Biomedical subjects

J P Larsen

Publications and source records attributed to J P Larsen.

At least 19 recordsLinked to original sources

PubMed2006

Differences in neuropathologic characteristics across the Lewy body dementia spectrum.

BACKGROUND: The objective of this comparative neuropathologic study was to determine the extent to which dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD) are distinct entities or part of a continuum with respect to the duration of parkinsonism. METHODS: We evaluated the relationship between cortical alpha-synuclein pathology, plaques (Consortium to Establish a Registry for Alzheimer's Disease [CERAD]), tangles (Braak staging), and cholinergic deficits (choline acetyltransferase in temporal cortex) in 57 prospectively assessed patients (29 DLB, 28 PDD), confirmed at autopsy. The PDD group was divided according to the median duration of parkinsonism prior to dementia. RESULTS: There was an association between longer duration of parkinsonism prior to dementia and less severe cortical alpha-synuclein pathology (chi(2) 10.4, df 2, p = 0.006) and lower CERAD plaque scores (chi(2) 26.6, df 9, p = 0.002), but not Braak staging. These findings were confirmed in a further correlation analysis, which also identified an unexpected correlation between more pronounced cortical cholinergic deficits and longer duration of parkinsonism prior to dementia (R = -0.37, p = 0.04). CONCLUSION: While there is a clear relationship between the duration of Parkinson disease prior to the onset of dementia and key neuropathologic and neurochemical characteristics, there is a gradation of these differences across the dementia with Lewy bodies/Parkinson disease dementia spectrum and the findings do not support an arbitrary cut-off between the two disorders.

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PubMed2006

Insomnia in Parkinson's disease: frequency and progression over time.

OBJECTIVES: To examine the development of nocturnal sleeping problems in patients with Parkinson's disease (PD) over an 8-year period and to study the clinical and demographic correlates of insomnia. METHODS: 231 patients were included in a population-based prevalence study in 1993, and re-examined in 1997 and 2001. At all study visits, we applied semi-structured interviews to obtain information on clinical and demographic data, as well as on nocturnal sleeping problems. Standardised rating scales of parkinsonism, depression and cognitive impairment were used. The relationship between insomnia and demographic and clinical variables was analysed using population-averaged logistic regression models for correlated data. 231 patients were included at baseline, 142 were available for re-evaluation in 1997 and 89 patients in 2001. RESULTS: Most nocturnal sleeping problems varied little in prevalence over time, whereas problems related to turning in bed and vivid dreaming or nightmares increased. Insomnia was present in 54-60% of the patients at each of the three study visits and varied considerably in individual patients over time. The presence of insomnia was closely related to disease duration, higher Montgomery-Asberg Depression Rating Scale scores and female sex. CONCLUSION: Insomnia is a highly frequent complaint in patients with PD. It fluctuates over time in individual patients, and its origin seems to be multifactorial. Physicians should be aware of the high prevalence of insomnia in patients with PD and should examine their patients for a possible coexisting depression.

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PubMed2006

Excessive daytime sleepiness in Parkinson disease: is it the drugs or the disease?

OBJECTIVE: To examine associated demographic and clinical correlates and the development of excessive daytime sleepiness (EDS) over 8 years in a community-based cohort of patients with Parkinson disease (PD). METHODS: A total of 232 patients with PD were included in a population-based prevalence study in 1993. Patients were followed prospectively and reexamined after 4 and 8 years. At all study visits, the authors administered semistructured interviews to obtain information on clinical and demographic variables. Standardized rating scales of parkinsonism, depression, and cognitive impairment were used. The diagnosis of EDS was based on a sleep questionnaire and in 2001 also on the Epworth Sleepiness Scale. Population-averaged logistic regression models for correlated data were performed to study the relationship between EDS and various demographic and clinical variables. RESULTS: Of the 232 patients included at baseline, 138 were available for re-evaluation after 4 years and 89 patients after 8 years. Frequency rates of EDS increased from 5.6% in 1993 to 22.5% in 1997 and 40.8% in 2001, with an 8-year prevalence of 54.2%. In the majority of patients, EDS was a persistent feature. In the logistic regression model, EDS was related to age, gender, and use of dopamine agonists. In those never having used dopamine agonists, hypersomnia was associated with the Hoehn and Yahr stage only. CONCLUSION: Excessive daytime sleepiness is a frequent and highly persistent feature in Parkinson disease, with multifactorial underlying pathophysiology. The authors' findings indicate that both age and disease related disturbances of the sleep-wake regulation contribute to hypersomnia in PD. Treatment with dopamine agonists also contributed to excessive daytime sleepiness in our patients.

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PubMed2006

Review of the therapeutic management of Parkinson's disease. Report of a joint task force of the European Federation of Neurological Societies and the Movement Disorder Society-European Section. Part I: early (uncomplicated) Parkinson's disease.

The aim of the study was to provide evidence-based recommendations for the management of early (uncomplicated) Parkinson's disease (PD), based on a review of the literature. Uncomplicated PD refers to patients suffering from the classical motor syndrome of PD only, without treatment-induced motor complications and without neuropsychiatric or autonomic problems. MEDLINE, Cochrane Library and International Network of Agencies for Health Technology Assessment (INAHTA) database literature searches were conducted. National guidelines were requested from all European Federation of Neurological Societies (EFNS) societies. Non-European guidelines were searched for using MEDLINE. Part I of the guidelines deals with prevention of disease progression, symptomatic treatment of motor features (parkinsonism), and prevention of motor and neuropsychiatric complications of therapy. For each topic, a list of therapeutic interventions is provided, including classification of evidence. Following this, recommendations for management are given, alongside ratings of efficacy. Classifications of evidence and ratings of efficacy are made according to EFNS guidance. In cases where there is insufficient scientific evidence, a consensus statement (good practice point) is made.

Antiparkinson Agents↗

PubMed2006

Review of the therapeutic management of Parkinson's disease. Report of a joint task force of the European Federation of Neurological Societies (EFNS) and the Movement Disorder Society-European Section (MDS-ES). Part II: late (complicated) Parkinson's disease.

To provide evidence-based recommendations for the management of late (complicated) Parkinson's disease (PD), based on a review of the literature. Complicated PD refers to patients suffering from the classical motor syndrome of PD along with other motor or non-motor complications, either disease-related (e.g. freezing) or treatment-related (e.g. dyskinesias or hallucinations). MEDLINE, Cochrane Library and INAHTA database literature searches were conducted. National guidelines were requested from all EFNS societies. Non-European guidelines were searched for using MEDLINE. Part II of the guidelines deals with treatment of motor and neuropsychiatric complications and autonomic disturbances. For each topic, a list of therapeutic interventions is provided, including classification of evidence. Following this, recommendations for management are given, alongside ratings of efficacy. Classifications of evidence and ratings of efficacy are made according to EFNS guidance. In cases where there is insufficient scientific evidence, a consensus statement ('good practice point') is made.

Antiparkinson Agents↗

PubMed2006

Parkin gene variations in late-onset Parkinson's disease: comparison between Norwegian and German cohorts.

OBJECTIVES: Mutations in the Parkin gene can cause autosomal recessive early-onset Parkinson's disease (PD). Recently, Parkin mutations were also suggested to play a role in the commoner late-onset forms of PD. METHODS: We compared a German cohort of PD patients (95) with a Norwegian cohort of PD patients (96). Both cohorts have predominant late-onset form of PD. Mutation and polymorphism frequencies were compared via single-strand conformation polymorphism and sequence analyses. RESULTS: Three heterozygous missense mutations (Arg256Cys, Arg402Cys and Thr240Met) were found in late-onset PD patients in the German patient cohort (1.6%). A missense mutation (Arg402Cys) was also found in one of 149 healthy control subjects (0.3%). Only one heterozygous missense mutation (Arg256Cys) was identified in a Norwegian patient suffering from late-onset PD (0.5%). The frequencies of four known single nucleotide polymorphisms significantly differ between the two distant European populations. CONCLUSION: The results support the hypothesis that heterozygous mutations in the Parkin gene may act as susceptibility alleles for late-onset forms of PD in rare cases.

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PubMed2006

Drug costs for patients with Parkinson's disease in two different European countries.

OBJECTIVE: To examine factors that influence drug costs in patients with Parkinson's disease (PD) and to compare the costs in two different countries. METHODS: We examined drug costs among 438 patients with PD (286 from Germany and 152 from Norway) and collected information on the patients' age, medication, disease duration, and Hoehn & Yahr stage. RESULTS: Drug expenses rose with increasing severity and duration of the disease. This increase differed somewhat between the two countries. Mean drug costs per day and patient in the German group was Euro 5.78 while it was Euro 3.92 in the Norwegian group. A higher proportion of the German patients were treated with two or more drugs, and the switch from mono- to multi-drug therapy was done earlier in the course of the disease. Dopamine agonists caused 44% of total drug costs in both countries. CONCLUSION: Different management strategies of PD have a great impact on drug costs. Surveillance of prescription habits and careful cost/benefit analyses are therefore important.

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PubMed2005

IL-10 promoter haplotype influence on interferon treatment response in multiple sclerosis.

The level of interleukin-10 (IL-10) expression is related to polymorphisms -1082 (G/A), -819 (T/C) and -592 (A/C) in the promoter region of the IL-10 gene, which constitute three haplotypes, GCC, ATA, and ACC. The ATA (a non-GCC) haplotype, which is associated with low IL-10 expression, has been shown to improve interferon (IFN) treatment response in hepatitis C. We analysed the distribution of IL-10 promoter haplotype combinations to determine whether they could influence initial IFN treatment response in 63 patients with relapsing-remitting multiple sclerosis (MS). The patients were grouped into non-GCC or GCC haplotypes, and the clinical and magnetic resonance imaging (MRI) disease activity was compared in the two groups. During the first 6 months of treatment, MS patients with non-GCC haplotypes experienced fewer new MRI T1-contrast enhancing lesions [0.77+/-0.36 (SEM)] than patients with the GCC haplotype (2.45+/-0.57) (P=0.05, Mann-Whitney U test). No differences were detected on clinical disease activity. The results suggest an influence of IL-10 promoter polymorphisms on IFN treatment response in MS.

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PubMed2005

The influence of cerebrovascular risk factors on incident dementia in patients with Parkinson's disease.

OBJECTIVE: To examine if risk factors for cerebrovascular disease would increase the risk for dementia in patients with Parkinson's disease (PD). METHODS: Non-demented patients were recruited from an epidemiological study of PD in the county of Rogaland, Norway. PD and dementia were diagnosed according to strict diagnostic criteria. Established cerebrovascular risk factors were recorded at baseline, and their influence on incident dementia was assessed 4 years later using logistic regression analysis. RESULTS: A total of 171 non-demented PD patients constituted the at-risk population. Seventy-two (55%) had at least one cerebrovascular risk factor. A total of 130 subjects (96% of survivors) completed the follow-up examination. Forty-three (33%) new cases of dementia were found. Twenty-five of the 72 (35%) patients with and 18 of the 58 (31%) subjects without any risk factor developed dementia (ns). A significant association with dementia was found for a diagnosis of heart failure in the univariate analyses. However, in the logistic regression analysis none of the cerebrovascular risk factors were significantly associated with incident dementia. CONCLUSIONS: In this large and representative cohort of patients with PD cerebrovascular risk factors were not associated with incident dementia, indicating that the disease-related degenerative brain changes are the main causes of dementia in PD.

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PubMed2005

Neuropsychiatric disturbances in Parkinson's disease clusters in five groups with different prevalence of dementia.

OBJECTIVE: To investigate the inter-relationship of neuropsychiatric disturbances in Parkinson's disease (PD) by cluster analysis and describe the properties of the clusters. METHOD: A total of 139 patients were assessed using the neuropsychiatric inventory (NPI). A cluster-analysis was used to investigate the inter-relationship of NPI items. The clusters were profiled regarding dementia (PDD) and major depression. RESULTS: A total of 39 patients showed no neuropsychiatric symptoms. The remaining 100 patients (43% PDD) were divided in to five clusters. The largest group (42, 31% PDD) showed symptoms of mild depression, followed by a group (29, 79.3% PDD) with hallucinations and mild other symptoms. The third group (14, 7.1% PDD) had sleep disturbances exclusively. The fourth group (8, 25% PDD) showed apathy, anxiety and depression. The smallest group (7, 57.1% PDD) had high scores on several NPI items. CONCLUSION: Our PD sample can be divided in to clusters based on the NPI, with different prevalence of dementia and depression.

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PubMed2005

Neuropsychiatric symptoms in patients with multiple sclerosis.

OBJECTIVE: To explore the range of psychiatric symptoms in patients with multiple sclerosis (MS) and their association with neurological disability. METHOD: Patients diagnosed with MS during 1998-2000 in Rogaland and Hordaland counties, western Norway, were included. Psychiatric symptoms were assessed by the Neuropsychiatric Inventory (NPI). Patients with systemic lupus erythematosus (SLE) served as controls. RESULTS: Eighty-six of 93 eligible MS patients were included, and 80% showed at least one psychiatric symptom. The most frequent symptoms were depression (59%), sleep disturbance (48%), irritability/emotional lability (42%), and apathy (31%). Depression was associated with higher disability score. MS patients showed significantly higher NPI irritability score (P = 0.002), appetite disturbance score (P < 0.001), and apathy score (P = 0.01) than SLE patients. CONCLUSION: Neuropsychiatric symptoms occur frequently in patients with MS. Irritability and apathy are independent of disability and chronic disease and represent unique disease manifestations.

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PubMed2004

Is fatigue an independent and persistent symptom in patients with Parkinson disease?

OBJECTIVE: To evaluate if mental fatigue is a symptom that appears independently from other clinical features in patients with Parkinson disease (PD), and to study if fatigue is persistent over time in these patients. METHODS: In 1993, 233 patients with PD were included in a community-based study of fatigue and followed prospectively over 8 years. Fatigue was measured by a combination of a seven-point scale and parts of the Nottingham Health Profile (NHP) at baseline and after 4 and 8 years. In addition, the Fatigue Severity Scale (FSS) was used to evaluate fatigue in 2001. Population-averaged logistic regression models for correlated data were performed to study the relationship between fatigue and various demographic and clinical variables. RESULTS: In patients who were followed throughout the 8-year study period, fatigue increased from 35.7% in 1993 to 42.9% in 1997 and 55.7% in 2001. Fatigue was related to disease progression, depression, and excessive daytime sleepiness (EDS). However, the prevalence of fatigue in patients without depression and EDS remained high and increased from 32.1% to 38.9% during the study period. For about 44% of the patients with fatigue the presence of this symptom varied during the study period, as it was persistent in 56% of the patients with fatigue. CONCLUSIONS: The authors confirmed the high prevalence of mental fatigue in patients with Parkinson disease (PD). Fatigue is related to other non-motor features such as depression and excessive daytime sleepiness, but cannot be explained by this comorbidity alone. In more than half of the patients mental fatigue is persistent and seems to be an independent symptom that develops parallel to the progressive neurodegenerative disorder of PD.

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PubMed2003

Cognitive, psychiatric and motor response to galantamine in Parkinson's disease with dementia.

BACKGROUND: Cholinesterase inhibitors with additional nicotinic activity, such as galantamine, may be useful in PD patients with dementia (PDD) since stimulation of nicotinic receptors may prevent the down-regulation that is likely to accompany cholinesterase inhibition and facilitate dopamine release in the striatum. METHODS: Sixteen PDD patients (six female) with onset of cognitive impairment after at least one year with parkinsonism participated in this open-label trial of galantamine. Cognitive, psychiatric, and motor symptoms were assessed before and after 8 weeks of treatment with galantamine using unstructured clinical assessment as well as rating scales including the Mini-Mental State Examination (MMSE), clock drawing test, verbal fluency and selected items from the Neuropsychiatric Inventory (NPI). RESULTS: Age (mean, SD) was 75.6 (5.2) years, duration of PD 13.4 (5.9), duration of dementia 2.1 (1.7) years, Hoehn and Yahr score was 3.8 (0.8) and baseline MMSE score was 17.7 (6.7). Side-effects caused discontinuation in three patients, but were rare and mild in the remaining 13. Improvement of global mental symptoms was noted in eight patients, whereas worsening was reported in four. Hallucinations improved in seven of the nine patients with hallucinations before treatment. Parkinsonism improved in six patients, but a mild worsening of tremor was noted in three. Clock-drawing improved (p=0.016), and trends towards improvement on MMSE (p=0.09) and verbal fluency (p=0.16) were found. CONCLUSIONS: Although controlled trials are needed, the findings suggest that galantamine is useful in patients with PDD.

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PubMed2003

The influence of fatigue on health-related quality of life in patients with Parkinson's disease.

OBJECTIVE: To examine the correlation between fatigue and health-related quality of life (HRQL) in patients with Parkinson's disease (PD). PATIENTS AND METHODS: Sixty-six patients with idiopathic PD. The patients did not have a depressive mood disorder or cognitive impairment. Fatigue was measured by the Fatigue Severity Scale (FSS). HRQL was measured by the Parkinson's Disease Questionnaire (PDQ-39) and the Short-Form 36 (SF-36). RESULTS: Thirty-three (50%) of the patients had significant fatigue. Patients with fatigue had a more advanced disease than those without fatigue, measured by the UPDRS scale, including a higher Hoehn and Yahr stage and lower Schwab and England score. Patients with fatigue reported more distress in the dimensions of emotional well-being and mobility (PDQ-39) and also had a significantly higher PDQ summary index. On the SF-36 patients with fatigue reported more problems in the areas of physical functioning, role limitation (physical), social functioning and vitality. Correlations between the FSS and the HRQL scales were highest for the summary index of PDQ-39 and in the dimensions of ADL, mobility and emotional well-being (PDQ-39) and physical functioning, role limitation (physical), social functioning, general health and vitality (SF-36). CONCLUSIONS: PD has a substantial negative impact on HRQL. We found a strong correlation between fatigue and high distress scores on HRQL scales in a population of patients with PD who were not depressed or demented. The diversity of symptoms and high prevalence of non-motor features, including fatigue, is important to take into account in our efforts to optimize treatment and care for this patient group.

Activities of Daily Living↗

PubMed2003

Familial Parkinson's disease: a community-based study.

Genetic factors seem to be important in the pathogenesis of Parkinson's disease (PD). It is however, still controversial whether these factors also are reflected in a familial aggregation of PD. The aim of this study was to investigate the frequency of PD patients with a positive PD family history compared with two control groups. The included 245 PD patients were examined by neurologists and information was obtained through a semi-structured interview. The patients and the control groups were examined for the frequency of PD and dementia in their families. The 245 patients with PD were included in this study. A positive PD-family history could be obtained in 53 (21.6%) patients. The frequency was three- and four-fold increased as compared with the control groups (P < 0.001). Age at onset of disease was not different among patients with and without PD in the family. The frequency of dementia did not differ in the family of individuals with and without PD (P > 0.1). As a conclusion our study of PD in a community based population supports previous reports of a three- to fourfold increased risk for PD in the families of patients with the disease. Our results indicate that the familial aggregation of the disease is independent of the age of the proband.

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PubMed2003

The tolerability and efficacy of entacapone over 3 years in patients with Parkinson's disease.

The long-term safety and efficacy of the catechol-O-methyltransferase (COMT) inhibitor entacapone was investigated in a 3-year open-label extension of the 6-month double-blind placebo-controlled Nordic (NOMECOMT) study. After a wash-out following this study, 132 patients with Parkinson's disease (PD) experiencing motor fluctuations treated with levodopa/dopa decarboxylase (DDC) inhibitor received additional therapy with entacapone 200 mg, administered with each dose of levodopa. The most common adverse events (AEs) were insomnia (30%), dizziness (20%), nausea (20%), aggravated parkinsonism (17%) and hallucinations (14%). Only 19 (14%) patients discontinued because of AEs. Most dopaminergic AEs occurred shortly after initiation of entacapone, and these could be managed by levodopa down-adjustment. The mean duration of benefit of a single dose of levodopa increased significantly from 2.1 to 2.8 h (P < 0.01) at 3 months and remained prolonged for the whole study. At the end of the study, the mean daily dose of levodopa was significantly decreased from baseline (from 737 to 696 mg; P < 0.05). The patients' global assessment indicated that 69% of patients improved when given entacapone and this proportion was maintained until the end of the study (64%). There was a significant worsening of disability upon withdrawal of entacapone. In conclusion, entacapone given in combination with levodopa, has a good long-term safety profile and a sustained beneficial effect in patients with PD with motor fluctuations.

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PubMed2003

Performance on the dementia rating scale in Parkinson's disease with dementia and dementia with Lewy bodies: comparison with progressive supranuclear palsy and Alzheimer's disease.

BACKGROUND: The relation between dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD) is unknown. OBJECTIVES: To compare the cognitive profiles of patients with DLB and PDD, and compare those with the performance of patients with a subcortical dementia (progressive supranuclear palsy) and a cortical dementia (Alzheimer's disease). DESIGN: Survey of cognitive features. SETTING: General community in Rogaland county, Norway, and a university dementia and movement disorder research centre in the USA. PATIENTS: 60 patients with DLB, 35 with PDD, 49 with progressive supranuclear palsy, and 29 with Alzheimer's disease, diagnosed by either standardised clinical procedures and criteria (all PDD and Alzheimer cases and 76% of cases of progressive supranuclear palsy), or necropsy (all DLB cases and 24% of cases of progressive supranuclear palsy). Level of dementia severity was matched using the total score on the dementia rating scale adjusted for age and education. MAIN OUTCOME MEASURES: Dementia rating scale subscores corrected for age. RESULTS: No significant differences between the dementia rating scale subscores in the PDD and DLB groups were found in the severely demented patients; in patients with mild to moderate dementia the conceptualisation subscore was higher in PDD than in DLB (p = 0.03). Compared with Alzheimer's disease, PDD and DLB had higher memory subscores (p < 0.001) but lower initiation and perseveration (p = 0.008 and p=0.021) and construction subscores (p = 0.009 and p = 0.001). DLB patients had a lower conceptualisation subscore (p = 0.004). Compared with progressive supranuclear palsy, PDD and DLB patients had lower memory subscores (p < 0.001). CONCLUSIONS: The cognitive profiles of patients with DLB and PDD were similar, but they differed from those of patients with Alzheimer's disease and progressive supranuclear palsy. The cognitive pattern in DLB and PDD probably reflects the superimposition of subcortical deficits upon deficits typically associated with Alzheimer's disease.

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PubMed2002

Development of daytime somnolence over time in Parkinson's disease.

The authors examined the development over time of excessive daytime sleepiness (EDS) in patients with PD by evaluating EDS among 142 patients in 1993 and 4 years later. Eleven patients were diagnosed with EDS in 1993. In all of these patients, EDS persisted 4 years later. During follow-up, 30 new patients had EDS (6% new patients per year). In 1997, 29% of the patients with PD had EDS. The development of EDS correlated with more advanced disease and dementia.

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