Progression of fatigue in Parkinson's disease - a 9-year follow-up.

BACKGROUND AND PURPOSE: Although highly disabling, the pathogenesis and evolution of fatigue in Parkinson's disease (PD) is largely unknown, and no sufficiently documented treatment currently exists. The aim of the present study was to investigate the evolution of fatigue during the first 9 years after diagnosis. METHODS: This study is part of the Norwegian ParkWest collaboration, a prospective population-based longitudinal cohort study. The present study comprised 191 newly diagnosed patients and 170 control participants. Fatigue was assessed by the Fatigue Severity Scale, with examinations at baseline and then every other year up to 9 years of follow-up. Linear mixed models were applied to investigate possible variables associated with fatigue. RESULTS: It was found that there was a statistically significant increase in the proportion of PD patients with fatigue during the first 9 years after diagnosis. A large proportion of patients had a significant increase or decrease in fatigue score between consecutive visits. In addition, the relative risk of persistent fatigue and ever having fatigue was higher than for controls. There were statistically significant longitudinal associations between higher levels of fatigue and female gender, comorbidity at baseline, depressive symptoms, dependency in activities of daily living and better cognitive functioning. Lower levels of fatigue were associated with the use of dopamine agonists. CONCLUSION: Fatigue is a common, severely limiting symptom in PD. This study demonstrates associations with other factors that could yield a better understanding of the symptom and thus possible treatment strategies, although further investigations are necessary to establish causal relationships.

Inflammation and fatigue in early, untreated Parkinson's Disease.

OBJECTIVES: Parkinson's disease (PD)-related fatigue is a significant clinical problem, and the pathological processes that cause fatigue remain unknown. The aim of the present study was to explore the possible association of peripheral inflammation markers and fatigue in PD. MATERIALS & METHODS: We included 47 drug naïve, newly diagnosed PD patients with low (≤3.0) or high (>5.5) fatigue levels as evaluated by the Fatigue Severity Scale (FSS). Strict diagnostic criteria were applied for inclusion. Patients with possible confounding causes for fatigue were excluded. Serum concentrations of a panel of inflammatory markers (IL-8, TNF-α, MCP1, MIP-1ß, IL-6, IL-6R, p-selectin, E-selectin-1, ICAM, VCAM-1, CCL5, IL1-Ra, and TNFR1) were measured using ELISA technology in PD patients with and without fatigue to assess the potential relationships of fatigue in newly diagnosed, treatment-naïve patients. RESULTS: Fatigued PD patients had significantly higher levels of the IL-1 receptor antagonist (IL1-Ra) (1790 pg/mL (SD1007) vs 1262 pg/mL (SD379)) and of the adhesion molecule VCAM 1 (1071 ng/mL (SD276) vs 895 ng/mL (SD229)) than non-fatigued patients. A binary logistic regression model, including high or low FSS score as the dependent variable and UPDRS motor score, MADRS, MMSE, ESS, and IL1-Ra/VCAM-1 as independent variables, showed a significant effect both for IL1-Ra and VCAM-1. CONCLUSIONS: Higher serum levels of the inflammatory molecules IL1-Ra and VCAM-1 were associated with higher fatigue levels in patients with newly diagnosed, drug-naïve PD. These findings highlight an altered immune response as a potential contributor to PD-related fatigue, from the earliest clinical stages of the disease.

Fatigue in early Parkinson's disease: the Norwegian ParkWest study.

BACKGROUND AND PURPOSE: Fatigue is a common and disabling non-motor symptom in Parkinson's disease (PD). The pathogenesis is unknown, and the treatment options are limited. The aim of the present study was to investigate the development of fatigue during the first year after diagnosis. METHODS: The study design was a prospective, controlled population-based longitudinal cohort study, comprising 181 de novo, drug-naïve patients with PD and 162 control participants. PD was diagnosed according to the Gelb criteria. Fatigue was assessed by the Fatigue Severity Scale (FSS). Both groups were assessed for fatigue at baseline and after 1 year. RESULTS: Patients reported more fatigue than the control subjects at baseline and at the 1-year follow-up evaluation. The FSS scores in the patient group improved from a mean score of 4.4 (SD 1.6) to 4.0 (SD 1.6). Patients with fatigue at baseline received higher doses of dopaminergic medication during follow-up. Patients who received dopamine agonists improved slightly more than patients who received levodopa. A regression analysis did not show a correlation between an improvement in fatigue and a change in disease severity, depressive symptoms, sleep problems, apathy or cognitive impairment. CONCLUSION: Fatigue is a common symptom in PD, also in early, untreated patients. During the first year of observation, an improvement in the fatigue scores was found. The improvement could not be attributed to a change in disease severity or depressive symptoms. The results indicate a better effect of dopamine agonists than of levodopa. This may have implications for treatment in patients with PD-associated fatigue.

Risk factors for a non-favorable outcome after treated European neuroborreliosis.

AIM: To identify possible risk factors for reduced health-related quality of life (HRQoL) and fatigue after treated Lyme neuroborreliosis (LNB). METHODS: We included 50 patients with LNB and analyzed associations between their demographic, clinical, and laboratory characteristics at baseline and outcome at 30 months assessed by the self-report questionnaires Short Form-36 (SF-36) and Fatigue Severity Scale (FSS). RESULTS: Lower scores in the SF-36 domain Physical Component Summary were associated with pretreatment symptom duration >6 weeks (B = -11.0, P = 0.001) and non-complete recovery at 4 months (B = -5.5, P = 0.037) (R(2) = 0.35). Lower scores in the SF-36 domain Mental Component Summary were associated with non-complete recovery at 4 months (B = -8.9, P = 0.01 (R(2) = 0.14). Higher FSS scores were associated with pretreatment symptom duration >6 weeks (B = 1.4, P = 0.006), high scores on the composite clinical score pretreatment (B = 0.1, P = 0.003), and non-complete recovery at 4 months (B = 1.6, P = 0.005) (R(2) = 0.46). No laboratory test results were associated with these predefined outcomes. CONCLUSIONS: Delayed treatment start, more symptoms and findings before treatment, and non-complete recovery at 4 months after treatment are possible predictors of a poorer HRQoL and more fatigue 30 months after treated LNB. We did not find age, gender, educational level, involvement of the central nervous system, coexisting diseases, or cerebrospinal fluid findings to be associated with reduced HRQoL or fatigue. Our findings should be replicated in future studies before any conclusions can be drawn.

Fatigue in early Parkinson's disease. Minor inconvenience or major distress?

BACKGROUND AND PURPOSE: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

European neuroborreliosis: neuropsychological findings 30 months post-treatment.

BACKGROUND: The aim of this study was to compare neuropsychological (NP) functioning in patients with Lyme neuroborreliosis (LNB) 30months after treatment to matched controls. METHODS: We tested 50 patients with LNB and 50 controls with the trail-making test (TMT), Stroop test, digit symbol test, and California Verbal Learning test (CVLT). A global NP sumscore was calculated to express the number of low scores on 23 NP subtasks. RESULTS: Mean scores were lower amongst LNB-treated patients than amongst controls on tasks assessing attention/executive functions: (Stroop test 4: 77.6 vs. 67.0, P=0.015), response/processing speed (TMT 5: 23.4 vs. 19.2, P=0.004), visual memory (digit symbol recall: 6.6 vs. 7.2, P=0.038), and verbal memory (CVLT list B: 4.68 vs. 5.50, P=0.003). The proportion of patients and controls with NP sumscores within one SD from the mean in the control group (defined as normal) and between one and two SD (defined as deficit) were similar, but more LNB-treated patients than controls had a sumscore more than two SD from the mean (defined as impairment) (8 vs. 1, P=0.014). CONCLUSIONS: As a group, LNB-treated patients scored lower on four NP subtasks assessing processing speed, visual and verbal memory, and executive/attention functions, as compared to matched controls. The distribution of NP dysfunctions indicates that most LNB-treated patients perform comparable to controls, whilst a small subgroup have a debilitating long-term course with cognitive problems.

European neuroborreliosis: quality of life 30 months after treatment.

OBJECTIVES: The prognosis after Lyme neuroborreliosis (LNB) is debated. The aim of this study was to assess health-related Quality of Life (QoL) and neurological symptoms 30 months after treatment in European patients with LNB. MATERIALS AND METHODS: In a prospective case-control designed study, we investigated 50 well-characterized patients with LNB who had participated in a treatment trial for LNB 30 months earlier and 50 matched control persons with the health QoL questionnaire Short-Form 36 (SF-36), the Fatigue Severity Scale (FSS), the Montgomery and Åsberg Depression Rating Scale (MADRS), the Starkstein Apathy Scale (SAS), and the Mini Mental State (MMS). Clinical and demographic data were collected by semi-structured interviews and clinical neurological examination. RESULTS: Lyme neuroborreliosis-treated patients scored lower than control persons in the SF-36 domains physical component summary (PCS) (44 vs 51 P < 0.001) and mental component summary (MCS) (49 vs 54 P = 0.010). They also scored lower than control persons in all the SF-36 subscales, except for bodily pain, and on FSS (3.5 vs 2.1 P < 0.001), but not on MMS (28 vs 29 P = 0.106). There was a difference in MADRS (3.1 vs 0. 8 P = 0.003) and SAS (13 vs 11 P = 0.016), but the scores were low in both groups. Fatigue was the most frequently reported symptom among LNB-treated patients (50%). Patients who reported complete recovery (56%) after LNB had similar QoL scores as the controls. CONCLUSION: European persons treated for LNB have poorer health-related QoL and have more fatigue than persons without LNB.

Incidence of Parkinson's disease in Norway: the Norwegian ParkWest study.

OBJECTIVE: To present the incidence of Parkinson's disease (PD) in Norway and to explore gender influences on incidence and age at onset, as well as severity and pattern of parkinsonism at the time of diagnosis in a representative drug naïve cohort with newly diagnosed PD. METHODS: In four Norwegian counties comprising a base population of 1 052 075 inhabitants, multiple sources of case ascertainment and a four step diagnostic procedure were used to establish a representative cohort of patients with incident PD at a high level of diagnostic accuracy. Of a total of 604 subjects referred to the study, 265 individuals fulfilled the clinical research criteria of PD at their latest clinical visit, at a mean 28 months after identification. RESULTS: The incidence of PD in the study area, age standardised to the 1991 European standard population, was 12.6/10(5yr-1) (95% CI 11.1 to 14.2). The overall age standardised male to female ratio was 1.58 (95% CI 1.22 to 2.06), with a consistent male preponderance throughout all age groups. Clinical onset of PD was later in women than in men (68.6 vs 66.3 years; p = 0.062) whereas severity and pattern of parkinsonism in drug naïve patients was not different between genders at the time of diagnosis. CONCLUSION: Incidence rates of PD in Norway are similar to those in other Western European and American countries. Female gender was associated with a considerably lower risk of PD and slightly delayed motor onset but had no impact on severity of parkinsonism or clinical phenotype in incident drug naïve PD, suggesting that the female gender influences on the nigrostriatal system are most pronounced in the preclinical phase of the disease.

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.

Measuring fatigue in patients with Parkinson's disease - the Fatigue Severity Scale.

The objective was to compare the prevalence and severity of fatigue in patients with Parkinson's disease (PD) with that in two control groups, one consisting of randomly chosen control subjects of the same age and sex distribution and the other consisting of patients with coxarthrosis waiting to receive total hip replacement. We also explored the possible correlation of demographic and clinical data to the presence and severity of fatigue. Sixty-six patients with PD, 131 randomly chosen controls and 79 patients with coxarthrosis, waiting to receive total hip replacement, were evaluated for fatigue. Patients and controls with a depressive mood disorder or cognitive impairment had been excluded from the study. Fatigue was measured by the Fatigue Severity Scale (FSS). For the patients with PD the mean total FSS score was 4.1, compared with 2.7 amongst the randomly chosen control group and 2.9 in the group consisting of patients with coxarthrosis. Fifty per cent of the patients with PD had a mean total FSS score of 4 or higher, compared with 25% in both of the two control groups. There was no correlation between pain, presence of self-reported nocturnal sleep disorders or duration of PD and fatigue. The patients with fatigue did have a more advanced disease, measured both by Unified Parkinson's Disease Rating Scale score and Hoehn and Yahr stage. Although the univariate analyses indicated that more severe parkinsonism was correlated to the symptom, the multivariate analysis showed that none of the studied variables were significant explanatory factors for fatigue. Fatigue is a common symptom in patients with PD without depression or dementia. The study indicates that fatigue is an independent symptom of the disease without relation to other motor or non-motor symptoms.

Causes of death in a community-based study of Parkinson's disease.

INTRODUCTION: The aim of this community-based study of Parkinson's disease (PD) was to investigate the causes of death among PD patients over a 4-year period and to examine the quality of death certificates with regard to PD. PATIENTS AND METHODS: A total of 245 patients were diagnosed with PD on Jan 1st 1993 in a defined geographical area in Norway. This patient cohort was followed from 1993 until Dec 31st 1996. Some 84 patients died in the 4-year period of follow-up. Their death certificates were collected, and causes of death were registered. A control group with the same age and sex distribution as the decedents, from the same geographical area, were also examined for causes of death. RESULTS: We found that the deceased PD patients at baseline were older, had a higher Unified Parkinson's Disease Rating Scale (UPDRS) score and Hoehn and Yahr staging than those patients who did not die during the observation period. Twice as many PD patients (20%) as controls (9%) died from pneumonia, whereas more controls than patients died from ischemic heart disease. There was a trend towards more deaths from malignant neoplasms in the control group than among PD patients. Only 56% of the death certificates of the deceased patients had PD registered as either underlying or contributing cause of death. CONCLUSION: We found that in an unselected group of PD patients there is a significant increase in deaths from pneumonia. The low frequency of PD on deceased patients' death certificates show that research based on these certificates should be evaluated with caution.