The role of small intestinal bacterial overgrowth in Parkinson's disease

Mov Disord. 2013 May 27. doi: 10.1002/mds.25522. [Epub ahead of print]

Fasano A, Bove F, Gabrielli M, Petracca M, Assunta Zocco M, Ragazzoni E, Barbaro F, Piano C, Fortuna S, Tortora A, Di Giacopo R, Campanale M, Gigante G, Lauritano EC, Navarra P, Marconi S, Gasbarrini A, Bentivoglio AR.

Source

Department of Neurology, Catholic University of Sacred Heart, Gemelli University Hospital, Rome, Italy; Department of Neuroscience, AFaR-Fatebenefratelli Hospital, Rome, Italy.

Abstract

Parkinson's disease is associated with gastrointestinal motility abnormalities favoring the occurrence of local infections. The aim of this study was to investigate whether small intestinal bacterial overgrowth contributes to the pathophysiology of motor fluctuations. Thirty-three patients and 30 controls underwent glucose, lactulose, and urea breath tests to detect small intestinal bacterial overgrowth and Helicobacter pylori infection. Patients also underwent ultrasonography to evaluate gastric emptying. The clinical status and plasma concentration of levodopa were assessed after an acute drug challenge with a standard dose of levodopa, and motor complications were assessed by Unified Parkinson's Disease Rating Scale-IV and by 1-week diaries of motor conditions. Patients with small intestinal bacterial overgrowth were treated with rifaximin and were clinically and instrumentally reevaluated 1 and 6 months later. The prevalence of small intestinal bacterial overgrowth was significantly higher in patients than in controls (54.5% vs. 20.0%; P = .01), whereas the prevalence of Helicobacter pylori infection was not (33.3% vs. 26.7%). Compared with patients without any infection, the prevalence of unpredictable fluctuations was significantly higher in patients with both infections (8.3% vs. 87.5%; P = .008). Gastric half-emptying time was significantly longer in patients than in healthy controls but did not differ in patients based on their infective status. Compared with patients without isolated small intestinal bacterial overgrowth, patients with isolated small intestinal bacterial overgrowth had longer off time daily and more episodes of delayed-on and no-on. The eradication of small intestinal bacterial overgrowth resulted in improvement in motor fluctuations without affecting the pharmacokinetics of levodopa. The relapse rate of small intestinal bacterial overgrowth at 6 months was 43%. © 2013 Movement Disorder Society.

Exposure to pesticides or solvents and risk of Parkinson disease

Neurology. 2013 May 28;80(22):2035-41. doi: 10.1212/WNL.0b013e318294b3c8.

Pezzoli G, Cereda E.

Source

From the Parkinson Institute (G.P.), Istituti Clinici di Perfezionamento, Milan; and Fondazione IRCCS Policlinico San Matteo (E.C.), Pavia, Italy.

Abstract

OBJECTIVE:

To investigate the risk of Parkinson disease (PD) associated with exposure to pesticides and solvents using meta-analyses of data from cohort and case-control studies.

METHODS:

Prospective cohort and case-control studies providing risk and precision estimates relating PD to exposure to pesticides or solvents or to proxies of exposure were considered eligible. The heterogeneity in risk estimates associated with objective study quality was also investigated.

RESULTS:

A total of 104 studies/3,087 citations fulfilled inclusion criteria for meta-analysis. In prospective studies, study quality was not a source of heterogeneity. PD was associated with farming and the association with pesticides was highly significant in the studies in which PD diagnosis was self-reported. In case-control studies, study quality appeared to be a source of heterogeneity in risk estimates for some exposures. Higher study quality was frequently associated with a reduction in heterogeneity. In high-quality case-control studies, PD risk was increased by exposure to any-type pesticides, herbicides, and solvents. Exposure to paraquat or maneb/mancozeb was associated with about a 2-fold increase in risk. In high-quality case-control studies including an appreciable number of cases (>200), heterogeneity remained significantly high (>40%) only for insecticides, organochlorines, organophosphates, and farming; also, the risk associated with rural living was found to be significant.

CONCLUSIONS:

The literature supports the hypothesis that exposure to pesticides or solvents is a risk factor for PD. Further prospective and high-quality case-control studies are required to substantiate a cause-effect relationship. The studies should also focus on specific chemical agents.

Nicotine from edible Solanaceae and risk of Parkinson disease

Annals of Neurology 2013. ePub ahead of print.
Susan Searles Nielsen PhD,*, Gary M. Franklin MD, MPH, W. T. Longstreth Jr, MD, MPH, Phillip D. Swanson MD, PhD, Harvey Checkoway PhD

Objective
To test whether risk of Parkinson disease (PD) is associated with consumption of nicotine-containing edibles from the same botanical family as tobacco, Solanaceae, including peppers, tomatoes, and potatoes.

Methods
In a population-based study with 490 newly diagnosed idiopathic PD cases diagnosed during 1992–2008 at the University of Washington Neurology Clinic or Group Health Cooperative in western Washington State and 644 unrelated, neurologically normal controls, we examined whether PD was associated with self-reported typical frequency of consumption of peppers, tomatoes, tomato juice, and potatoes during adulthood, while adjusting for consumption of other vegetables, age, sex, race/ethnicity, tobacco use, and caffeine.

Results
PD was inversely associated with consumption of all edible Solanaceae combined (relative risk [RR] = 0.81, 95% confidence interval [CI] = 0.65–1.01 per time per day), but not consumption of all other vegetables combined (RR = 1.00, 95% CI = 0.92–1.10). The trend strengthened when we weighted edible Solanaceae by nicotine concentration (ptrend = 0.004). An inverse association was also evident for peppers specifically (ptrend = 0.005). The potentially protective effect of edible Solanaceae largely occurred in men and women who had never used tobacco or who had smoked cigarettes <10 years.

Interpretation
Dietary nicotine or other constituents of tobacco and peppers may reduce PD risk. However, confirmation and extension of these findings are needed to strengthen causal inferences that could suggest possible dietary or pharmaceutical interventions for PD prevention. Ann Neurol 2013

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A spotlight on current research - Nicotine from edible Solanaceae and risk of Parkinson disease' Annals of Neurology 2013

By Joseph Masters (Medical Student, Barts and the London School of Medicine and Dentistry)

 

It is now well established that smokers seem have a reduced risk of Parkinson’s disease and a nice summary of the evidence was published last year [1]. Unfortunately, the detrimental effects of smoking on general health almost certainly outweigh the potential benefits of reducing Parkinson’s disease risk [2].

However, some of the foods we eat – namely peppers, tomatoes and potatoes – contain tiny amounts of nicotine (an active chemical in cigarette smoke) and may suggest protection against Parkinson’s disease in a similar way to smoking, without the harmful side-effects!

The above paper [3] reported that consumption of nicotine containing vegetables (which are members of the Solanaceae family) is associated with a reduced risk of Parkinson’s disease. Some newspapers would have you believe that this is firm evidence that eating peppers can prevent you from developing Parkinson’s – if only it were that simple…

What the authors did:

This was a case-control study, meaning that a group of people recently diagnosed with Parkinson’s disease (cases) were compared with a group of people of similar age and background who did not have Parkinson’s disease (controls). Both groups were asked about their diet and cigarette smoking.

What the paper found:

The controls were found to have significantly higher levels of consumption of all Solanaceae vegetables (peppers, tomatoes and potatoes). However, there was no association between overall vegetable consumption and Parkinson’s disease, so it was just these Solanaceae vegetables which appeared to show a protective effect.

Not all Solanaceae vegetables contain the same amount of nicotine (peppers contain the most and potatoes hardly any at all) and when the authors weighted their calculations to account for the different nicotine concentrations, they found an even stronger association. This suggests that it is the nicotine content of these foods that is driving the protective effect.

Interestingly, when the researchers split the group into ‘ever’ and ‘never’ cigarette smokers, they found that the protective effect of Solanaceae consumption was much greater for non-smokers and, in fact, non-existent for current smokers. This makes sense if it is the nicotine content of these foods which is causing the protective effect, since the nicotine receptors in the brains of smokers will already be occupied by nicotine from their smoke [4], leaving the small amounts of dietary nicotine from peppers unable to have any additional effect.

Limitations of this research:

On the whole, this was good research and there were no major flaws in the study’s methods. The sample size was large enough to produce robust, statistically significant results and the authors adjusted for other known risk factors for Parkinson’s disease such as age, ethnicity, smoking and caffeine consumption. Therefore, it is fair to claim that an association between Solanaceae vegetables and Parkinson’s disease does exist.

However, correlation is not the same as causation and we most definitely cannot yet say that peppers prevent Parkinson’s disease for the following reasons:

The possibility of reverse causality: Parkinson’s disease is known to cause a wide-range of symptoms including loss of smell/taste [5] and heartburn which have been shown to affect patients’ diets [6], and these early features may even occur before Parkinson’s is diagnosed. Therefore, it may simply be the case that people with Parkinson’s (or on track to develop it) favour a plainer diet and are less likely to eat peppers and tomatoes, rather than these foods having a protective effect.

Diet was not assessed for different periods of life: It is likely that consumption of these foods has its effects over several decades but the authors just asked about current dietary patterns.

Replicability: This is the first finding that the nicotine content of food is associated with reduced risk of Parkinson’s disease. Further studies should be done to confirm that the effect really exists.

Poor understanding of the biological basis for the effect: The amounts of nicotine contained in these foods are very, very small relative to the amounts in cigarette smoke and we are uncertain about how much of it actually reaches the brain (much will be removed by the liver en route). We are not even certain whether it is actually the nicotine content of these foods which is producing the protective effect – the authors suggest that other compounds, known as capsinoids or an alkaloid called anantabine might be responsible, but this is all very speculative.

So should I eat more peppers if I want to reduce my risk of Parkinson’s disease?

The authors’ finding that there is an association between Solanaceae consumption and Parkinson’s disease is very interesting. It does not provide unequivocal proof that eating peppers actually prevents Parkinson’s disease! Nonetheless, a ‘Mediterranean style’ diet rich in fruit and vegetables has numerous beneficial health effects and eating a few more tomatoes and peppers every week most certainly cannot do any harm!

References:

[1] Noyce AJ, Bestwick JP, Silveira-Moriyama L, Hawkes CH, Giovannoni G, Lees AJ, et al. Meta-analysis of early nonmotor features and risk factors for Parkinson disease. Ann Neurol. 2012;72:893-901.

[2] The Health Consequences of Smoking: A Report of the Surgeon General. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health; 2004.

[3] Nielsen SS, Franklin GM, Longstreth WT, Swanson PD, Checkoway H. Nicotine from edible Solanaceae and risk of Parkinson disease. Ann Neurol. 2013.

[4] Brody AL, Mandelkern MA, London ED, Olmstead RE, Farahi J, Scheibal D, et al. Cigarette smoking saturates brain alpha 4 beta 2 nicotinic acetylcholine receptors. Arch Gen Psychiatry. 2006;63:907-15.

[5] Shah M, Deeb J, Fernando M, Noyce A, Visentin E, Findley LJ, et al. Abnormality of taste and smell in Parkinson's disease. Parkinsonism Relat Disord. 2009;15:232-7.

[6] Barichella M, Cereda E, Pezzoli G. Major nutritional issues in the management of Parkinson's disease. Mov Disord. 2009;24:1881-92.

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Dopamine Agonist Withdrawal Syndrome: Implications for Patient Care

Drugs Aging. 2013 May 18. [Epub ahead of print]

Nirenberg MJ.

 

Source

Department of Neurology, NYU School of Medicine, New York, NY, USA

 

Abstract

Dopamine agonists are effective treatments for a variety of indications, including Parkinson's disease and restless legs syndrome, but may have serious side effects, such as orthostatic hypotension, hallucinations, and impulse control disorders (including pathological gambling, compulsive eating, compulsive shopping/buying, and hypersexuality). The most effective way to alleviate these side effects is to taper or discontinue dopamine agonist therapy. A subset of patients who taper a dopamine agonist, however, develop dopamine agonist withdrawal syndrome (DAWS), which has been defined as a severe, stereotyped cluster of physical and psychological symptoms that correlate with dopamine agonist withdrawal in a dose-dependent manner, cause clinically significant distress or social/occupational dysfunction, are refractory to levodopa and other dopaminergic medications, and cannot be accounted for by other clinical factors. The symptoms of DAWS include anxiety, panic attacks, dysphoria, depression, agitation, irritability, suicidal ideation, fatigue, orthostatic hypotension, nausea, vomiting, diaphoresis, generalized pain, and drug cravings. The severity and prognosis of DAWS is highly variable. While some patients have transient symptoms and make a full recovery, others have a protracted withdrawal syndrome lasting for months to years, and therefore may be unwilling or unable to discontinue DA therapy. Impulse control disorders appear to be a major risk factor for DAWS, and are present in virtually all affected patients. Thus, patients who are unable to discontinue dopamine agonist therapy may experience chronic impulse control disorders. At the current time, there are no known effective treatments for DAWS. For this reason, providers are urged to use dopamine agonists judiciously, warn patients about the risks of DAWS prior to the initiation of dopamine agonist therapy, and follow patients closely for withdrawal symptoms during dopamine agonist taper.

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Motor outcomes during hospitalization in Parkinson's disease patients: A prospective study

Parkinsonism Relat Disord. 2013 May 13. pii: S1353-8020(13)00162-4. doi: 10.1016/j.parkreldis.2013.04.017. [Epub ahead of print]

Gerlach OH, Broen MP, Weber WE.

Source

Department of Neurology, Orbis Medical Centre, Sittard-Geleen, PO Box 5500, 6130 MB Sittard, The Netherlands.

Abstract

BACKGROUND:

Retrospective studies suggest that many Parkinson's disease patients have a worsening of their motor status during hospitalization. We aimed to quantify this prospectively, and study possible contributing factors.

METHODS:

Over one year we included all consecutive Parkinson's disease patients, newly admitted to a Dutch teaching hospital. We analyzed complications, interventions, and medication distribution. At inclusion and at discharge we assessed the motor status with the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III).

RESULTS:

48% of 46 admitted patients had complications, mainly confusion/delirium (24%) and infections (15%). At discharge 28% of the patients had a worse motor function with a mean increase of more than 5 points on the UPDRS-III. Medication errors occurred in 39%. This is the most important risk factor (p < 0.000) for motor function deterioration, followed by infections during hospitalization, and not being in control of own Parkinson's disease medication. 24% of patients were allowed to take control of their own Parkinson's disease medication, none of these patients did deteriorate.

CONCLUSIONS:

This prospective study shows that a substantial part of hospitalized PD patients has a significant worse motor function at discharge mainly due to medication errors and infections. Quality of care could be improved by addressing preventable errors and allow patients to take control of their own Parkinson's disease medication.

Copyright © 2013 Elsevier Ltd. All rights reserved.

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Combined dementia-risk biomarkers in Parkinson's disease: A prospective longitudinal study

Parkinsonism Relat Disord. 2013 May 2. pii: S1353-8020(13)00125-9. doi: 10.1016/j.parkreldis.2013.03.009. [Epub ahead of print]

Compta Y, Pereira JB, Ríos J, Ibarretxe-Bilbao N, Junqué C, Bargalló N, Cámara A, Buongiorno M, Fernández M, Pont-Sunyer C, Martí MJ.

Source

Parkinson Disease and Movement Disorders Unit, Neurology Service, IDIBAPS, CIBERNED, Hospital Clínic, Barcelona, Catalonia, Spain.

Abstract

Neuropsychological (mostly posterior-cortical) deficits, quantitative magnetic resonance imaging (MRI) atrophy patterns, and low cerebrospinal fluid (CSF) levels of amyloid-β have been separately related to worsening cognition in Parkinson's disease (PD). However, these biomarkers have not been longitudinally assessed in combination as PD-dementia predictors. In this prospective longitudinal study, 27 non-demented PD patients underwent CSF, neuropsychological and 3-T brain-MRI studies at baseline and were re-assessed 18 months later in terms of progression to dementia (primary outcome) and longitudinal neuropsychological and cortical thickness changes (secondary outcomes). At follow-up 11 patients (41%) had progressed to dementia. Lower CSF amyloid-β, worse verbal learning, semantic fluency and visuoperceptual scores, and thinner superior-frontal/anterior cingulate and precentral regions were significant baseline dementia predictors in binary logistic regressions as quantitative and/or dichotomised traits. All participants without baseline biomarker abnormalities remained non-demented whereas all with abnormalities in each biomarker type progressed to dementia, with intermediate risk for those showing abnormalities in a single to two biomarker types (p = 0.006). Both the dementia-outcome and low baseline CSF amyloid-β were prospectively associated with limbic and posterior-cortical neuropsychological decline and frontal, limbic and posterior-cortical thinning from baseline to follow-up. These findings suggest that the combination of CSF amyloid-β, neuropsychological and cortical thickness biomarkers might provide a basis for dementia-risk stratification and progression monitoring in PD.

Longitudinal assessment of tau and amyloid beta in cerebrospinal fluid of Parkinson disease

Acta Neuropathol. 2013 May 4. [Epub ahead of print]

Zhang J, Mattison HA, Liu C, Ginghina C, Auinger P, McDermott MP, Stewart T, Kang UJ; The Parkinson Study Group DATATOP Investigators, Cain KC, Shi M.

Source

Department of Pathology, University of Washington School of Medicine, HMC Box 359635, 325 9th Ave, Seattle, WA, 98104, USA

Abstract

Tau gene has been consistently associated with the risk of Parkinson disease in recent genome wide association studies. In addition, alterations of the levels of total tau, phosphorylated tau [181P], and amyloid beta 1-42 in cerebrospinal fluid have been reported in patients with sporadic Parkinson disease and asymptomatic carriers of leucine-rich repeat kinase 2 mutations, in patterns that clearly differ from those typically described for patients with Alzheimer disease. To further determine the potential roles of these molecules in Parkinson disease pathogenesis and/or in tracking the disease progression, especially at early stages, the current study assessed all three proteins in 403 Parkinson disease patients enrolled in the DATATOP (Deprenyl and tocopherol antioxidative therapy of parkinsonism) placebo-controlled clinical trial, the largest cohort to date with cerebrospinal fluid samples collected longitudinally. These initially drug-naive patients at early disease stages were clinically evaluated, and cerebrospinal fluid was collected at baseline and then at endpoint, defined as the time at which symptomatic anti-Parkinson disease medications were determined to be required. General linear models were used to test for associations between baseline cerebrospinal fluid biomarker levels or their rates of change and changes in the Unified Parkinson Disease Rating Scale (total or part III motor score) over time. Robust associations among candidate markers are readily noted. Baseline levels of amyloid beta were weakly but negatively correlated with baseline Unified Parkinson Disease Rating Scale total scores. Baseline phosphorylated tau/total tau and phosphorylated tau/amyloid beta were significantly and negatively correlated with the rates of the Unified Parkinson Disease Rating Scale change. While medications (deprenyl and/or tocopherol) did not appear to alter biomarkers appreciably, a weak but significant positive correlation between the rate of change in total tau or total tau/amyloid beta levels and the change of the Unified Parkinson Disease Rating Scale was observed. Notably, these correlations did not appear to be influenced by APOE genotype. These results are one of the very first pieces of evidence suggesting that tau and amyloid beta are critically involved in early Parkinson disease progression, potentially by a different mechanism than that in Alzheimer disease, although their applications as Parkinson disease progression markers will likely require the addition of other proteins.

Motor and non-motor symptoms of 1453 patients with Parkinson's disease: Prevalence and risks

Parkinsonism Relat Disord. 2013 Apr 29. pii: S1353-8020(13)00133-8. doi: 10.1016/j.parkreldis.2013.04.001. [Epub ahead of print]

Yoritaka A, Shimo Y, Takanashi M, Fukae J, Hatano T, Nakahara T, Miyamato N, Urabe T, Mori H, Hattori N.

Source

Department of Neurology, Juntendo University School of Medicine, Japan; Department of Neurology, Juntendo University Koshigaya Hospital, Japan.

Abstract

PURPOSE:

We examined the prevalence and risk of clinical symptoms in a large number of Japanese patients with Parkinson's disease (PD) (n = 1453; 650 males).

METHODS:

Events were analyzed using Kaplan-Meier survival curves, logistic regression, and Cox proportional-hazards models.

RESULTS:

The mean age (SD) was 67.7 (10.0), age of onset was 58.0 (11.5), and disease duration was 9.7 (6.6) years. The mean modified Hoehn and Yahr stage was 2.8 (1.2). Most patients (88.9%) received levodopa (547.7 (257.6) mg/day). A large proportion (81.3%) received dopamine agonists (136.2 (140.7) mg/day). About 23.4% received pain treatment 6.9 (5.1) years after the onset; females (p < 0.05) and patients with late-onset PD (≥60 years, p < 0.001) were more likely to be affected. About 44.7% of patients had wearing-off 7.5 (4.7) years after the onset, and it was more common in females (p < 0.001) and patients with early-onset PD (p < 0.001). Camptocormia was found in 9.5% of patients 8.1 (6.2) years after the onset, and it was more common in females (p < 0.05) and patients with late-onset PD (p < 0.05). About 28.6% of patients developed psychosis 9.0 (5.4) years after the onset, and it was more likely to occur in patients with late-onset PD (p < 0.001). Late-onset PD and cerebrovascular disease were also associated with increased risk of pneumonia.

CONCLUSIONS:

Considering that very few studies have assessed numerous clinical symptoms in the same report, these data provide a useful reference for the clinical course of PD.

Copyright © 2013 Elsevier Ltd. All rights reserved.

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An accelerometry-based study of lower and upper limb tremor in Parkinson's disease

J Clin Neurosci. 2013 Apr 29. pii: S0967-5868(12)00570-X. doi: 10.1016/j.jocn.2012.06.015. [Epub ahead of print]

Scanlon BK, Levin BE, Nation DA, Katzen HL, Guevara-Salcedo A, Singer C, Papapetropoulos S.

Source

Sierra-Pacific Mental Illness Research, Education, and Clinical Center, VA Palo Alto Health Care System, 3801 Miranda Ave, (151Y), Palo Alto, CA 94304, United States; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, United States.

Abstract

Over the past two decades, several studies have aimed to quantify the kinetic properties of tremor with primary focus on the upper limbs. However, there is a lack of investigation into the properties of tremor in the lower limbs. The objective of this preliminary study was to investigate the properties of oscillatory movement, at rest and in posture, in both the upper and lower limbs of Parkinson's disease (PD) patients with clinically undetectable to modest rest/postural tremor and healthy controls. PD patients (N=16) and controls (N=8) were examined clinically by a movement disorders specialist and oscillatory movements in all four extremities were evaluated using a portable biaxial accelerometer. While tremor intensity and frequency did not differ between groups, the intraindividual variability of rest and postural tremor frequency in the dexterity-dominant lower limb was lower in people living with PD than in healthy adults. Additionally, rest tremor frequency was discrepant between upper and lower limbs in PD. Our work introduces the possibility that minute variations in lower limb movements, which are imperceptible upon expert clinical exam, can be used to differentiate a diseased sample from a healthy one. These preliminary findings suggest that additional work using objective tremor measurement may improve our understanding of lower limb motor dysfunction in PD and lead to the refinement of current, and the development of new, metrics to enhance early diagnosis, differential diagnosis, and symptom quantification.

Published by Elsevier Ltd.

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Cerebral white matter hyperintensity in Parkinson's disease: A major risk factor for mild cognitive impairment

Parkinsonism Relat Disord. 2013 Apr 24. pii: S1353-8020(13)00124-7. doi: 10.1016/j.parkreldis.2013.03.008. [Epub ahead of print]

Kandiah N, Mak E, Ng A, Huang S, Au WL, Sitoh YY, Tan LC.

Source

Department of Neurology, National Neuroscience Institute, Singapore; Duke-NUS Graduate Medical School, Singapore.

Abstract

BACKGROUND:

Mild cognitive impairment (MCI) and dementia contribute to a poor quality of life among patients with PD. The influence of cerebral ischemia as a risk factor for MCI in PD has not been adequately investigated. To address this issue, we examined the influence of the volume and distribution of white matter hyperintensity (WMH) as a risk factor for MCI in early PD.

METHODS:

Prospective study of patients with early idiopathic PD. All patients had baseline MRI-FLAIR, clinical assessment and detailed neuropsychological evaluation. Data on demographics, vascular risk factors, cognitive performance and WMH volumes were analyzed.

RESULTS:

91 patients; mean age 64.9 years, mean education of 10.5 years. 24 patients fulfilled the Movement Disorder Society criteria for MCI and were classified as PD-MCI while the rest were classified as PD with no cognitive impairment (PD-NCI). Patients with PD-MCI and PD-NCI did not differ in Hoehn & Yahr staging. PD-MCI patients had a higher prevalence of diabetes mellitus, hypertension and hyperlipidemia. PD-MCI patients had significantly greater volume of periventricular (6.04 ml vs. 2.66 ml, p = 0.001) and deep subcortical WMH (2.16 vs.1.44, p = 0.002). Regional WMH was significantly greater among PD-MCI in the frontal, parietal and occipital regions. Logistic regression analyses demonstrated WMH to be associated with PD-MCI independent of age, education, and vascular risk factors. Increasing WMH volume was associated with lower performance on executive function, memory and language.

CONCLUSIONS:

WMH is an important risk factor for PD-MCI independent of vascular risk factors. PD patients with WMH should be regularly screened for MCI.

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Impulsivity and apathy in Parkinson's disease

J Neuropsychol. 2013 Apr 29. doi: 10.1111/jnp.12013. [Epub ahead of print]

Sinha N, Manohar S, Husain M.

Source

Nuffield Department of Clinical Neurosciences and Department of Experimental Psychology, Oxford University, Oxford, UK; Institute of Cognitive Neuroscience, University College London, UK; Institute of Neurology, University College London, UK.

Abstract

Impulse control disorders (ICDs) and apathy are recognized as two important neuropsychiatric syndromes associated with Parkinson's disease (PD), but as yet we understand very little about the cognitive mechanisms underlying them. Here, we review emerging findings, from both human and animal studies, that suggest that impulsivity and apathy are opposite extremes of a dopamine-dependent spectrum of motivated decision making. We first argue that there is strong support for a hypodopaminergic state in PD patients with apathy, as well as for an association between dopamine therapy and development of ICDs. However, there is little evidence for a clear dose-response relationship, and great heterogeneity of findings. We argue that dopaminergic state on its own is an insufficient explanation, and suggest instead that there is now substantial evidence that both apathy and impulsivity are in fact multi-dimensional syndromes, with separate, dissociable mechanisms underlying their 'surface' manifestations. Some of these mechanisms might be dopamine-dependent. According to this view, individuals diagnosed as impulsive or apathetic may have very different mechanisms underlying their clinical states. We propose that impulsivity and apathy can arise from dissociable deficits in option generation, option selection, action initiation or inhibition and learning. Review of the behavioural and neurobiological evidence leads us to a new conceptual framework that might help understand the variety of functional deficits seen in PD.

© 2013 The British Psychological Society.

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Factors predictive of the development of levodopa-induced dyskinesia and wearing-off in Parkinson's disease

Mov Disord. 2013 Apr 29. doi: 10.1002/mds.25364. [Epub ahead of print]

Warren Olanow C, Kieburtz K, Rascol O, Poewe W, Schapira AH, Emre M, Nissinen H, Leinonen M, Stocchi F; Stalevo Reduction in Dyskinesia Evaluation in Parkinson's Disease (STRIDE-PD) Investigators.

Source

Department of Neurology and Neuroscience, Mount Sinai School of Medicine, New York, NY, USA; Institute for Research, Scientific Institute for Care and Treatment, San Raffaele, Rome, Italy.

Abstract

The Stalevo Reduction in Dyskinesia Evaluation in Parkinson's Disease (STRIDE-PD) study compared the initiation of levodopa (l-dopa) therapy with l-dopa/carbidopa (LC) versus l-dopa/carbidopa/entacapone (LCE) in patients with Parkinson's disease. In the current study, the STRIDE-PD study population was investigated to determine the effect of l-dopa dose and other risk factors on the development of dyskinesia and wearing-off. Patients were randomized to receive LCE (n=373) or LC (n=372). Blinded assessments for dyskinesia and wearing-off were performed at 3-month intervals for the 134- to 208-week duration of the study. The patients were divided into 4 dose groups based on nominal l-dopa dose at the time of onset of dyskinesia (or at study conclusion if there was no dyskinesia): group 1, <400 mg/day (n=157); group 2, 400 mg/day (n=310); group 3, 401 to 600 mg/day (n=201); and group 4, >600 mg/day (n=77). Similar analyses were performed with respect to wearing-off and any motor complication. The times to onset and frequency of dyskinesia, wearing-off, or any motor complication were compared using the log-rank test (overall trend test) and a Cox proportional hazards model (pairwise comparisons). A stepwise Cox proportional hazards model was used to screen predictive factors in a multivariate analysis. The risk of developing dyskinesia and wearing-off increased in an l-dopa dose-dependent manner (P<0.001 for both). Analyses using l-dopa equivalent doses produced comparable results. Factors that were predictive of dyskinesia, in rank order, were: young age at onset, higher l-dopa dose, low body weight, North American geographic region, LCE treatment group, female gender, and more severe Unified Parkinson's Disease Rating Scale (UPDRS) Part II. Multivariate analyses identified similar predictors for wearing-off but included baseline UPDRS Part III and excluded weight and treatment allocation. The risk of developing dyskinesia or wearing-off was closely linked to l-dopa dose. The current results suggest that physicians should use the lowest dose of l-dopa that provides satisfactory clinical control to minimize the risk of both dyskinesia and wearing-off.

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