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.

The prognosis of stroke survivors primarily discharged to their homes.

OBJECTIVES: Stroke is one of the leading causes for nursing home placement (NHP). We have studied the prognosis and risk factors regarding NHP for stroke patients initially discharged to their homes. MATERIALS AND METHODS: All stroke patients in the municipality of Stavanger, Norway, between January 1, 1996, and March 31, 2004, were included and followed until death or May 31, 2012. Time intervals for NHP and death were compared to an age- and sex-matched, stroke-free control cohort. Logistic regression analysis was used to assess risk factors for NHP. RESULTS: A total of 452 patients were included. A total of 48 patients (10.6%) were directly placed in a nursing home, while 401 patients (88.7%) were discharged to their homes; 180 patients (44.7%) directly and 221 patients (55.3%) after temporary rehabilitation. Of the patients discharged to their homes, 29.7% needed NHP at a later time point as compared to 19.9% of the controls (P<.001). Logistic regression analysis showed that only age (P<.001) was a risk factor for NHP. Stroke patients discharged home and stroke patients admitted directly to nursing home were significantly younger at time of NHP; stroke patients discharged home died significantly earlier than the controls. CONCLUSIONS: Almost 90% of the stroke patients could be discharged to their homes, but they needed more often NHP in the long run than the stroke-free controls. Stroke patients discharged to their homes were younger at the time of NHP and death indicating that the stroke deficit may contribute to increased morbidity and mortality in this patient group.

The long-term development of non-motor problems after STN-DBS.

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 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Motor symptoms after deep brain stimulation of the subthalamic nucleus.

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 METHODS: 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 the same symptoms in a non-operated, historical reference population. RESULTS: During 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.

Progression and survival in Parkinson's disease with subthalamic nucleus stimulation.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: This study gives no support to a postulated disease modifying or neuroprotective effect of STN-DBS in patients with PD.

Health related quality of life in patients recently diagnosed with multiple sclerosis.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Frequencies of falls and associated features at different stages of Parkinson's disease.

BACKGROUND AND PURPOSE: To examine the frequencies and clinical characteristics of fallers and non-fallers at different stages of Parkinson's disease (PD). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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

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.

Autonomic symptoms and dopaminergic treatment in de novo Parkinson's disease.

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. METHODS: A 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). RESULTS: In 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.

Subjective sleep problems in patients with early Parkinson's disease.

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

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.

Choice of psychological coping in laryngectomized, head and neck squamous cell carcinoma patients versus multiple sclerosis patients.

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.

Differential effect of environmental risk factors on postural instability gait difficulties and tremor dominant Parkinson's disease.

Both environmental and genetic factors contribute to the development of Parkinson's disease (PD). We have examined environmental risk factors in a Norwegian population of incident PD patients and controls, the Norwegian ParkWest study. All five neurological wards in the study area of Western Norway participated in the study. A 4-step diagnostic procedure was used to establish a representative cohort of patients with incident PD at a high level of diagnostic accuracy. 212 incident PD patients and 175 age- and gender-matched controls were included. PD patients and controls were asked for information on occupation, education, exposure to pesticides, tobacco, alcohol, and caffeine. Agricultural work was associated with a higher risk of PD (OR 1.75 (1.03-3.0) P = 0.009). There were no differences as to other occupations. Smoking (OR 0.63 (0.42-0.95) P = 0.016) and alcohol use (OR 0.55 P = 0.008) were associated with a lower risk for PD. Interestingly, this inverse association was only seen in postural instability gait difficulties (PIGD) PD (P = 0.046 for smoking, P = 0.07 for alcohol consumption), and not in tremor dominant (TD) PD which was similar to controls. Consumption of coffee was lower in PD patients (3.3 ± 1.8 cups per day vs. 3.8 ± 2.0 in controls P = 0.02). In the regression model including intake of alcohol, coffee, and smoke, only coffee (P = 0.007) and alcohol intake (P = 0.021) remained significant whereas smoking was no longer significant. Thus, it seems as though only coffee intake reduces the risk of PD in general while associations to alcohol and smoking differ between PIGD and TD-PD patients.

Parkinson's disease and hospital admissions: frequencies, diagnoses and costs.

OBJECTIVE: To evaluate the frequencies, causes and costs related to hospital admissions for patients with Parkinson's disease (PD) and controls. METHODS: In a prospective cohort study, 108 patients with PD from a population-based prevalence study and 854 age- and sex-matched controls were followed regarding admissions to the Stavanger University Hospital over a period of 12 years. RESULTS: There was no significant difference regarding the number of patients admitted, number of admissions or length of stay between the two cohorts. Based on 2005 prices, the costs per person year of survival were EUR 3288 for patients with PD and EUR 2466 for control individual with incremental costs of EUR 822. However, the difference in costs was not statistically significant. The two cohorts had a different distribution of diagnoses causing hospital admissions. Patients with PD were more often admitted for PD-related symptoms and falls, while vascular disorders and cancer were substantially more common in control individuals. CONCLUSION: Hospitalization in PD does not induce incremental costs. The diagnoses causing hospital admissions were different in patients with PD as compared with controls. Our results indicate that cancer and vascular diseases might be less common in patients with PD than in the general population.

Caregiver distress associated with neuropsychiatric problems in patients with early Parkinson's disease: the Norwegian ParkWest study.

OBJECTIVES: We investigated caregiver distress associated with neuropsychiatric problems in patients with newly diagnosed Parkinson's disease (PD). MATERIALS AND METHODS: Persons who were next of kins of 198 patients and 168 healthy individuals completed the Neuropsychiatric Inventory Caregiver Distress Scale. RESULTS: Even at the time of diagnosis PD has a considerable impact on the next of kins' experience of distress. Nearly 50% reported distress, significantly more than in the control group, and more than one-quarter reported moderate severe distress. Except the more rarely reported neuropsychiatric symptoms, apathy was the symptom that most frequently caused caregiver distress in PD patient's next of kin (94.5%), followed by depression (88.2%), anxiety (86.2%) and irritability (83.3%). CONCLUSIONS: The study underlines the importance of focusing on neuropsychiatric aspects in patients and associated caregiver distress even in early PD management.

The effect of statin therapy on the progression of carotid artery stenosis in relation to stenosis severity.

OBJECTIVES: To examine the effect of early statin treatment on progression of arteriosclerosis in internal carotid arteries (ICA); to compare the progression of arteriosclerosis in ICA of patients treated with a statin to the progression seen in drug-naïve patients. PATIENTS AND METHODS: We performed repetitive Doppler scans of 363 carotid arteries with ICA stenosis > or =40% in 254 patients over time. Information on statin therapy and other risk factors for stroke were correlated with the annual change in degree of ICA stenosis. RESULTS: In statin-treated patients, 19% of ICA stenosis showed a progression while 74% showed a regression of stenosis. In statin-naïve patients, 63% of stenotic arteries showed a progression, while a reduction could be observed in 28%. Decrease of ICA stenosis was most accentuated in patients with a mild stenosis and was independent of serum cholesterol levels. CONCLUSION: Treatment with statins already in early stages of ICA stenosis might delay the progression and even reverse the degree of stenosis.

The role of APOE alleles in incident Parkinson's disease. The Norwegian ParkWest Study.

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.

Coping with multiple sclerosis: a 5-year follow-up study.

OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Occurrence and risk factors for apathy in Parkinson disease: a 4-year prospective longitudinal study.

BACKGROUND: Apathy is a common but under-recognised behavioural disorder associated with depression and cognitive impairment in patients with Parkinson disease (PD). However, the longitudinal course of apathy in PD has not been studied. OBJECTIVE: To examine the occurrence of and risk factors for apathy over time in a representative sample of patients with PD. METHODS: A sample of 139 patients was drawn from a population-based prevalence study of PD in Rogaland County, Western Norway. Apathy was measured with the Neuropsychiatric Inventory, using a composite score >or=4 to indicate clinically significant apathy. Additional measurements included standardised rating scales for parkinsonism, depression and cognitive impairment. A follow-up evaluation was carried out in 79 patients (78.2% of the survivors) 4 years later. RESULTS: Of the 79 patients included in this study, 29 patients (36.7%) had never had apathy, 11 (13.9%) had persistent apathy, and a further 39 (49.4%) developed apathy during follow-up. At follow-up, patients with apathy were more frequently depressed and demented than never-apathetic patients. Dementia at baseline and a more rapid decline in speech and axial impairment during follow-up were independent risk factors for incident apathy. CONCLUSIONS: Apathy is a persistent behavioural feature in PD with a high incidence and prevalence over time. Progression of motor signs predominantly mediated by non-dopaminergic systems may be a useful preclinical marker for incident apathy in PD.

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.