's disease - why, when, and how? 2008 67


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