Monoamine oxidase B inhibitors versus other dopaminergic agents in early Parkinson's disease.

BACKGROUND: It has been postulated that monoamine oxidase B (MAO-B) inhibitors alter disease progression in Parkinson's disease (PD) but trials have produced conflicting results. OBJECTIVES: To assess the effectiveness and safety of long-term use of MAO-B inhibitors compared with other dopaminergic agents in early PD. SEARCH STRATEGY: We searched several electronic databases including: the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2009), MEDLINE (January 1950 to February 2009) and EMBASE (January 1980 to February 2009). We also handsearched neurology and movement disorders conference proceedings, checked reference lists of relevant studies and contacted other researchers. SELECTION CRITERIA: We included all randomised controlled trials that compared a MAO-B inhibitor with other dopaminergic agents (presently levodopa or dopamine agonists) in patients with early PD, where treatment and follow up lasted at least one year. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion, assessed the methodological quality, and extracted the data. Additional data were provided by the original authors. Random-effects models were used to analyse results, where appropriate. MAIN RESULTS: Only two eligible trials were included (593 patients), both of reasonable quality although one was unblinded. Both trials compared selegiline with a dopamine agonist, whilst one also compared selegiline with levodopa. MAO-B inhibitors were not associated with a significant increase or decrease in deaths compared with levodopa (odds ratio (OR) 0.96; 95% confidence interval (CI) 0.52 to 1.76) or dopamine agonists (OR 1.30; 95% CI 0.69 to 2.45). Those receiving MAO-B inhibitors were more likely to require add-on therapy during follow-up than those receiving levodopa (OR 12.02; 95% CI 6.78 to 21.31) or dopamine agonist (OR 2.00; 95% CI 1.05 to 3.81). There was a reduction in motor fluctuations with MAO-B inhibitors compared with levodopa (OR 0.55; 95% CI 0.32 to 0.94) but not dopamine agonists (OR 1.15; 95% CI 0.65 to 2.05). Withdrawals due to adverse events were less common with MAO-B inhibitors than with dopamine agonists (OR 0.11; 95% CI 0.01 to 0.99). AUTHORS' CONCLUSIONS: MAO-B inhibitors are one option for the early treatment of PD although they have weaker symptomatic effects than levodopa and dopamine agonists. They may reduce the rate of motor fluctuations compared with initial levodopa therapy and may have fewer significant adverse effects than the older agonists but data are too few to provide reliable conclusions.

Shape analysis of 123I-N-omega-fluoropropyl-2-beta-carbomethoxy-3beta-(4-iodophenyl) nortropane single-photon emission computed tomography images in the assessment of patients with parkinsonian syndromes.

PURPOSE: The purpose of this study was to show the viability and performance of a shape-based pattern recognition technique applied to I-N-omega-fluoropropyl-2-beta-carbomethoxy-3beta-(4-iodophenyl) nortropane single-photon emission computed tomography (FP-CIT SPECT) in patients with parkinsonism. METHODS: A fully automated pattern recognition tool, based on the shape of FP-CIT SPECT images, was written using Java. Its performance was evaluated and compared with QuantiSPECT, a region-of-interest-based quantitation tool, and observer performance using receiver operating characteristic analysis and kappa statistics. The techniques were compared using a sample of patients and controls recruited from a prospective community-based study of first presentation of parkinsonian symptoms with longitudinal follow up (median 3 years). RESULTS: The shape-based technique as well as the conventional semiquantitative approach was performed by experienced observers. The technique had a high level of automation, thereby avoiding observer/operator variability. CONCLUSION: A pattern recognition approach is a viable alternative to traditional methods of analysis in FP-CIT SPECT and has additional advantages.

Age-related selection bias in Parkinson's disease research: are we recruiting the right participants?

OBJECTIVE: To describe, and explore heterogeneity in, age at onset/diagnosis in Parkinson's disease (PD) and compare mean age at onset/diagnosis in incidence studies with that in general PD research studies. METHODS: We systematically reviewed studies of PD incidence. We meta-analysed mean age at onset/diagnosis and age-stratum-specific incidence rates. We compared age-specific incidence rates in screening studies in the elderly with whole-population studies. We collated mean ages at onset/diagnosis in clinical studies of PD in five journals July-December 2016. RESULTS: In 17 studies reporting sufficient data to pool, mean age at onset/diagnosis was 69.6 years (95% CI 68.2-71.1), but heterogeneity was high (I2 = 96%). In ten of these studies reporting age at diagnosis specifically, the pooled mean age at diagnosis was slightly higher (71.6 [95% CI 70.6-72.6]) with lower, but still high, heterogeneity (I2 = 84%). In twelve whole-population studies reporting age-specific incidence rates, these peaked in age 70-79 (pooled incidence rate per 100,000 = 93.8 [95% CI 80.3-107.4]). Heterogeneity increased with each increase in age stratum (0% in youngest to 88% in oldest age stratum). Pooled age-specific incidence rates in five population-based screening studies of older age groups were several-fold higher than in whole-population studies. The mean of the reported mean ages at onset/diagnosis in recently published research studies was 60.8 (SD 5.6). CONCLUSION: The mean age of onset/diagnosis PD is about 70, although this may be an underestimate due to under-diagnosis in the elderly. Many published studies use age-unrepresentative subjects: the effect of this selection bias deserves further study.

Comprehensive Geriatric Assessment for Prevention of Delirium After Hip Fracture: A Systematic Review of Randomized Controlled Trials.

OBJECTIVES: To assess the efficacy of comprehensive geriatric assessment (CGA) in prevention of delirium after hip fracture. DESIGN: Systematic review and metaanalysis. SETTING: Ward based models on geriatrics wards and visiting team based models on orthopaedics wards were included. PARTICIPANTS: Four trials (three European, one U.S.; 973 participants) were identified. Two assessed ward-based, and two assessed team-based interventions. MEASUREMENTS: MEDLINE, EMBASE, CINAHL and PsycINFO databases; Clinicaltrials.gov; and the Central Register of Controlled Trials were searched. Reference lists from full-text articles were reviewed. Incidence of delirium was the primary outcome. Length of stay, delirium severity, institutionalization, long-term cognition and mortality were predefined secondary outcomes. Duration of delirium was included as a post hoc outcome. RESULTS: There was a significant reduction in delirium overall (relative risk (RR) = 0.81, 95% confidence interval (CI) = 0.69-0.94) in the intervention group. Post hoc subgroup analysis found this effect to be preserved in the team-based intervention group (RR = 0.77, 95% CI = 0.61-0.98) but not the ward-based group. No significant effect was observed on any secondary outcome. CONCLUSION: There was a reduction in the incidence of delirium after hip fracture with CGA. This is in keeping with results of non-randomized controlled trials and trials in other populations. Team-based interventions appeared superior in contrast to the Ellis CGA paper, but it is likely that heterogeneity in interventions and population studied affected this.

Age-, and gender-specific incidence of vascular parkinsonism, progressive supranuclear palsy, and parkinsonian-type multiple system atrophy in North East Scotland: the PINE study.

INTRODUCTION: There have been few incidence studies of vascular parkinsonism (VP), progressive supranuclear palsy (PSP), and parkinsonian-type multiple system atrophy (MSA-P). We measured the age-, gender- and socioeconomic-specific incidence rates for these conditions in north-east Scotland. METHODS: Incident non drug-induced parkinsonian patients were identified prospectively over three years by several overlapping methods from a baseline primary care population of 311,357. Parkinsonism was diagnosed if patients had two or more cardinal motor signs. Patients had yearly follow-up to improve diagnostic accuracy. Incidence rates using the diagnosis by established research criteria at latest follow-up were calculated for each condition by age, gender, and socioeconomic status. RESULTS: Of 377 patients identified at baseline with possible or probable parkinsonism, 363 were confirmed as incident patients after median follow-up of 26 months (mean age 74.8 years, SD 9.8; 61% men). The crude annual incidence was 3.2 per 100,000 (95% confidence interval (CI) 2.2-4.3) for VP, 1.7 per 100,000 (95% CI 1.0-2.4) for PSP, and 1.4 per 100,000 (95% CI 0.8-2.1) for MSA-P. VP and MSA-P were more common in men (age-adjusted male to female ratios 2.58 (95% CI 1.65-3.83) and 8.65 (95% CI 4.73-14.5) respectively). Incidence did not vary with socioeconomic status. DISCUSSION: This is the first community-based, prospective study to report the incidence of vascular parkinsonism and the third to report the incidence of PSP and MSA-P. Further follow-up and comparison with similar studies in different populations will yield valuable prognostic and aetiological information on these conditions.

Age-, gender-, and socioeconomic status-specific incidence of Parkinson's disease and parkinsonism in northeast Scotland: the PINE study.

There have been few high quality incidence studies of Parkinson's disease (PD). We measured age-, gender- and socioeconomic-specific incidence rates for parkinsonism and PD in north-east Scotland, and compared our results with those of previous high quality studies. Incident patients were identified prospectively over three years by several overlapping methods from primary care practices (total population 311,357). Parkinsonism was diagnosed if patients had two or more cardinal motor signs. Drug-induced parkinsonism was excluded. Patients had yearly follow-up to improve diagnostic accuracy. Incidence rates using clinical diagnosis at latest follow-up were calculated for all parkinsonism and for PD by age, gender and socioeconomic status. Meta-analysis with similar studies was performed. Of 377 patients identified at baseline with possible or probable parkinsonism, 363 were confirmed as incident patients after median follow-up of 26 months (mean age 74.8 years, SD 9.8; 61% men). The crude annual incidence of parkinsonism was 28.7 per 100,000 (95% confidence interval (CI) 25.7-31.8) and PD 17.9 per 100,000 (95% CI 15.5-20.4). PD was more common in men (age-adjusted male to female ratio 1.87:1, 95% CI 1.55-2.23) but there was no difference by socioeconomic status. Meta-analysis of 12 studies showed an incidence of PD (adjusted to the 1990 Scottish population) of 14.6 per 100,000 (95% CI 12.2-17.3) with considerable heterogeneity (I(2) 95%), partially explained by population size and recruitment duration. The incidence of PD was similar to other high quality studies. The incidence of PD was not affected by socioeconomic status.

The mini-mental Parkinson's (MMP) as a cognitive screening tool in people with Parkinson's disease.

BACKGROUND: Cognitive decline is common in Parkinson's disease (PD) but may not be adequately identified by the mini-mental state examination (MMSE), which is better suited to Alzheimer's disease. The mini-mental Parkinson (MMP) examination is a cognitive screening tool designed in French specifically for PD. We aimed to establish the validity and reliability of the English language version of the MMP compared with the MMSE. METHODS: People with various stages of PD underwent testing with the MMP and MMSE, which was then compared with a reference standard battery of neuropsychological tests to identify those with significant cognitive impairment. RESULTS: Forty-nine patients were recruited. Both the MMP and MMSE were significantly correlated with scores on all the neuropsychological tests in the validation battery. The median MMP score was proportionally lower (80% of maximum) than the MMSE (90% of maximum) in PD patients with cognitive impairment and those with prior neuropsychiatric complications but there was no difference between the MMP and MMSE in areas under the curves (0.84) for detecting cognitive impairment. Test-retest reliability of the MMP was good (intra-class correlation coefficient 0.793). An MMP of 28 or lower out of 32 detected cognitive impairment with 87% sensitivity and 76% specificity. DISCUSSION: The English language version of the MMP has now been validated. It detects more cognitive deficits in PD patients than the MMSE and identifies significant cognitive impairment in those with PD at least as well as the MMSE.

Parkinson's disease misdiagnosed as stroke.

Parkinson's disease (PD) is a neurodegenerative disease, the clinical features of which are usually asymmetrical at presentation. This can lead to difficulty in differentiating it from other asymmetric neurological disorders. We present two cases where idiopathic PD was initially misdiagnosed as stroke, leading to a delay in appropriate symptomatic therapy. Physicians involved in diagnosis and treatment of people with strokes should consider PD when formulating their differential diagnosis.