Orthostatic Hypotension in Parkinson's Disease: The Relation of Blood Pressure Tests and Symptoms in Daily Life.

BACKGROUND: Orthostatic hypotension (OH) is common in Parkinson's disease (PD), but the relation between the results of orthostatic blood pressure tests and orthostatic symptoms in daily life is not clear. METHODS: We performed a cross-sectional study in an incident nontertiary care cohort of PD patients with additional recruitment of PD patients from our own outpatient clinic. We recruited sex- and age-matched controls. All participants underwent orthostatic blood pressure tests using continuous blood pressure measurements. Orthostatic symptoms experienced in daily life were assessed using autonomic symptom questionnaires (SCOPA-AUT and COMPASS-31). RESULTS: A total of 83 PD patients and 35 controls were included. Mean patient age was 69.2 years (standard deviation [SD]: 10.0). Mean disease duration was 6.6 years (SD, 0.8). The estimated prevalence of OH in PD was 24.1% (95% confidence interval: 16.2-34.3). There was no significant difference between PD patients with and without OH regarding reported daily orthostatic symptoms. Alternative OH criteria did not substantially improve this. CONCLUSIONS: Perceived orthostatic symptoms in daily life have no clear association with the results of a single orthostatic blood pressure test. Better diagnostic strategies are needed.

Development and external validation of a prognostic model in newly diagnosed Parkinson disease.

OBJECTIVE: To develop a prognostic model to predict disease outcomes in individual patients with Parkinson disease (PD) and perform an external validation study in an independent cohort. METHODS: Model development was done in the Comorbidity and Aging in Rehabilitation Patients: The Influence on Activities (CARPA) cohort (Netherlands). External validation was performed using the Cambridgeshire Parkinson's Incidence from GP to Neurologist (CamPaIGN) cohort (UK). Both are longitudinal incident cohort studies that prospectively followed up patients with PD from the time of diagnosis. A composite outcome measure was made in which patients were classified as having an unfavorable prognosis when they had postural instability or dementia at the 5-year assessment (or at the last assessment before loss to follow-up), or had died before this time. The final model was derived with a backward selection strategy from candidate predictor variables that were measured at baseline. RESULTS: In the resulting model, higher patient age, higher Unified Parkinson's Disease Rating Scale motor examination axial score, and a lower animal fluency score were all associated with a higher probability of an unfavorable outcome. External validation confirmed good discriminative ability between favorable and unfavorable outcomes with an area under the receiver operating characteristic curve of 0.85 (95% confidence interval 0.77-0.93) and a well-calibrated model with a calibration slope of 1.13 and no significant lack of fit (Hosmer-Lemeshow test: p = 0.39). CONCLUSION: We constructed a model that allows individual patient prognostication at 5 years from diagnosis, using a small set of predictor variables that can easily be obtained by clinicians or research nurses.

Cognitive change in newly-diagnosed patients with Parkinson's disease: a 5-year follow-up study.

Cognitive change is frequently observed in patients with Parkinson's disease (PD). However, the exact profile and extent of cognitive impairments remain unclear due to the clinical heterogeneity of PD and methodological issues in many previous studies. In this study, we aimed to examine the severity, frequency, and profile of cognitive changes in newly diagnosed PD patients over 5 years. At baseline and after 3 and 5 years, a hospital-based sample of PD patients (n = 59) and healthy controls (n = 40) were given neuropsychological tests covering six cognitive domains. Patients showed greater decline over time than healthy controls on all cognitive domains, except for attention. The profile of decline showed that psychomotor speed and memory were most affected. At the individual level 53% of the patients showed more cognitive decline than controls. Age at onset and memory impairment at baseline predicted cognitive decline. Cognitive functions in PD patients show greater decline in most domains than in healthy elderly over the course of 5 years. Due to selection bias as a result of attrition, the actual degree of decline may be greater than reported here.

Prognostic factors of motor impairment, disability, and quality of life in newly diagnosed PD.

OBJECTIVE: In Parkinson disease (PD), the rate of clinical progression is highly variable. To date, there are conflicting findings concerning the prognostic factors influencing the rate of progression. Methodologic issues such as the use of selected patients from therapeutic trials, and short durations of follow-up probably underlie this problem. We therefore designed a prospective follow-up study of a cohort of newly diagnosed patients with PD. METHODS: A cohort of 129 patients with newly diagnosed PD was assessed at baseline, and 1, 2, 3, and 5 years later. The rate of progression and its prognostic factors on the level of motor impairments, disability, and quality of life were investigated using linear mixed-model analysis. RESULTS: Annual increase of motor impairments measured with the Unified Parkinson's Disease Rating Scale-Motor Examination was estimated to be 2.46 points (95% confidence interval: 2.05-2.88). The main determinants of faster increase of motor impairments were male sex and cognitive dysfunction at the time of diagnosis. The main determinants of faster increase of disability were higher age at onset, cognitive dysfunction, and the presence of levodopa-nonresponsive motor symptoms at the time of diagnosis. No clinically relevant determinants were found for the decrease in quality of life. CONCLUSION: This study shows the importance of nondopaminergic symptoms at the time of diagnosis, because these symptoms are the main determinants of increased disability in the first 5 years of the disease.

Prevalence of orthostatic hypotension in Parkinson's disease: a systematic review and meta-analysis.

BACKGROUND: Although orthostatic hypotension (OH) is recognized as one of the main non-motor symptoms of Parkinson's disease (PD), there is inconsistent evidence about the prevalence of OH in PD. To estimate the prevalence of OH in PD more precisely we conducted a systematic review of the literature. METHODS: From PubMed and Embase searches with predefined inclusion criteria, we identified studies published up till December 2009. Prevalence numbers from studies were pooled using a non-linear random-effects meta-analysis. RESULTS: We found 25 studies from which the prevalence of OH could be calculated. The pooled estimate of the point prevalence of OH in PD was 30.1% (95% CI: 22.9% to 38.4%). We found a large statistical heterogeneity between studies which could not be reduced by several subgroup analyses. CONCLUSIONS: The estimated prevalence of OH in PD is 30%. However, due to the large heterogeneity between studies this pooled estimate should be interpreted with caution. More data from unselected population-based cohorts are needed.

Genome-wide association study confirms extant PD risk loci among the Dutch.

In view of the population-specific heterogeneity in reported genetic risk factors for Parkinson's disease (PD), we conducted a genome-wide association study (GWAS) in a large sample of PD cases and controls from the Netherlands. After quality control (QC), a total of 514,799 SNPs genotyped in 772 PD cases and 2024 controls were included in our analyses. Direct replication of SNPs within SNCA and BST1 confirmed these two genes to be associated with PD in the Netherlands (SNCA, rs2736990: P = 1.63 × 10(-5), OR = 1.325 and BST1, rs12502586: P = 1.63 × 10(-3), OR = 1.337). Within SNCA, two independent signals in two different linkage disequilibrium (LD) blocks in the 3' and 5' ends of the gene were detected. Besides, post-hoc analysis confirmed GAK/DGKQ, HLA and MAPT as PD risk loci among the Dutch (GAK/DGKQ, rs2242235: P = 1.22 × 10(-4), OR = 1.51; HLA, rs4248166: P = 4.39 × 10(-5), OR = 1.36; and MAPT, rs3785880: P = 1.9 × 10(-3), OR = 1.19).

Incidence and characteristics of chronic and lymphoplasmacytic sclerosing pancreatitis in patients scheduled to undergo a pancreatoduodenectomy.

BACKGROUND: The determination of the exact nature of a pancreatic head mass in a patient scheduled to undergo a pancreatoduodenectomy can be very difficult. This is important as patients who suffer from benign disease such as pancreatitis do not always require surgery. The aim of the present study was to analyse the incidence of pancreatitis and the signs and symptoms associated with these tumours mistaken for pancreatic cancer and the diagnostic procedures performed. METHODS: A consecutive group of patients who underwent a pancreatoduodenectomy between 1992 and 2005 with histopathologically proven pancreatic adenocarcinoma (PCA) and pancreatitis were analysed. RESULTS: The incidence of pancreatitis after pancreatoduodenectomy is 63 out of 639 patients who underwent a pancreaticoduodenectomy (9.9%). Of these patients, 24 patients (38%) had lymphoplasmacytic sclerosing pancreatitis (LPSP) and 31 patients (49%) had focal chronic pancreatitis. Eight patients (13%) had an intermediate form with characteristics of both. Pancreatic adenocarcinoma occurred in 227 patients (36%). The presence of pancreatitis without a discrete mass on endoscopic ultrasonography (EUS) seemed to have clinical relevance with a positive likelihood ratio of 5.1. Mortality after resection was nil in both groups. CONCLUSION: The incidence of pancreatitis is 9.9% for patients scheduled to undergo a pancreatoduodenectomy. Of these patients, 38% had LPSP, 13% had a intermediate form and 49% had focal chronic pancreatitis. The determination of the exact nature of a pancreatic head mass remains difficult.