Mild Cognitive Impairment as a risk factor for Parkinson's disease dementia

Background The International Parkinson and Movement Disorders Society criteria for mild cognitive impairment in Parkinson’s disease were recently formulated. Objectives The aim of this international study was to evaluate the predictive validity of the comprehensive (level II) version of these criteria by assessment of their contribution to the hazard of Parkinson’s disease dementia. Methods Individual patient data were selected from four separate studies on cognition in Parkinson’s disease that provided information on demographics, motor examination, depression, neuropsychological examination suitable for application of level II criteria, and longitudinal follow-up for conversion to dementia. Survival analysis evaluated the predictive value of level II criteria for cognitive decline towards dementia as expressed by the relative hazard of dementia. Results A total of 467 patients were included. The analyses showed a clear contribution of impairment according to level II mild cognitive impairment criteria, age and severity of Parkinson’s disease motor symptoms to the hazard of dementia. There was a trend of increasing hazard of dementia with declining neuropsychological performance. Conclusions This is the first large international study evaluating the predictive validity of level II mild cognitive impairment criteria for Parkinson’s disease. The results showed a clear and unique contribution of classification according to level II criteria to the hazard of Parkinson’s disease dementia. This finding supports their predictive validity and shows that they contribute important new information on the hazard of dementia, beyond known demographic and Parkinson’s disease specific factors of influence.Michael J. Fox Foundation Dutch Parkinson Foundatio

A Scoping Review of Home Produced Heroin and Amphetamine Type Stimulant Substitutes: Implications for Prevention, Treatment and Policy

Several home-produced substances such as krokodil and boltushka are prevalent in many Eastern European countries. Anecdotal reports of its use have been circulating in Germany and Norway; however, this has not been confirmed. Its use has also been reported by the media in the USA, although only one confirmed report of its use exists. Home-produced drugs are associated with high levels of morbidity and a number of complex health issues such as the spread of blood borne viruses, gangrene, and internal organ damage. The high incidence of HIV rates amongst people who inject home-produced substances is a public health concern. The resulting physical health consequences of injecting these crude substances are very severe in comparison to heroin or amphetamine acquired in black markets. Due to this fact and the increased mortality associated with these substances, professionals in the area of prevention, treatment, and policy development need to be cognisant of the presentation, harms, and the dangers associated with home-produced substances globally. This scoping review aimed to examine existing literature on the subject of home-produced heroin and amphetamine-type stimulant substitutes. The review discussed the many implications such research may have in the areas of policy and practice. Data were gathered through the use of qualitative secondary resources such as journal articles, reports, reviews, case studies, and media reports. The home production of these substances relies on the utilisation of precursor drugs such as less potent stimulants, tranquillizers, analgesics, and sedatives or natural plant ingredients. The Internet underpins the facilitation of this practice as recipes, and diverted pharmaceutical sales are available widely online, and currently, ease of access to the Internet is evident worldwide. This review highlights the necessity of prevention, education, and also harm reduction related to home-produced drugs and also recommends consistent monitoring of online drug fora, online drug marketplaces, and unregulated pharmacies

A Two-Stage Meta-Analysis Identifies Several New Loci for Parkinson's Disease

A previous genome-wide association (GWA) meta-analysis of 12,386 PD cases and 21,026 controls conducted by the International Parkinson's Disease Genomics Consortium (IPDGC) discovered or confirmed 11 Parkinson's disease (PD) loci. This first analysis of the two-stage IPDGC study focused on the set of loci that passed genome-wide significance in the first stage GWA scan. However, the second stage genotyping array, the ImmunoChip, included a larger set of 1,920 SNPs selected on the basis of the GWA analysis. Here, we analyzed this set of 1,920 SNPs, and we identified five additional PD risk loci (combined p<5x10(-10), PARK16/1q32, STX1B/16p11, FGF20/8p22, STBD1/4q21, and GPNMB/7p15). Two of these five loci have been suggested by previous association studies (PARK16/1q32, FGF20/8p22), and this study provides further support for these findings. Using a dataset of post-mortem brain samples assayed for gene expression (n = 399) and methylation (n = 292), we identified methylation and expression changes associated with PD risk variants in PARK16/1q32, GPNMB/7p15, and STX1B/16p11 loci, hence suggesting potential molecular mechanisms and candidate genes at these risk loci

Unilateral pallidotomy in PD - A controlled study of cognitive and behavioral effects

Objective: To investigate whether unilateral pallidotomy affects cognitive and behavioral functioning. Methods: At baseline and after 6 months we assessed neuropsychological functioning in 35 patients with advanced PD. After baseline examination, patients were randomized to pallidotomy within 1 month (6 left-sided, 13 right-sided) or to pallidotomy after follow-up assessment 6 months later (n = 16; control group). We performed neuropsychological tests of language, visuospatial function, memory, attention, and executive functions. Self ratings and proxy ratings of memory problems and dysexecutive symptoms were also collected. Results: No significant differences over time were found between pallidotomy and control groups, with the exception of a decrease of verbal fluency in the left-sided pallidotomy group. Conclusions: Unilateral pallidotomy is relatively safe with respect to cognition and behavior. Left-sided pallidotomy may lead to minor deterioration in verbal fluency. The sample size of this study is too small, however, to rule out the possibility of infrequent but clinically important side effects.</p

Unilateral pallidotomy in PD - A controlled study of cognitive and behavioral effects

Objective: To investigate whether unilateral pallidotomy affects cognitive and behavioral functioning. Methods: At baseline and after 6 months we assessed neuropsychological functioning in 35 patients with advanced PD. After baseline examination, patients were randomized to pallidotomy within 1 month (6 left-sided, 13 right-sided) or to pallidotomy after follow-up assessment 6 months later (n = 16; control group). We performed neuropsychological tests of language, visuospatial function, memory, attention, and executive functions. Self ratings and proxy ratings of memory problems and dysexecutive symptoms were also collected. Results: No significant differences over time were found between pallidotomy and control groups, with the exception of a decrease of verbal fluency in the left-sided pallidotomy group. Conclusions: Unilateral pallidotomy is relatively safe with respect to cognition and behavior. Left-sided pallidotomy may lead to minor deterioration in verbal fluency. The sample size of this study is too small, however, to rule out the possibility of infrequent but clinically important side effects

Unilateral pallidotomy in Parkinson's disease: a randomised, single-blind, multicentre trial

Background The results of several cohort studies suggest that patients with advanced Parkinson's disease would benefit from unilateral pallidotomy. We have assessed the efficacy of unilateral pallidotomy in a randomised, single-blind, multicentre trial. Methods We enrolled 37 patients with advanced Parkinson's disease who had, despite optimum pharmacological treatment, at least one of the following symptoms: severe response fluctuations, dyskinesias, painful dystonias, or bradykinesia, Patients were randomly assigned to unilateral pallidotomy within 1 month or to pallidotomy after the primary outcome assessment (6 months later). The primary outcome was the difference between the groups in median changes on the motor examination section of the unified Parkinson's disease rating scale (UPDRS 3) score done in the off phase. Secondary outcome measures included levodopa-induced dyskinesias (dyskinesia rating scale [DRS]) and extent of disability (UPDRS 2). Findings The median UPDRS 3 off score of the pallidotomy patients improved from 47 to 32.5, whereas that of control patients slightly worsened from 52.5 to 56.5 (p <0.001). In the on phase the median DRS score improved 50% in pallidotomy patients compared with no change in controls. The UPDRS 2 off score improved with a median of 7 in the pallidotomy group. Two treated patients had major adverse effects. Interpretation Unilateral pallidotomy is an effective treatment in patients with advanced Parkinson's disease, who have an unsatisfactory response to pharmacological treatment