Publications (119)429.28 Total impact
- [Show abstract] [Hide abstract] ABSTRACT: Stimulation of the subthalamic nucleus (STN-DBS) is an established treatment with long-term beneficial effects on motor symptoms in patients with Parkinson's disease (PD). The long-term development of non-motor problems after STN-DBS is not fully understood. In this study, we have studied how non-motor problems develop in patients with and without STN-DBS. We collected data from a prospectively followed cohort of patients that had been operated with STN-DBS 6-9 years before final examination and compared our findings to the longitudinal development of non-motor problems in a non-operated, comparable reference population. In general, the non-motor problems of advanced PD seem to develop independently of treatment with STN-DBS. We found that depressions do not worsen after STN-DBS, and the Montgomery and Aasberg Depression Rating Scale score in operated patients was substantially reduced from pre-operatively to post-operatively. Further, fatigue may represent an important unrecognized side effect of long-term stimulation, as fatigue was found to increase rapidly in operated patients already a year after surgery and continued to increase trough the 6- to 9-year follow-up. The non-motor problems of advanced PD seem to develop independently of treatment with STN-DBS. This may influence the strategy for choice of when to perform this therapy for eligible patients. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
- [Show abstract] [Hide abstract] ABSTRACT: Introduction: Freezing of gait (FOG) is a potentially disabling motor problem in Parkinson's disease (PD) with uncertain etiology. Longitudinal studies of FOG in PD are scarce. We determined the prevalence, incidence, and associated clinical risk factors and concomitants of FOG during prospective long-term follow-up of a population-based PD cohort. Methods: A community-based prevalent cohort of 232 PD patients was followed prospectively over 12 years. Reassessments were conducted at 4 and 8 years, and then annually. FOG, as well as severity of parkinsonism, motor complications, and psychotic symptoms were assessed by the Unified PD Rating Scale, and cognitive impairment by the Mini-Mental State Examination. Generalized estimating equations were applied to investigate baseline risk factors and concomitants of FOG over time. Results: The point prevalence of FOG at baseline was 27% (95% confidence interval (95%-CI) 22-33%). By study end, 63% (95%-CI 56-69%) of patients had developed FOG. The incidence rate of FOG was 124.2 (95%-CI 101.5-152.1) per 1000 person-years. Motor fluctuations (odds ratio (OR) 3.45; p = 0.036) and higher levodopa dose (OR 1.30/100 mg, p = 0.009) at baseline were independent risk factors of incident FOG. Prevalent FOG over time was additionally associated with features thought to reflect extrastrial, non-dopaminergic pathologies, including PIGD (postural instability/gait difficulty, OR 6.30/10 points, p < 0.001) and psychosis (OR 1.85; p = 0.016). Conclusion: These findings demonstrate that FOG affects the majority of patients in the general PD population and provide support to the hypothesis that alterations in both basal ganglia and extrastriatal brain areas are involved in the pathogenesis of FOG in PD.
- [Show abstract] [Hide abstract] ABSTRACT: Objectives Stimulation of the subthalamic nucleus (STN-DBS) is an established treatment with long-term beneficial effects on motor symptoms in patients with Parkinson's disease (PD). The efficacy of STN-DBS on non-dopaminergic motor symptoms remains less elucidated. In this study, we have examined short- and long-term impacts of STN-DBS on the development of the postural instability and gait difficulties (PIGD) phenotype, freezing of gait (FOG), and falls.Materials and methodsWe collected data from a prospectively followed cohort of patients that had been operated with STN-DBS 6–9 years before final examination and compared our findings to the longitudinal development of the same symptoms in a non-operated, historical reference population.ResultsDuring short-term follow-up after surgery, we observed a marked improvement in mean UPDRS-motor score from 27 to 18. We also found clear improvements in tremor, bradykinesia, rigidity, and PIGD scores. However, 6–9 years after surgery, all patients had a dominating PIGD pattern of parkinsonism and 50% of the patients had developed FOG and/or had become recurrent fallers. The disease development in a group of patients with PD from the presurgery period had a similar trajectory as among the operated patients. In addition, mean annual change of both bradykinesia and PIGD scores was nearly identical in both study groups while tremor and rigidity had a significant better development in the operated patients.Conclusions We found that STN-DBS induces an acute improvement of PIGD symptoms. The following long-term development was however characterized by a marked progression of non-dopaminergic symptoms.
- [Show abstract] [Hide abstract] ABSTRACT: Treatment for Parkinson's disease (PD) is symptomatic. Surgical treatment with continuous high-frequency stimulation of the subthalamic nucleus (STN-DBS) is established as a safe symptomatic treatment with long-term beneficial effects. It has been postulated that STN-DBS could halt the progression of PD through a disease modifying or neuroprotective effect. To investigate the postulated disease modifying or neuroprotective effect of STN-DBS by comparing the rate of deterioration of parkinsonism and mortality over time in two selected and matched groups of patients with PD with and without surgery. Group A was derived from all patients who received STN-DSB surgery at Oslo University Hospital, from January 2001 to December 2007. Group B was derived from a prevalence study of PD in the Stavanger area of Western Norway in 1993. The two groups were individually matched and the disease progression measured by Unified Parkinson's Disease Rating Scale-motor scores, and the mortality was compared. The mean annual change based on baseline and last observation scores in individually matched groups was 0.97 (SD = 3.57) for the surgery group and 1.04 (SD = 3.33) for the controls and thus not significantly different, F(1, 104) = .21, P = 0.89. The long-term mortality was also similar in the two groups during long-term follow-up, hazard ratio = 1.76, CL 0.91-3.40, P = 0.091. This study gives no support to a postulated disease modifying or neuroprotective effect of STN-DBS in patients with PD.
- [Show abstract] [Hide abstract] ABSTRACT: To describe a representative population of patients recently diagnosed with MS in terms of both motor and non-motor disability. In particular we wanted to examine the HRQoL in this population to get a better understanding of what impact various clinical features have on the patients’ experience of distress in the early phase of the disease. Ninety three patients diagnosed with MS in Hordaland and Rogaland county in 1998–2000 and 96 healthy controls were examined through questionnaires on HRQoL (SF-36), depression (Beck's depression inventory), fatigue (fatigue severity scale) and apathy (Starkstein's apathy scale). The patients also underwent neurological examination including the expanded disability status scale and the Multiple Sclerosis Functional Composite, as well as the symbol digit memory test and the selective reminder test. Patients with MS reported a lower HRQoL than the controls with a mean physical health summary score of 57.3 compared to 84.5 (P < 0.001), and a mental health summary score of 66.4 vs 79.2 (P < 0.001). The controls scored significantly higher on all SF-36 sub scores except for bodily pain. The incidence of fatigue was 71% in patients compared to 27% in controls (P < 0.001), whereas 46% of patients vs 18% of controls reported depression (P < 0.001). The mean score for apathy was significantly higher among patients. Patients with recently diagnosed MS reported significantly lower on both physical and mental aspects of HRQoL compared with controls. Depression, fatigue and apathy were more common and more severe in MS. We found no correlation between cognitive decline and HRQoL scores.
- [Show abstract] [Hide abstract] ABSTRACT: Objectives Autonomic symptoms are present in early stages of Parkinson's disease (PD), but evidence on how they are influenced by dopaminergic treatment remains unclear. The aim of this study was to investigate the impact of dopaminergic treatment on autonomic symptoms in early PD in a population-based cohort. MethodsA total of 171 drug-naive patients with PD were investigated at diagnosis and 12 months later. Orthostatic blood pressure was measured, and autonomic symptoms were assessed by a preliminary version of the Movement Disorders Society-sponsored new version of the Unified Parkinson's Disease Rating Scale (range 0–4). ResultsIn the 82% using dopaminergic treatment after 1 year, constipation and orthostatic blood pressure drop increased. There was a tendency towards increased orthostatic dizziness and urinary dysfunction. Dysphagia scores were reduced, and this was associated with higher levodopa-equivalent daily dose. Conclusions Dopaminergic treatment during the first year after initiation seems to have only a minor impact on autonomic symptoms in early PD. It may increase constipation and orthostatic dizziness, while dysphagia can improve. Autonomic symptoms remained mild after 1 year of dopaminergic treatment.
- [Show abstract] [Hide abstract] ABSTRACT: Objectives: There are limited data on treatment effect in early and drug-naïve Parkinson's disease (PD) outside of clinical trials. We sought to review the treatment effects on motor symptoms in early, unselected PD patients. Methods: We included 183 drug-naïve patients from a longitudinal cohort (The Norwegian ParkWest study). At the time of diagnosis, motor symptoms were assessed and rated. Treatment was unrestricted, aimed at treating each patient optimally. Patients were reassessed after 12 months, and then grouped according to treatment: No dopaminergic treatment (NDT), dopamine agonists (DA) or levodopa. All strategies could be combined with monoamine oxidase B inhibitors. Results: In general, the chosen treatment was coherent with current practice. During follow-up, patients given NDT (n = 40) had unaltered clinical motor symptoms, as opposed to improvement in the DA- and levodopa-treated patients (n = 140). The overall improvement in these two groups was fairly similar, but axial symptoms did not improve in levodopa-treated patients as opposed to the younger DA-treated patients. Conclusions: Twelve months after the diagnosis, motor symptoms in approximately one-fifth of PD patients remained clinically stable. Tremor, bradykinesia and rigidity improved in the dopaminergic-treated patients. Axial symptoms were more treatment resistant, and the different symptomatic effects found between treatment strategies may be age related.
- [Show abstract] [Hide abstract] ABSTRACT: Parkinson's disease (PD) may be associated with a number of different diseases due to common risk factors or overlapping symptomatology. We have asked for possible associated disorders in a Norwegian population of incident PD patients and controls, the Norwegian ParkWest study. The patients were diagnosed according to the Gelb criteria. 212 incident PD patients and 175 age and gender matched controls were included. PD patients and controls were asked for information on earlier medical history and family history. PD patients had a higher frequency of self-reported symptoms of depression (p = 0.003) and anxiety disorders (p = 0.004) before baseline. They tended to have a higher frequency of diabetes (p = 0.09) and had a higher frequency of prior stroke or TIA (p = 0.004).
- [Show abstract] [Hide abstract] ABSTRACT: To examine the frequencies and clinical characteristics of fallers and non-fallers at different stages of Parkinson's disease (PD). The sample consisted of 232 patients in an unselected cross-sectional cohort of patients with PD, 207 newly diagnosed and drug naive patients and 175 controls. The examinations included the Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn and Yahr, Schwab and England, and Mini-Mental State Examination. According to item 13 of the UPDRS, the participants were classified as fallers, rare-fallers and non-fallers. In the cross-sectional study cohort, 19% of the patients were classified as fallers and 25% as rare-fallers. Higher scores on activity of daily living (UPDRS ADL score) and motor complications (UPDRS complication of therapy score) were significantly and independently associated with falling. In the cohort of newly diagnosed patients with PD 2% were classified as fallers and 15% as rare-fallers. In the age- and sex-matched control group, none were fallers, and only 2% were rare-fallers. Patients with tremor-dominated PD subtype in both study populations did not fall. Falls are a markedly increasing problem in patients with PD as the disease progresses. Healthcare workers should ask patients about falling, and specially focus on patients with motor complications or postural instability and gait disability-dominated subtype of parkinsonism.
- [Show abstract] [Hide abstract] ABSTRACT: Sleep problems are common in Parkinson's disease (PD) and increasingly so with disease progression. The frequency of these problems and the influence of dopaminergic treatment on sleep in early stages of PD remain unclear. We have therefore in this study examined the subjective experience of sleep problems in drug-naïve patients with early PD and how these problems developed after 1 year on dopaminergic treatment using the Parkinson's Disease Sleep Scale (PDSS). In all, 138 drug-naïve patients with early PD derived from a population-based incident cohort and 138 age- and gender-matched control subjects were thoroughly assessed for Parkinsonism, cognition, depressive symptoms and sleep by structured interviews and clinical examination at the time of diagnosis and 1 year later on medication. Sleep problems were assessed using the PDSS. The total PDSS score for patients with PD was lower compared with controls, 119 vs. 127 (P < 0.05) at baseline and 121 vs. 128 (P < 0.005) after 1 year on drugs. Analyses of PDSS subdomains showed more nocturnal motor off symptoms both at baseline and after 1 year (P < 0.005) and increased daytime somnolence in patients compared with control subjects (P < 0.005 at baseline and P < 0.05 after 1 year). Only minor changes in sleep scores were seen after the introduction of dopaminergic treatment. Patients with early PD report only modestly increased subjective sleep problems at the time of diagnosis compared with control subjects and dopaminergic treatment during the first year in general only slightly changed the experienced sleep problems.
- [Show abstract] [Hide abstract] ABSTRACT: Although fatigue is recognized as a common and debilitating symptom in patients with Parkinson's disease (PD), little is known on how and when this symptom emerges during disease progression. The aim of the study was to explore the presence and severity of fatigue in patients with PD at the time of diagnosis, before dopaminergic treatment has been instituted. The present study is part of the Norwegian ParkWest project, a large cohort study of patients with incident PD in Norway. PD was diagnosed according to the Gelb criteria. The study population comprised 199 patients with untreated, newly diagnosed PD and 172 control subjects, matched for gender and age. Fatigue was measured by the Fatigue Severity Scale (FSS). Fifty-five percent of the patients with PD had clinical significant fatigue (FSS > 4), compared with about 20% of the controls (RR = 2.9). The mean score in patients on the FSS was 4.4 (SD 1.7) and in controls 3.1 (SD 1.3). In addition, there were highly significant differences between patients and controls in each of the nine FSS items. In a regression analysis, only the Montgomery and Åsberg Depression Rating Scale and Unified Parkinson's Disease Rating Scale-Activities of Daily Living scores were significantly associated with fatigue. There was no correlation between fatigue and cognitive impairment and hypersomnia. Fatigue is a common symptom in PD, also in patients with early, untreated disease, and it has a negative impact on these patients' activity of daily living. Also in early PD, fatigue is an important consideration in the management of patients with the disease.
- [Show abstract] [Hide abstract] ABSTRACT: This study explores the risk and correlates of leg restlessness in drug-naive patients with Parkinson disease (PD) as compared to control subjects matched for age and gender. A total of 200 drug-naive patients with early, unmedicated PD derived from a population-based incident cohort and 173 age- and gender-matched control subjects were assessed for leg restlessness by structured interviews, clinical examination, and blood samples. All subjects were Caucasian. Restless legs syndrome (RLS) was diagnosed according to the essential diagnostic criteria. More patients (81 of 200, 40.5%) than controls (31 of 173, 17.9%) reported leg restlessness (p < 0.001). Thirty-one (15.5%) of these patients with PD and 16 (9.2%) control subjects met RLS criteria (p = 0.07). A total of 21 (12.5%) patients and 12 (6.9%) controls with RLS remained after the exclusion of potential RLS mimics and 26 patients vs 10 control subjects with leg motor restlessness (LMR), leading to a relative risk for RLS of 1.76 (95% confidence interval [CI] 0.90-3.43, p = 0.089) and 2.84 for LMR (95% CI 1.43-5.61, p = 0.001) in PD. Except for increased sleep disturbances in patients with RLS and increased Montgomery and Åsberg Depression Rating Scale scores for patients with RLS or LMR there were no other major differences in relevant blood tests, motor or cognitive function between PD with and without RLS or LMR. LMR and not RLS occurs with a near 3-fold higher risk as compared to controls in early PD. The findings underline a need for more accurate assessments of RLS in PD and support the notion that RLS and PD are different entities.
- [Show abstract] [Hide abstract] ABSTRACT: To assess the effect of tolcapone added to levodopa plus benserazide or carbidopa on the “wearing-off” phenomenon in patients with Parkinson's disease, we undertook a double-blind, randomized, placebo-controlled, parallel-group study of tolcapone 50, 200, or 400 mg three times daily (t.i.d.) for 6 weeks in addition to levodopa therapy. We studied 154 parkinsonian patients, aged 40 years or more, who presented with the “wearing-off” phenomenon despite “optimal” antiparkinsonian therapy. The main outcome measures were “on”- and “off”-time, Investigator's Global Assessments, Subscales of the Unified Parkinson's Disease Rating Scale, changes in levodopa dosage, and safety and tolerability. Tolcapone was more effective than placebo in reducing the “wearing-off” phenomenon between baseline and week 6 at all three dosages. Tolcapone 200 mg t.i.d. increased “on”-time from 37.9% of the waking day to 50.8% (p < 0.01) and reduced “off”-time from 26.7% of the waking day to 16.4% (p < 0.05). Tolcapone treatment was generally well tolerated at all dosages. Initial exacerbation of adverse dopaminergic effects was controlled by levodopa dosage adjustment; at week 6, the mean total daily levodopa dosage had decreased by 80 mg, from 694 mg at baseline, in the tolcapone 200 mg t.i.d. group (p < 0.01). We conclude that the addition of tolcapone to levodopa plus a decarboxylase inhibitor effectively and safely reduces the “wearing-off” phenomenon in parkinsonian patients.
- [Show abstract] [Hide abstract] ABSTRACT: Objectives: Apolipoprotein E (APOE) gene alleles have been associated with various neurodegenerative disorders. However, there have been conflicting reports on associations between APOE alleles and Parkinson's disease (PD) and age at onset in PD. There exist no data on APOE alleles in an unselected cohort of patients with incident PD. Patients and methods: To determine the role of APOE alleles in PD and age of onset in PD at time of diagnosis, 203 patients with incident PD and 187 healthy control subjects from Western and Southern Norway were investigated according to their APOE allele status. Results: No association was observed between any APOE alleles and susceptibility to PD or age at onset in PD. Conclusion: In our cohort of unselected, incident PD patients APOE alleles do not seem to play a role for development of PD. Prospective, long-term follow-up may still reveal associations between APOE alleles and clinical and neuropsychological progression in PD.
- [Show abstract] [Hide abstract] ABSTRACT: To be treated for cancer must be a frightening experience. Yet quality of life (QoL) of successfully treated cancer patients seems to be relatively similar in comparison with QoL of a general population, with psychological coping partly responsible for this finding. When measuring choice of coping, the nature of coping score levels constituting appropriate scores, and whether score levels rely on the context of the disease has not been settled. We have studied the COPE coping responses as related to disease in successfully treated head and neck squamous cell carcinoma (HNSCC) patient groups (general and laryngectomized), as well as compared to multiple sclerosis (MS) patients. The COPE response patterns have also been compared to the Beck depression inventory (BDI) scores. Age and gender of patients were not directly associated with choice of coping. Within the problem-focused coping indexes, the coping index "active coping" was reported to be most utilized among HNSCC patients, whereas "coping by suppression" and "coping by social support" were most utilized among MS patients. Emotional-focused coping was most prevalent among HNSCC patients and lowest among the MS patients. Level of avoidance coping was similar between the groups. The coping of the general HNSCC patients differed most from the MS patients. An association was shown between increased coping efforts and lowered mood. In particular, avoidance coping was associated with lowered mood. These associations were stronger among the MS patients than HNSCC patients. Drinking to cope was most prevalent among the laryngectomized group, and was correlated with BDI scores in all groups. Furthermore, adequate coping seems to be to limit avoidance coping and promote coping by acceptance. The response pattern of the COPE inventory seems to be valid among HNSCC and MS patients.
- [Show abstract] [Hide abstract] ABSTRACT: To examine how coping styles among patients with multiple sclerosis (MS) change over time and how patients' coping styles after 5 years are associated with disability pension. Seventy-six MS patients and 94 healthy controls were included in this study. The patients were examined at baseline and 5 years later. This included a neurological examination and information on disability pension and a questionnaire assessing coping (the COPE scale). Controls were registered at baseline only. Compared to healthy controls, MS patients were more passive in coping with disease related distress. This was even more pronounced 5 years later. Disability pensioned patients employed more social support, venting of emotions and behavioural disengagement at follow-up. This study shows that patients with MS employ coping styles that may be inadequate and this is not improved by adaption over time. Although patients also use strategies to enhance their lives, these findings suggest that there may be a potential for improving the lives of patients with MS through interventions that may enhance adequate coping with the disease.
- [Show abstract] [Hide abstract] ABSTRACT: To identify independent risk factors of mortality in a community-based Parkinson disease (PD) cohort during prospective long-term follow-up. A community-based prevalent sample of 230 patients with PD from southwestern Norway was followed prospectively with repetitive assessments of motor and nonmotor symptoms from 1993 to 2005. Information on vital status until October 20, 2009, was obtained from the National Population Register in Norway. Cox proportional hazards models were applied to identify independent predictors of mortality during follow-up. Chronological age, Unified Parkinson's Disease Rating Scale (UPDRS) motor score, levodopa equivalent dose, probable REM sleep behavior disorder, psychotic symptoms, dementia, and use of antipsychotics were included as time-dependent variables, and age at onset (AAO) and sex as time-independent variables. Of 230 patients, 211 (92%) died during the study period. Median survival time from motor onset was 15.8 years (range 2.2-36.6). Independent predictors of mortality during follow-up were AAO (hazard ratio [HR] 1.40 for 10-years increase, p = 0.029), chronological age (HR 1.51 for 10-years increase, p = 0.043), male sex (HR 1.63, p = 0.001), UPDRS motor score (HR 1.18 for 10-point increase, p < 0.001), psychotic symptoms (HR 1.45, p = 0.039), and dementia (HR 1.89, p = 0.001). This population-based long-term study demonstrates that in addition to AAO, chronological age, motor severity, and dementia, psychotic symptoms independently predict increased mortality in PD. In contrast, no significant impact of antipsychotic or antiparkinsonian drugs on survival was observed in our PD cohort. Early prevention of motor progression and development of psychosis and dementia may be the most promising strategies to increase life expectancy in PD.
Stavanger University Hospital
Stavenger, Rogaland, Norway
- Department of Neurology
Haukeland University HospitalBergen, Hordaland, Norway
Umeå, Västerbotten, Sweden
- Department of Psychology
Central Peninsula HospitalSXQ, Alaska, United States