Parkinson's disease-cognitive rating scale: Psychometrics for mild cognitive impairment

Mov Disord. 2013 Jul 19. doi: 10.1002/mds.25568. [Epub ahead of print]

Fernández de Bobadilla R, Pagonabarraga J, Martínez-Horta S, Pascual-Sedano B, Campolongo A, Kulisevsky J.

Source

Movement Disorders Unit, Neurology Department, Sant Pau Hospital, Barcelona, Spain; Movement Disorders Section, Biomedical Research Institute (IIB-Sant Pau), Barcelona, Spain; Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.

Abstract

Lack of validated data on cutoff scores for mild cognitive impairment (MCI) and sensitivity to change in predementia stages of Parkinson's disease (PD) limit the utility of instruments measuring global cognition as screening and outcome measures in therapeutic trials. Investigators who were blinded to PD-Cognitive Rating Scale (PD-CRS) scores classified a cohort of prospectively recruited, nondemented patients into a PD with normal cognition (PD-NC) group and a PD with MCI (PD-MCI) group using Clinical Dementia Rating (CDR) and the Mattis Dementia Rating Scale-2 (MDRS-2). The discriminative power of the PD-CRS for PD-MCI was examined in a representative sample of 234 patients (145 in the PD-NC group; 89 in the PD-MCI group) and in a control group of 98 healthy individuals. Sensitivity to change in the PD-CRS score (the minimal clinically important difference was examined with the Clinical Global Impression of Change scale and was calculated with a combination of distribution-based and anchor-based approaches) was explored in a 6-month observational multicenter trial involving a subset of 120 patients (PD-NC, 63; PD-MCI, 57). Regression analysis demonstrated that PD-CRS total scores (P < 0.001) and age (P = 0.01) independently differentiated PD-NC from PD-MCI. Area under the receiver operating characteristic curve (AUC) analysis (AUC, 0.85; 95% confidence interval, 0.80-0.90) indicated that a score ≤81 of 134 was the optimal cutoff point on the total score for the PD-CRS (sensitivity, 79%; specificity, 80%; positive predictive value, 59%; negative predictive value, 91%). A range of change from 10 to 13 points on the PD-CRS total score was indicative of clinically significant change. These findings suggest that the PD-CRS is a useful tool to identify PD-MCI and to track cognitive changes in nondemented patients with PD.

Mild cognitive impairment in Parkinson's disease.

Age Ageing. 2013 Jul 17. [Epub ahead of print]

Yarnall AJ, Rochester L, Burn DJ.

Source

Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, Tyne and Wear NE4 5PL, UK.

Abstract

The concept of mild cognitive impairment (MCI) in the general population has received increased attention over recent years, and is associated with risk of progression to Alzheimer's disease. Within Parkinson's disease (PD), MCI (PD-MCI) is also now recognised to be relatively common, with certain subtypes predicting progression to Parkinson's disease dementia (PDD). Recently, criteria to better characterise PD-MCI and its subtypes have been produced by the Movement Disorder Society. In contrast to the population as a whole, where amnestic MCI is the most common subtype, non-amnestic PD-MCI dominates, with prominent executive and attention dysfunction. Although the pathophysiology of PD-MCI is poorly understood and encompasses both PD and non-PD pathology, it is most likely the result of a complex interaction between neurotransmitter dysfunction, synaptic pathology, protein aggregation and neuronal damage. Determining the factors that influence the progression of these pathologies in PD and the individuals at risk of ultimately developing PDD is critical for targeted intervention and drug discovery studies. Further work is required, however, to determine the significance of PD-MCI and also to validate the diagnostic criteria. This would be best delivered in the form of longitudinal studies in homogenous cohorts of PD participants, to allow prognostication and generalisation among the PD population. At the present time, no drug therapies are available for PD-MCI. Management includes screening for the disorder, excluding treatable causes of cognitive decline and cautious use of dopamine agonists and medications such as anticholinergics.

Acute complications of movement disorders surgery: Effects of age and comorbidities

Mov Disord. 2013 Jul 16. doi: 10.1002/mds.25610. [Epub ahead of print]

Rughani AI, Hodaie M, Lozano AM.

Source

Neuroscience Institute, Maine Medical Center, Portland, Maine, United States.

Abstract

The most common indication for movement disorder surgery is Parkinson's disease (PD), and the incidence of PD increases with age. The analysis reported here was undertaken with the primary goal of examining whether there is a relationship between peri-operative complications and age. The Nationwide Inpatient Sample (Agency for Healthcare Research and Quality, Rockville, MD, USA) was queried for 10 years beginning in 1999 for patients undergoing deep brain stimulator insertion, pallidotomy, and thalamotomy for treatment of PD, essential tremor, and dystonia. Inpatient complications, including death, stroke (both ischemic and hemorrhagic), and other overall complications were examined. The relative risks associated with advanced age; primary diagnosis; treatment modality; the diagnoses of hypertension, diabetes, and nicotinism; and the cumulative number of comorbidities were examined. There were 5464 patients who met inclusion criteria, including 4145 patients treated for PD and 4961 patients treated with deep brain stimulation (DBS). Overall in-hospital mortality was 0.26%, with 0.15% related to surgical factors. There was a correlation between in-hospital mortality, increasing age, and number of medical comorbidities. After multivariate regression no factor remained predictive of mortality. Having more than 1 medical comorbidity or PD increased the risk of in-hospital complications. Patients with PD were more likely to suffer hemorrhage or stroke. Hypertension, diabetes, nicotinism, and modality of treatment were not associated with increased mortality, hemorrhage or stroke risk, or in-hospital mortality in univariate or multivariate analysis. Both age and medical comorbidity are correlated with in-hospital complications, but age appears to serve as a surrogate for comorbidity. Surgery for PD appears to carry an increased risk of hemorrhage or stroke and in-hospital complications.

Measurement of costs and scales for outcome evaluation in health economic studies of Parkinson's disease

Mov Disord. 2013 Jul 16. doi: 10.1002/mds.25571. [Epub ahead of print]

Dodel R, Jönsson B, Reese JP, Winter Y, Martinez-Martin P, Holloway R, Sampaio C, Růžička E, Hawthorne G, Oertel W, Poewe W, Stebbins G, Rascol O, Goetz CG, Schrag A.

Source

Department of Neurology, Philipps-University Marburg, Marburg, Germany.

Abstract

Health economic studies in Parkinson's disease (PD) have become increasingly common in recent years. Because several methodologies and instruments have been used to assess cost and outcomes in PD, the Movement Disorder Society (MDS) commissioned a Task Force to assess their properties and make recommendations regarding their use. A systematic literature review was conducted to explore the use of those instruments in PD and to determine which should be selected for this review. We assessed approaches to evaluate cost of illness (COI), cost effectiveness, and cost utilities, which include the use of direct (standard gamble, time trade-off. and visual analogue scales) and indirect instruments to measure health status and utilities. No validated instruments/models were identified for the evaluation of COI or cost-effectiveness in patients with PD; therefore, no instruments in this group are recommended. Among utility instruments, only a few of these outcome instruments have been used in the PD population, and only limited psychometric data are available for these instruments with respect to PD. Because psychometric data for further utility instruments in conditions other than PD already exist, the standard gamble and time trade-off methods and the EQ-5D (a European quality-of-life health states instrument) and Health Utility Index instruments met the criteria for scales that are "recommended (with limitations)," but only the EQ-5D has been assessed in detail in PD patients. The MDS Task Force recommends further study of these instruments in the PD population to establish core psychometric properties. For the assessment of COI, the Task Force considers the development of a COI instrument specifically for PD, like that available for Alzheimer's disease.

Rasagiline adjunct therapy in patients with Parkinson's disease: Post hoc analyses of the PRESTO and LARGO trials

Parkinsonism Relat Disord. 2013 Jul 9. pii: S1353-8020(13)00219-8. doi: 10.1016/j.parkreldis.2013.06.001. [Epub ahead of print]

Elmer LW.

Source

Department of Neurology, University of Toledo College of Medicine, Toledo, OH 43614, USA.

Abstract

BACKGROUND:

Rasagiline was safe and effective when used as adjunct therapy with levodopa in patients with moderate-to-advanced Parkinson's disease (PD) in the phase III PRESTO and LARGO studies.

OBJECTIVE:

To assess clinical effects of rasagiline 1 mg/day on cardinal PD symptoms and motor fluctuations in defined patient subgroups using pooled data from PRESTO and LARGO.

METHODS:

Both double-blind, randomized, and placebo-controlled studies included PD patients with motor fluctuations despite optimized therapy with levodopa, with or without concomitant dopamine agonists (DA) or catechol-O-methyltransferase inhibitor (COMT-I) treatment. These post hoc analyses measured effects of rasagiline 1 mg vs placebo on individual cardinal PD symptoms during ON time and mean change from baseline in daily OFF time in subgroups of patients who at baseline were receiving only levodopa, were considered "mild fluctuators" (daily OFF time ≤ 4 h), and who were or were not receiving concomitant DA or COMT-I therapy.

RESULTS:

Compared with placebo, rasagiline significantly improved all cardinal PD symptoms and significantly reduced adjusted mean daily OFF time when used as first adjunct therapy in levodopa-treated patients and in patients with mild motor fluctuations. Significant improvement in motor fluctuations was reported with rasagiline regardless of concomitant DA or COMT-I use. Overall incidence of dopaminergic adverse events did not increase with concomitant DA or COMT-I use.

CONCLUSION:

Rasagiline was an effective first adjunct therapy in levodopa-treated patients; benefited patients with signs of early "wearing off"; improved all cardinal PD symptoms; and further improved symptoms in patients already receiving other adjunctive dopaminergic treatment.

Advances in the genetics of Parkinson disease

Nat Rev Neurol. 2013 Jul 16. doi: 10.1038/nrneurol.2013.132. [Epub ahead of print]

Trinh J, Farrer M.

Source

Department of Medical Genetics, UBC Pavillion Hospital, 2nd floor, Room S-132 Koerner Building, VCHRI, 2211 Wesbrook Mall, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada.

Abstract

Parkinson disease (PD) is a multifactorial neurodegenerative disease that was long considered the result of environmental factors. In the past 15 years, however, a genetic aetiology for PD has begun to emerge. Here, we review results from linkage and next-generation sequencing studies of familial parkinsonism, as well as candidate gene and genome-wide association findings in sporadic PD. In these studies, many of the genetic findings overlap, despite different designs and study populations, highlighting novel therapeutic targets. The molecular results delineate a sequence of pathological events whereby deficits in synaptic exocytosis and endocytosis, endosomal trafficking, lysosome-mediated autophagy and mitochondrial maintenance increase susceptibility to PD. These discoveries provide the rationale, molecular insight and research tools to develop neuroprotective and disease-modifying therapies.

A Single-Center, Cross-Sectional Prevalence Study of Impulse Control Disorders in Parkinson Disease: Association With Dopaminergic Drugs

J Clin Psychopharmacol. 2013 Jul 12. [Epub ahead of print]

Poletti M, Logi C, Lucetti C, Del Dotto P, Baldacci F, Vergallo A, Ulivi M, Del Sarto S, Rossi G, Ceravolo R, Bonuccelli U.

Source

From the *Department of Neuroscience, University of Pisa, Pisa; †Neurology Unit, Hospital of Viareggio, USL 12 Toscana; and ‡Unit of Epidemiology and Biostatistics, Institute of Clinical Physiology, National Research Council, Pisa, Italy.

Abstract

The current study aimed at establishing the prevalence of impulse control disorders (ICDs) in patients with Parkinson disease (PD) and their association with demographic, drug-related, and disease-related characteristics. We performed a single-center cross-sectional study of 805 PD patients. Impulse control disorders were investigated with the Questionnaire for Impulsive Compulsive Disorders in Parkinson's Disease; also comorbid neuropsychiatric complications (dementia, delusions, visual hallucinations) were investigated with clinical interviews and ad hoc instruments (Parkinson Psychosis Questionnaire and Neuropsychiatry Inventory). Impulse control disorders were identified in 65 patients (prevalence, 8.1%), with pathological gambling and hypersexuality the most frequent. Impulse control disorders were present in 57 of 593 cognitively preserved patients (prevalence, 9.6%) and in 8 of 212 demented patients (prevalence, 3.8%). Impulse control disorders were significantly associated with dopamine agonists (odds ratio [OR], 5.50; 95% confidence interval [CI], 2.60-12.46; P < 0.0001) and levodopa (OR, 2.43; 95% CI, 1.06-6.35; P = 0.034). Impulse control disorders frequency was similar for pramipexole and ropinirole (16.6% vs 12.5%; OR, 1.45; 95% CI, 0.79-2.74; P = 0.227). Additional variables associated with ICDs were male sex and younger age. These findings suggested that dopaminergic treatments in PD are associated with increased odds of having an ICD, but also other demographic and clinical variables are associated with ICDs, suggesting the multifactorial nature of the ICD phenomenon in PD.

C9ORF72 Intermediate Repeat Copies Are a Significant Risk Factor for Parkinson Disease

Ann Hum Genet. 2013 Jul 12. doi: 10.1111/ahg.12033. [Epub ahead of print]

Nuytemans K, Bademci G, Kohli MM, Beecham GW, Wang L, Young JI, Nahab F, Martin ER, Gilbert JR, Benatar M, Haines JL, Scott WK, Züchner S, Pericak-Vance MA, Vance JM.

Source

University of Miami, Miller School of Medicine, John P. Hussman Institute for Human Genomics, Biomedical Research building, 1501 NW 10th Ave, Miami, FL, 33136, USA.

Abstract

We set out to determine whether expansions in the C9ORF72 repeat found in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) families are associated with Parkinson disease (PD). We determined the repeat size in a total of 889 clinically ascertained patients (including PD and essential tremor plus Parkinsonism (ETP)) and 1144 controls using a repeat-primed PCR assay. We found that large C9ORF72 repeat expansions (>30 repeats) were not contributing to PD risk. However, PD and ETP cases had a significant increase in intermediate (>20 to 30+) repeat copies compared to controls. Overall, 14 cases (13 PD, 1 ETP) and three controls had >20 repeat copies (Fisher's exact test p = 0.002). Further, seven cases and no controls had >23 repeat copies (p = 0.003). Our results suggest that intermediate copy numbers of the C9ORF72 repeat contribute to risk for PD and ETP. This also suggests that PD, ALS and FTD share some pathophysiological mechanisms of disease. Further studies are needed to elucidate the contribution of the C9ORF72 repeat in the overall PD population and to determine whether other common genetic risk factors exist between these neurodegenerative disorders.

Imaging of Dopamine in PD and Implications for Motor and Neuropsychiatric Manifestations of PD

Front Neurol. 2013 Jul 9;4:90. Print 2013.

de la Fuente-Fernández R.

Source

Section of Neurology, Hospital A. Marcide, Complejo Hospitalario Universitario de Ferrol (CHUF) , Ferrol , Spain.

Abstract

Parkinson's disease (PD) is characterized by dopamine depletion in the putamen, which leads to motor dysfunction. As the disease progresses, a substantial degree of dopamine depletion also occurs in caudate and nucleus accumbens. This may explain a number of neuropsychiatric manifestations, including depression, apathy, and cognitive decline. Dopamine replacement therapy partially restores motor function but long-term treatment is often associated with motor complications (motor fluctuations and dyskinesias). Positron emission tomography (PET) studies suggest that the dopamine release rate is substantially higher in PD subjects with motor complications compared to stable responders. Notably, this differential pattern of dopamine release is already present in the early stages of the disease, before motor complications become clinically apparent. Converging evidence suggests that striatal dopamine depletion in PD leads to reduced plasticity in the primary motor cortex and, presumably, in non-motor cortical areas as well. Although dopamine replacement therapy tends to restore physiological plasticity, treatment-induced motor, and neuropsychiatric complications could be related to abnormalities in corticostriatal synaptic plasticity.

Alcohol Consumption, Types of Alcohol, and Parkinson's Disease

PLoS One. 2013 Jun 19;8(6):e66452. Print 2013.

Liu R, Guo X, Park Y, Wang J, Huang X, Hollenbeck A, Blair A, Chen H.

Source

Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America.

Abstract

BACKGROUND:

The epidemiologic evidence on alcohol consumption and Parkinson's disease (PD) is equivocal. We prospectively examined total alcohol consumption and consumption of specific types of alcoholic beverage in relation to future risk of PD.

METHODS:

The study comprised 306,895 participants (180,235 male and 126,660 female) ages 50-71 years in 1995-1996 from the NIH-AARP Diet and Health Study. Consumption of alcoholic beverages in the past 12 months was assessed in 1995-1996. Multivariate odds ratios (OR) and 95% confidence intervals (CI) were obtained from logistic regression models.

RESULTS:

A total of 1,113 PD cases diagnosed between 2000 and 2006 were included in the analysis. Total alcohol consumption was not associated with PD. However, the association differed by types of alcoholic beverages. Compared with non-beer drinkers, the multivariate ORs for beer drinkers were 0.79 (95% CI: 0.68, 0.92) for <1 drink/day, 0.73 (95% CI: 0.50, 1.07) for 1-1.99 drinks/day, and 0.86 (95% CI: 0.60, 1.21) for ≥2 drinks/day. For liquor consumption, a monotonic increase in PD risk was suggested: ORs (95% CI) were 1.06 (0.91, 1.23), 1.22 (0.94, 1.58), and 1.35 (1.02, 1.80) for <1, 1-1.99, and ≥2 drinks/day, respectively (P for trend <0.03). Additional analyses among exclusive drinkers of one specific type of alcoholic beverage supported the robustness of these findings. The results for wine consumption were less clear, although a borderline lower PD risk was observed when comparing wine drinkers of 1-1.99 drinks/day with none drinkers (OR = 0.74, 95% CI: 0.53, 1.02).

CONCLUSIONS:

OUR RESULTS SUGGEST THAT BEER AND LIQUOR CONSUMPTION MAY HAVE OPPOSITE ASSOCIATIONS WITH PD: low to moderate beer consumption with lower PD risk and greater liquor consumption with higher risk. These findings and potential underlying mechanisms warrant further investigations.

Repetitive transcranial magnetic stimulation improves handwriting in Parkinson's disease

Parkinsons Dis. 2013;2013:751925. doi: 10.1155/2013/751925. Epub 2013 May 8.

Randhawa BK, Farley BG, Boyd LA.

Source

Graduate Program in Rehabilitation Sciences, University of British Columbia, 212-2177 Wesbrook Mall, Vancouver, BC, Canada V6T 1Z3.

Abstract

Background. Parkinson disease (PD) is characterized by hypometric movements resulting from loss of dopaminergic neurons in the substantia nigra. PD leads to decreased activation of the supplementary motor area (SMA); the net result of these changes is a poverty of movement. The present study determined the impact of 5 Hz repetitive transcranial magnetic stimulation (rTMS) over the SMA on a fine motor movement, handwriting (writing cursive "l"s), and on cortical excitability, in individuals with PD. Methods. In a cross-over design, ten individuals with PD were randomized to receive either 5 Hz or control stimulation over the SMA. Immediately following brain stimulation right handed writing was assessed. Results. 5 Hz stimulation increased vertical size of handwriting and diminished axial pressure. In addition, 5 Hz rTMS significantly decreased the threshold for excitability in the primary motor cortex. Conclusions. These data suggest that in the short term 5 Hz rTMS benefits functional fine motor task performance, perhaps by altering cortical excitability across a network of brain regions. Further, these data may provide the foundation for a larger investigation of the effects of noninvasive brain stimulation over the SMA in individuals with PD.