40 research outputs found
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Reappraisal of Temporary Levodopa Withdrawal ("Drug Holiday") in Parkinson's Disease
Transient withdrawal of therapy has been advocated as a method of dealing with the complications of long-term use of levodopa in the treatment of Parkinson's disease. We retrospectively examined the effect of a 10-day period of levodopa withdrawal, or "drug holiday," in 28 patients. We then compared the subsequent clinical course of these patients over one year with that of 30 other randomly selected, similar patients with Parkinson's disease. In both groups the disease progressed; there was no difference in disease severity, capacity for daily living activities, or total amounts of dopamine agonists eventually used. For some patients, it was possible to reduce dopamine agonists used immediately after the drug holiday without causing deterioration, but a pulmonary embolus and other complications occurred. Subsequent complications related to long-term dopamine-agonist therapy during the follow-up period were similar in the two groups. This investigation indicates that a drug holiday carries some risk and does not improve the efficacy of levodopa therapy or prevent the problems that occur with long-term administration
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Relationships between Extrapyramidal Signs and Cognitive Function in a Community-Dwelling Cohort of Patients with Parkinson's Disease and Normal Elderly Individuals
The relationship between extrapyramidal sign(DPS) severity and cognitive funcition was investigated in 184 patients with indiopathic Parkinson's disease (PD) and 301 normal elderly individuasls from a community-dwelling cohort in northern Manhattan, New York City. Fifiy-six of the patients with PD met criteria for dementia of the Diagnostic and Statistical Manual of Mental Disorders third edition, revised, and of the National Institute of Neurological and Communicative Disorders and Stroke-Alzbeimer's Disease and Related Disorders Association. EPS were rated according to the Unified Parkinson's Disease Rating Scale. Cognitive function was assessed by neuropsychological rests of memory, orientation, abstract reasoning, language, construcion, and psychomotor speed. Significant associations were found between EPS and neuropsychological performance in PD partients without dementia. Yet EPS severity was unable to account for the pronounced cognitive impairment in PD dementia. Individuals in the normal group with subtle EPS, but withtout overt idiopathic PD, showed widespread cognitive changes, including imparment in most of the tests that differentiated PD patients from normal subjects. Prospective follow-up of these individuals will determine whether this represents a preclinical stage of PD or constitutes an early manifestation of dementia
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Relationships between Extrapyramidal Signs and Cognitive Function in a Community-Dwelling Cohort of Patients with Parkinson's Disease and Normal Elderly Individuals
The relationship between extrapyramidal sign(DPS) severity and cognitive funcition was investigated in 184 patients with indiopathic Parkinson's disease (PD) and 301 normal elderly individuasls from a community-dwelling cohort in northern Manhattan, New York City. Fifiy-six of the patients with PD met criteria for dementia of the Diagnostic and Statistical Manual of Mental Disorders third edition, revised, and of the National Institute of Neurological and Communicative Disorders and Stroke-Alzbeimer's Disease and Related Disorders Association. EPS were rated according to the Unified Parkinson's Disease Rating Scale. Cognitive function was assessed by neuropsychological rests of memory, orientation, abstract reasoning, language, construcion, and psychomotor speed. Significant associations were found between EPS and neuropsychological performance in PD partients without dementia. Yet EPS severity was unable to account for the pronounced cognitive impairment in PD dementia. Individuals in the normal group with subtle EPS, but withtout overt idiopathic PD, showed widespread cognitive changes, including imparment in most of the tests that differentiated PD patients from normal subjects. Prospective follow-up of these individuals will determine whether this represents a preclinical stage of PD or constitutes an early manifestation of dementia
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The Frequency and Associated Risk Factors for Dementia in Patients with Parkinson's Disease
Objectives: To estimate the frequency and determine the risk factors for incident dementia in community-dwelling patients with Parkinson's disease (PD) and in control subjects. Design: Prospective cohort study. During a 3.5-year period, 140 patients with idiopathic PD without evidence of dementia and 572 nondemented control subjects were identified in the community of Washington Heights—Inwood in New York, NY. All subjects underwent neurological and neuropsychological evaluations and follow-up examinations. Results: Twenty-seven patients with PD (19.2%) became demented throughout 2 years, as compared with 87 (15.2%) of the control subjects. The relative risk (RR) for the development of dementia with PD was 1.7 (95% confidence interval [CI], 1.1 to 2.7) after adjusting for age, education, and gender. Predictive features of incident dementia were an extrapyramidal score greater than 25 (RR, 3.56; 95% CI, 1.4 to 8.9) and a Hamilton Depression Rating Scale score greater than 10 (RR, 3.55; 95% CI, 1.6 to 7.9). Conclusion: Patients with PD, especially those with severe extrapyramidal signs, have almost twice the risk for the development of dementia than do community-dwelling control subjects
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Smoking and Parkinson's Disease
Smoking was examined in relation to Parkinson's disease (PD) in a population-based study in northern Manhattan (New York City) because of its putative “protective effect.” Using a case-control design, information on smoking and associated behaviors was obtained in structured interviews after standard diagnostic evaluations in both cases and controls. The overall prevalence of smoking in the population was 43.7%, decreasing to 37% after age 85. Smoking was most frequent in men, Blacks, and in both cases and controls using alcohol once per week or more. Cases had quit smoking more often than controls (87 vs. 64%), and had smoked for significantly fewer years (31 vs. 41 yrs; p < 0.05 for both). The age-at-onset for smokers with PD was similar to age-at-onset for nonsmokers with PD. The odds ratio (OR) for a history of smoking associated with PD was 1.1 (95% CI 0.7–1.8). No protective gradient was associated with heavier smoking patterns. However, the odds that patients with PD were still smoking at the time of the interview were significantly less than those for controls (OR = 0.2; 95% CI 0.1–0.5). These results do not support the hypothesis that smoking protects against PD; rather they strongly imply the converse, that PD reduces smoking
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The Relationship of Serotonin to Depression in Parkinson's Disease
We have previously reported a correlation between depression in patients with idiopathic Parkinson's disease and decreased concentrations of the cerebrospinal fluid content of the serotonin metabolite, 5-HIAA. To further examine this relationship, we repeated the study in a new cohort of patients while they remained on dopaminergic medications, conducted follow-up interviews and examinations in our original cohort, and conducted an open trial of the serotonin precursor, 5-hydroxytryptophan in a group of new patients with depression. We were again able to demonstrate a significant reduction in cerebrospinal 5-HIAA in depressed patients in comparison to controls and patients without depression. Demented patients with Parkinson's disease, particularly those with concurrent depression, had the lowest values of 5-HIAA. No new cases of depression occurred in our orignial cohort after 21/2 years of follow-up, and depression remitted following conventional or experimental treatment in four patients. Depression improved in six of the seven new patients following oral 5-hydroxytryptophan. Three of these patients allowed a repeat lumbar puncture, and the concentration of 5-HIAA increased following 5-hydroxytryptophan. These three studies support our hypothesis that depression in idiopathic Parkinson's disease is associated with a reduction in brain serotonin. However, it also suggests that other factors, biological or environmental, may be causal factors
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Neuropsychological Characteristics of Preclinical Dementia in Parkinson's Disease
The goal of this study was to characterize the changes in cognition associated with the earliest, or preclinical, stages of dementia in Parkinson's disease (PD). We administered a comprehensive neuropsychological test battery to a group of initially nondemented PD patients participating in a longitudinal community-based epidemiologic study. We used Cox proportional hazards models to assess the relative risk of incident dementia associated with baseline scores on the neuropsychological tests. Baseline performance on two verbal fluency tasks (letter fluency and category fluency) was significantly and independently associated with incident dementia. Tests of memory, orientation, abstract reasoning, naming, and constructional skill were less sensitive predictors of subsequent dementia. The neuropsychological pattern characterizing the preclinical stages of dementia in PD differed from that described previously in preclinical Alzheimer's disease. Results suggest that poor performance on tests of verbal fluency may represent a distinct characteristic of the preclinical phase of dementia in PD
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An Estimate of the Prevalence of Dementia in Idiopathic Parkinson's Disease
A review of the records for evidence of dementia using criteria adapted from the third edition of the Diagnostic and Statistical Manual of Mental Disorders in every patient (hospitalized and outpatient) with parkinsonism at a major medical center during an 18-month period revealed an overall prevalence of 10.9% in 339 patients with idiopathic Parkinson's disease. Demented patients were older, had a later age at onset of motor manifestations, and a more rapid progression of physical disability than nondemented patients. Duration of illness and levodopa use and the presence of tremor or depression were similar in demented and nondemented patients. Demented patients more often responded poorly or developed adverse effects to levodopa than nondemented patients. When Parkinson's disease began after age 70 years, dementia was noted over three times more frequently than when the disease began at an earlier age. The age-specific prevalence rate of dementia for patients older than 70 years was more than twice that for younger patients. Moreover, the number of records with evidence for dementia with idiopathic Parkinson's disease was 3.75 times greater than expected in comparison with data from a study of the prevalence of dementia in the elderly
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Coexisting Dementia and Depression in Parkinson's Disease
Dementia and depression in patients with Parkinson's disease have been reported separately, but their prevalence is controversial. This study examines the coexistence of these two problems and suggests a common underlying biochemical system. We examined these two entities by retrospective chart review and cerebrospinal fluid biochemistry. We found a prevalence of 10.9% for dementia, 51% for depression, and 5.4% for coincident depression and dementia. In a prospective study of patients with Parkinson's disease we found a continuum of cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations. Patients who were either depressed or demented had lower concentrations of this metabolite than other patients with Parkinson's disease, but patients who were depressed and demented had the lowest levels. These results suggest that the coexistence of dementia and depression represents a unique clinical entity in Parkinson's disease. The serotonergic system may be involved in depression and dementia because evidence of a cumulative effect on this biochemical system is present
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A Population-Based Investigation of Parkinson's Disease with and without Dementia: Relationship to Age and Gender
Because the prevalence of idiopathic Parkinson's disease (PD) with or without dementia remains controversial, we initiated a population-based investigation in the Washington Heights—Inwood section of New York, NY, so that nearly complete case ascertainment could be achieved. A "registry" was developed for the study, and we advertised in periodicals and on radio and television. Subjects, or their records, were examined by experienced neurologists, and most underwent a battery of neuropsychological tests specifically designed for assessment in this community. All data were reviewed by a team of clinicians to achieve a consensus diagnosis. The crude prevalence of idiopathic PD, with and without dementia, was 99.4 per 100 000, increasing from 2.3 per 100 000 for those younger than 50 years to 1144.9 per 100 000 for those aged 80 years and older. The crude prevalence for PD with dementia alone was 41.1 per 100 000 and also increased with age from zero for those younger than 50 years to 787.1 per 100 000 for those aged 80 years and older. Prevalence ratios were comparable with those of other published population-based studies in similar settings. After standardization, men had PD with and without dementia more frequently than did women. The major difference between patients with and without dementia was a later estimated age at onset of motor manifestations. We conclude that PD is a frequent disorder in the elderly population that affects men and whites more frequently than women and nonwhites. Moreover, dementia in patients with PD is more frequent than previously recognized and is strongly related to the age at onset of motor manifestations