Study design

The Norwegian ParkWest study is a prospective longitudinal cohort study of patients with incident Parkinson’s Disease from Western and Southern Norway. The study area comprises the four counties of Sogn and Fjordane, Hordaland, Rogaland and Aust-Agder, with a total population of more than 1 million inhabitants. The study was approved by the Regional Committee for Medical Research Ethics, University of Bergen. All personnel who were part of the study group received comprehensive training in diagnostic and evaluation procedures before the start of the study and thereafter twice yearly.

ParkWest map

 

 

 

 

Case ascertainment

Patients

We sought to recruit all residents in the study area with incident PD identified during a 22 month period between November 1st 2004 and 31st of August 2006. All five neurology units within the study area participated.

Patients with suspected incident PD and related parkinsonian disorders in Norway are supposed to be referred to neurologists early after disease onset, according to the Norwegian Medicines Agency’s regulations and guidelines, to initiate antiparkinsonian medication. In a recent nationwide survey, 95.0% of Norwegian patients with PD reported that their disease was managed by a neurologist.

Nevertheless, in an attempt to achieve total ascertainment of patients with incident PD the following search strategies were applied:

  • hand searching of all referral letters to the participating study centres for symptoms possibly representing incident parkinsonism
  • notification of all other hospital departments and all general practitioners, including consulting physicians of nursing homes, geriatric care centres and other institutions for persons of older age, by regular mail before the start of the study and by email reminders twice during the screening period
  • cooperation with the only neurologist exclusively working outside the five hospitals within the study area
  • electronic screening of hospital databases for patients being diagnosed with PD for the first time during the screening period and for 3 months after to capture delays in coding, and
  • an electronic population screening of 43 716 individuals of all ages, including institutionalized persons, within the largest participating county 6 months after the end of the screening period by linkage to general practitioners’ electronic medical record systems. Electronic screening comprised search for written terms including each of the four cardinal motor features of the disease, “Parkinson” and “ParkWest”, as well as the International Classification of Diseases system, 10th revision (ICD-10) diagnostic codes for PD (G20), secondary parkinsonism (G21), other degenerative diseases of the basal ganglia (G23), other extrapyramidal and movement disorders (G25) and the International Classification of Primary Care, second edition, electronic version (ICPC-2e) codes for abnormal involuntary movements (N08) and parkinsonism (N87).
  • In addition, general practitioner files and drug prescriptions were searched electronically for antiparkinsonian drugs, including trade names of levodopa, various dopamine agonists, COMT inhibitors and selegiline. Single and combined search terms and diagnostic codes were used. Records dating back to 1 year before the start of the study were considered for screening.

 

Diagnostic and evaluation procedures

A multiple step diagnostic procedure was applied to identify patients with suspected incident PD. As experience from previous comprehensive epidemiological studies in the area suggested excellent compliance of general practitioners and other involved sources, we did not perform a run-in period prior to the formal recruitment period.

 

Screening procedures and initial study diagnosis (step 1)

The screening visit comprised assessment of the patient’s disease history, significant comorbidity, drug history, current medication and a general neurological examination by a study neurologist in all subjects, and the Mini-Mental State Examination when cognitive impairment was suspected. All subjects who consented to long term study participation and met the broad provisional criteria for incident PD, defined as the unequivocal presence of at least two of the four cardinal motor signs, typical disease history with evidence of progressive parkinsonism, no dementia at the onset of parkinsonism and no severe atypical signs (severe postural instability or frequent falls; prominent autonomic, pyramidal, cerebellar features or eye movement disorders), were directly forwarded to more comprehensive baseline assessments (step 2, see below).

In cases in which a diagnosis of PD was difficult to determine at the screening visit because of multiple potential underlying causes (“uncertain PD”), reassessments were conducted before study entry. In addition, [123I]FP-CIT dopamine transporter imaging was available to aid in the differential diagnosis.

Patients with an initial study diagnosis of PD refusing full study participation were offered routine neurological follow-up by a study neurologist.

No attempt was made to systematically follow subjects who presented features definitely excluding PD, such as pre-existing dementia, or those who were free from parkinsonism. However, these and all other subjects with non-PD parkinsonism in need of a diagnostic work-up or neurological care were offered to be followed at the participating departments. In addition, general practitioners were asked to re-refer subjects if they developed a clinical picture suspicious of PD.

 

Baseline assessments (step 2)

Baseline investigations were conducted during two consecutive days in the presence of a caregiver, including semi-structured interviews on medical and drug history, and family history of neurological and psychiatric diseases, as well as a general neurological and medical examination.

The severity of parkinsonism and disability was assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS), including the modified Hoehn and Yahr staging and the Schwab and England scale.

Cognitive functioning was assessed using the Mini-Mental State Examination and an extensive neuropsychological test battery, and the Informant Questionnaire for Cognitive Decline in the Elderly, validated for the diagnosis of dementia, was completed by the caregiver.

Patients and relatives were asked if dementia had developed before, simultaneously with or within 12 months of onset of motor symptoms.

Cerebral MRI scans with volume uptake were performed in close temporal relation to the baseline examinations.

 

Follow-up (step 3)

Patients who consented to study participation were undergoing prospective follow-up, including clinical evaluation by a study neurologist at least twice yearly. Biannual assessments comprised semi-structured interviews and standardized rating scales, including the UPDRS to evaluate changes in drug therapy, subjective and objective response to dopaminergic treatment, and development of features atypical of PD.

 

Final study diagnosis (step 4)

At a mean time of 28 months from the screening visit, all patients originally evaluated for the study were provided with a final study diagnosis of PD according to widely acknowledged criteria under the supervision of two neurologists specializing in movement disorders, taking into consideration all available patient material through to the latest study visit, including medical history, clinical and radiological examination, drug response in those on dopaminergic treatment and dopamine transporter imaging when available (n = 31).

Patients who developed dementia before or within 1 year of motor onset were excluded.

When not meeting the diagnostic criteria for PD, subjects were provided with a diagnosis of other parkinsonian syndromes, based on (i) the revised consensus criteria for the diagnosis of dementia with Lewy bodies (DLB), (ii) the consensus statement on the diagnosis of multiple system atrophy, (iii) National Institute of Neurological Disorders and the Society for Progressive Supranuclear Palsy clinical research criteria, (iv) a history of repeated stroke and/or (related) stepwise progression of parkinsonism and compatible neuroradiological findings regarding a diagnosis of “vascular parkinsonism” and (v) development of parkinsonism, preferably symmetric, in temporal relation to exposure to neuroleptics or other drugs with antagonistic properties to dopamine receptors for a diagnosis of “drug induced parkinsonism”.

Diagnostic and Statistical Manual of Mental disorders, fourth edition (DSM-IV-TR) criteria were used to provide a diagnosis of Alzheimer’s disease. A diagnosis of monosymptomatic resting tremor was based on the Consensus Statement of the Movement Disorder Society on Tremor.

Essential tremor was diagnosed when patients presented with predominant postural tremor of moderate amplitude, located in the upper limbs or head, with no signs of parkinsonism and not caused by medication, alcohol or hyperthyroidism.

Det er stengt for kommentarer.