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)

In the absence of pathognomonic clinical features, the clinical diagnosis of Alzheimer's disease (AD) remains one of exclusion of other dementias. We investigated the clinical diagnoses among 394 neuropathologically confirmed AD cases in a dementia brain bank. Most patients were correctly diagnosed as AD (348 or 88%). Among the misdiagnosed patients, AD was mistaken for a primary depressive disorder in 14, multi-infarct dementia in 13, Parkinson's disease in nine, and alcoholic dementia in four. The number of misdiagnosed AD patients did not differ between physician specialties but was greater among AD patients with agitation, depression, paranoia, or delusions. This retrospective study suggests that the diagnostic sensitivity for AD is high among a cross-section of practicing physicians and that an important factor in mistaking AD for another illness is unfamiliarity with the potential psychiatric symptoms of AD.
 ...
PMID:Neuropathologically confirmed Alzheimer's disease: clinical diagnoses in 394 cases. 205 48

We present three patients who, after long-term therapy with amantadine (4 to 18 years), experienced an acute delirium with confusion, disorientation, agitation, and paranoia on withdrawal. These patients had Parkinson's disease for 5 to 29 years; mean age was 73 years. All had a history of varying degrees of dementia and transient hallucinations in the past. Adjustment of other medications was ineffective in improving their condition and no other cause was found. Only with reinstitution of amantadine did the patients return to baseline status (usually within days).
 ...
PMID:Acute delirium after withdrawal of amantadine in Parkinson's disease. 1033 17

We investigated the availability of dopamine reuptake sites in the striata of two patients with productive symptoms and neuroleptic therapy as well as progressive parkinsonism using the new dopamine transporter ligand [123I]N-(3-iodopropen-2-yl)-2beta-carbo-methoxy-3beta- (4-chlorophenyl)tropane (IPT) and single photon emission computed tomography (SPECT). Normal specific binding in the caudate nucleus was 8.6 +/- 1.2 and in the putamen 6.5 +/- 1.3 (mean +/- S.D.; n = 8; mean age, 56.7 years; range 41-67 years). Patient 1 (age 43) was admitted to our clinic at age 38 because of left-sided parkinsonism. At age 40, she developed paranoid psychosis without change after cessation of L-DOPA and lisuride treatment for 3 months. She was diagnosed as a schizophrenic, paranoid subtype (DSM-III-R). IPT-SPECT showed a loss of dopaminergic nerve terminals (right caudate/putamen, 5.16/2.0; left caudate/putamen, 5.92/2.66). Patient 2 (age, 61 years) had a history of paranoid psychosis for approx. 30 years. He experienced progressive right-sided parkinsonism since age 57 when treated with clozapine. IPT-SPECT showed a marked reduction of striatal dopamine transporter binding (right caudate/putamen, 5.06/1.65; left caudate/putamen, 3.8/1.12). Our findings indicate that patients may suffer contemporaneously from Parkinson's disease and schizophrenia. In these patients, the proof of a nigrostriatal dopaminergic deficit justifies treatment with neuroleptics and dopaminergic drugs. Imaging of dopamine transporters with SPECT and IPT or a related compound represents an attractive alternative to the more complex measurements of fluorodopa uptake with positron emission tomography (PET).
 ...
PMID:Reduced striatal dopaminergic innervation shown by IPT and SPECT in patients under neuroleptic treatment: need for levodopa therapy? 975 2

Eleven patients with Parkinson's disease (PD) and acute psychosis received flexible doses of quetiapine between 25 and 300 mg/day based on clinical response and tolerance. Ten patients were receiving dopaminergic agents at baseline. Serial efficacy ratings (Brief Psychiatric Rating Scale, Clinical Global Impressions Scale), neuromuscular symptom assessments (Abnormal Involuntary Movement Scale, Simpson-Angus Scale, Unified Parkinson's Disease Rating Scale [UPDRS]), and adverse events monitoring were performed for up to 52 weeks. The patients had moderate hallucinations and/or delusions at baseline before the initiation of quetiapine. Nine of the 11 patients completed at least 12 weeks of treatment. Quetiapine was well tolerated in all but one patient, who became dizzy within the first week and withdrew from the study. Ten patients presented with moderate visual hallucinations. Quetiapine was markedly effective in controlling visual hallucinations in six of these patients. Symptoms of paranoia or delusions were less responsive to quetiapine. Four patients withdrew because of adverse events or comorbid medical problems, two withdrew because of a lack of efficacy, and five completed 52 weeks of treatment. The introduction of quetiapine did not exacerbate parkinsonian symptoms. Motor dysfunction, as measured by the UPDRS, revealed a slow, gradual worsening consistent with the progression of PD. Atypical antipsychotic medications such as quetiapine have a reduced likelihood of causing adverse drug-induced parkinsonism and therefore a possible role in treating psychotic symptoms in patients with PD.
 ...
PMID:Efficacy of quetiapine in Parkinson's patients with psychosis. 1065 9

Psychotic symptoms are a common complication in Parkinson's disease with dementia. The authors conducted an open-label 6-week trial of olanzapine preceded by a placebo lead-in in five subjects with Parkinson's disease, mild to moderately severe dementia, and psychosis. Four of the subjects terminated the trial early because of worsening motor function, sedation, or paranoia. There was no improvement in psychotic symptoms, and functional abilities declined significantly. Olanzapine appears to be poorly tolerated in patients with Parkinson's disease, psychotic symptoms, and dementia.
 ...
PMID:Olanzapine for the treatment of psychosis in patients with Parkinson's disease and dementia. 1181 82

The dopamine transporter gene (DAT) has been implicated in a variety of disorders, including bipolar disorder, attention-deficit hyperactivity disorder, cocaine-induced paranoia, Tourette's syndrome, and Parkinson's disease. As no clear functional polymorphism has been identified to date, studies rely on linkage disequilibrium (LD) to assess the possible genetic contribution of DAT to the various disorders. A better understanding of the complex structure of LD across the gene is thus critical for an accurate interpretation of the results of such studies, and may facilitate the mapping of the actual functional variants. In the process of characterizing the extent of variation within the DAT gene, we have identified a number of single nucleotide polymorphisms (SNPs) suitable for LD studies, 14 of which have been analyzed, along with a 3' repeat polymorphism, in a sample of 120 parent-proband triads. Calculations of pairwise LD between the SNPs in the parental haplotypes revealed a high degree of LD (P < 0.00001) in the 5' (distal promoter through intron 6) and 3' (exon 9 through exon 15) regions of DAT. This segmental LD pattern is maintained over approximately 27 kb and 20 kb in these two regions, respectively, with very little significant LD between them, possibly due to the presence of a recombination hotspot located near the middle of the gene. These analyses of the DAT gene thus reveal a complex structure resulting from both recombination and mutation, knowledge of which may be invaluable to the design of future studies.
 ...
PMID:Segmental linkage disequilibrium within the dopamine transporter gene. 1184 Mar 9

Alpha-synuclein is a presynaptic protein that has been implicated as a possible causative agent in the pathogenesis of Parkinson's disease. The native protein is a major component of nigral Lewy bodies in Parkinson's disease, and full-length alpha-synuclein accumulates in Lewy neurites. Here we present evidence that alpha-synuclein levels are elevated in midbrain dopamine (DA) neurons of chronic cocaine abusers. Western blot and immunoautoradiographic studies were conducted on postmortem neuropathological specimens from cocaine users and age-matched drug-free control subjects. The results demonstrated that alpha-synuclein levels in the DA cell groups of the substantia nigra/ventral tegmental complex were elevated threefold in chronic cocaine users compared with normal age-matched subjects. The increased protein levels in chronic cocaine users were accompanied by changes in the expression of alpha-synuclein mRNA in the substantia nigra and ventral tegmental area. Although alpha-synuclein expression is prominent in the hippocampus, there was no increase in protein expression in this brain region. The levels of beta-synuclein, a possible negative regulator of alpha-synuclein, also were not affected by cocaine exposure. Alpha-synuclein protein levels were increased in the ventral tegmental area, but not the substantia nigra, in victims of excited cocaine delirium who experienced paranoia, marked agitation, and hyperthermia before death. The overexpression of alpha-synuclein may occur as a protective response to changes in DA turnover and increased oxidative stress resulting from cocaine abuse. However, the accumulation of alpha-synuclein protein with long-term cocaine abuse may put addicts at increased risk for developing the motor abnormalities of Parkinson's disease.
 ...
PMID:Cocaine abusers have an overexpression of alpha-synuclein in dopamine neurons. 1268 41

In the late-stage idiopathic Parkinson's disease (IDP), comorbid conditions such as depression and drug-induced psychosis may be observed. A patient with Parkinson disease, major depression, and paranoid psychosis who developed neuroleptic malignant syndrome (NMS) as the result of the sudden termination of high-dose (1200 mg/d) levodopa treatment is presented in this report. Because the patient did not respond to other treatment modalities, electroconvulsive therapy (ECT) was applied, and a rapid improvement was observed both in the patient's NMS and also in Parkinson's and psychiatric symptoms, with no additional side effects other than transient post-ictal confusions. The application of ECT allowed the patient to remain stable for a 5-year period with a quite low dose of levodopa (300 mg/d). Later, the patient had two episodes of depressive and psychotic symptoms, which were again successfully treated with the ECT. We suggest that ECT might be an effective and life-saving therapy in patients with severe, drug-resistant NMS.
 ...
PMID:Electroconvulsive therapy in drug-induced psychiatric states and neuroleptic malignant syndrome. 1590 57

The neuropsychiatry of Parkinson's disease (PD) and its correlates are reviewed. Dementia occurs in up to 30% and can be treated with cholinesterase inhibitors. Cognitive impairments involve executive, visuospatial, attentional, and memory dysfunctions. Apathy may respond to dopamine agonists or cholines-terase inhibitors. Cognitive impairment, psychosis, and depression predict quality of life. Visual hallucinations and paranoia are common, and respond to low dose clozapine. Depression is common and predicts caregiver burden and depression. The best data suggest the efficacy of nortriptyline and the safety of SSRIs. Anxiety disorders occur in 40% of patients, especially off-period panic attacks and specific phobias. Bromazepam has proven useful for anxiety in PD, but buspirone has only diminished drug-induced dyskinesias to date. Sleep disorders occur in up to 94% of patients. Insomnia is common and is treated by dopaminergic agent dose reduction, nocturnal dosing, treatment of depression, or use of short half-lived hypnotics, depending on etiology. Parasomnias include REM behavior disorder and vivid dreams and nightmares. Excessive daytime somnolence occurs in at least 15% of patients. Sleep attacks are common and patients should be warned about driving when taking dopamine agonists. Sexual disorders occur in most patients. Paraphilias are associated with dopamine agonists, and clozapine may be useful in their treatment. Surgical therapies are associated with a wide variety of neuropsychiatric features, and vigilance for suicide attempts with subthalamic nucleus stimulation seems warranted. Neuropsychiatric disorders are important determinants of quality of life and caregiver burden in PD. More clinical research is needed to establish effective treatments.
 ...
PMID:The neuropsychiatry of Parkinson's disease. 1617 59

Progress in pharmacology has markedly improved the treatment of early Parkinson's disease. The management of advanced Parkinson's symptoms, however, remains a challenge. These symptoms are divided into motor and non-motor symptoms. Non-motor symptoms may appear early or late in the disease and sometimes even before the onset of the first motor symptoms confirming the diagnosis. The spectrum of non-motor symptoms encompasses autonomic dysfunctions, sleep disorders, mood disorders, impulse control disorders, cognitive dysfunction, dementia, paranoia and hallucinations. They are often less appreciated than motor symptoms but are important sources of disability for many PD patients. This review describes these non-motor symptoms and their managements.
 ...
PMID:Management of non-motor symptoms in advanced Parkinson disease. 1780 18


1 2 Next >>