12, –, 15 Briefly, a study neurologist performed general medical and neurologic examinations and semi-structured interviews at baseline to obtain medical, drug, and family history (defined as the report of a first- or second-degree relative with PD). The clinical assessments have been described in detail and the same procedures were followed in each cohort. The remaining 440 patients were eligible for this study and the 7-year clinical visits were complete. Furthermore, 57 declined genotyping, 31 have no available DNA sample or DNA was not extractable, and 7 did not consent to follow-up. Since enrollment, 70 had a diagnosis other than PD during follow-up.
The patients are under continued follow-up, and only those with a confirmed clinical or pathologic (if performed postmortem) diagnosis of PD according to the UK Brain Bank criteria at their latest or final clinical visit were included.
The consent rate to participation among incident patents was 80% in the ParkWest study, 94% in the PINE study, and 94% in the NYPUM study. 12, –, 15 A total of 212 patients were enrolled in the ParkWest study, 211 in the PINE study, and 182 in the NYPUM study. The participants in this study take part in the Norwegian ParkWest study, the Swedish NYPUM study, and the Scottish PINE study, 3 prospective population-based longitudinal incidence studies of PD (recruitment running between 20) with similar study design.
By determining the role of GBA variants in the evolution of motor and functional decline, we provide important new insights into the distinct clinical profile of GBA-associated PD, with importance for both more individualized patient care and more efficient clinical trial design. In this study, we address this using longitudinal data from 3 deeply phenotyped population-based studies of incident PD in Northern Europe to comprehensively survey the progression of motor impairment in early PD. PD is primarily a movement disorder yet few studies have analyzed the effect of GBA carrier status on motor decline in early PD. 6, –, 8 Further, GBA mutation status is an independent risk factor for cognitive impairment. 1, –, 5 GBA-associated PD has been shown to manifest at a younger age and with a lower median survival time from diagnosis compared to idiopathic PD. Mutations and polymorphisms in GBA are estimated to be found in up to 12% of patients with PD of European descent, and mutations in 15%–20% of Ashkenazi Jewish cases, making GBA the most significant genetic risk factor for PD. The glucocerebrosidase gene ( GBA) encodes the lysosomal enzyme β-glucocerebrosidase. The disease course is typically progressive and in the advanced stages, motor impairment results in significant disability. Parkinson disease (PD) is a neurodegenerative disorder defined by the presence of motor symptoms and signs, though nonmotor symptoms are common in all stages of the disease. Glossary ADL = activities of daily living CI = confidence interval GBA = glucocerebrosidase gene H&Y = Hoehn & Yahr LED = levodopa-equivalent dose MMSE = Mini-Mental State Examination PD = Parkinson disease PPMI = Parkinson's Progression Markers Initiative UPDRS = Unified Parkinson’s Disease Rating Scale