"PSP is one of the atypical Parkinsonian disorders..."

"... It is often confused with Parkinson's disease but has some key features which make it different. Like people with Parkinson's disease, those with PSP are in desperate need of treatments that can help ease their suffering and ultimately offer a cure."

"This is an short film about what life is like for patients with PSP and those that care for them."

- Alastair Noyce

Risk factors for dementia with Lewy bodies: A case-control study

Neurology. 2013 Jul 26. [Epub ahead of print]

Boot BP, Orr CF, Ahlskog JE, Ferman TJ, Roberts R, Pankratz VS, Dickson DW, Parisi J, Aakre JA, Geda YE, Knopman DS, Petersen RC, Boeve BF.

Source

From the Departments of Neurology (B.P.B, C.F.O., J.E.A., Y.E.G., D.S.K., R.C.P., B.F.B.), Psychiatry and Psychology (T.J.F., Y.E.G.), Health Sciences Research (R.R., V.S.P., J.A.A., Y.E.G.), Anatomic Pathology (D.W.D.), and Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program of the Mayo Foundation (B.P.B., C.F.O., Y.E.G., D.S.K., R.C.P., B.F.B.), Mayo Clinic College of Medicine, Rochester MN, Scottsdale, AZ, and Jacksonville FL. B.P.B. is currently affiliated with the Neurology Department, Brigham and Women's Hospital, Boston, MA. C.F.O. is currently affiliated with Macquarie Neurology, Macquarie University Hospital, NSW, Australia.

Abstract

OBJECTIVE:

To determine the risk factors associated with dementia with Lewy bodies (DLB).

METHODS:

We identified 147 subjects with DLB and sampled 2 sex- and age-matched cognitively normal control subjects for each case. We also identified an unmatched comparison group of 236 subjects with Alzheimer disease (AD). We evaluated 19 candidate risk factors in the study cohort.

RESULTS:

Compared with controls, subjects with DLB were more likely to have a history of anxiety (odds ratio; 95% confidence interval) (7.4; 3.5-16; p < 0.0001), depression (6.0; 3.7-9.5; p < 0.0001), stroke (2.8; 1.3-6.3; p = 0.01), a family history of Parkinson disease (PD) (4.6; 2.5-8.6; p < 0.0001), and carry APOE ε4 alleles (2.2; 1.5-3.3; p < 0.0001), but less likely to have had cancer (0.44; 0.27-0.70; p = 0.0006) or use caffeine (0.29; 0.14-0.57; p < 0.0001) with a similar trend for alcohol (0.65; 0.42-1.0; p = 0.0501). Compared with subjects with AD, subjects with DLB were younger (72.5 vs 74.9 years, p = 0.021) and more likely to be male (odds ratio; 95% confidence interval) (5.3; 3.3-8.5; p < 0.0001), have a history of depression (4.3; 2.4-7.5; p < 0.0001), be more educated (2.5; 1.1-5.6; p = 0.031), have a positive family history of PD (5.0; 2.4-10; p < 0.0001), have no APOE ε4 alleles (0.61; 0.40-0.93; p = 0.02), and to have had an oophorectomy before age 45 years (7.6; 1.5-39; p = 0.015).

CONCLUSION:

DLB risk factors are an amalgam of those for AD and PD. Smoking and education, which have opposing risk effects on AD and PD, are not risk factors for DLB; however, depression and low caffeine intake, both risk factors for AD and PD, increase risk of DLB more strongly than in either.

Epidemiology of dementia with Lewy bodies--the Alzheimer-Parkinson overlap

Neurology. 2013 Jul 26. [Epub ahead of print]

Postuma RB.

Abstract

Dementia with Lewy bodies (DLB) is viewed by many as a condition that combines features of Alzheimer disease (AD) and Parkinson disease (PD). Autopsy in DLB discloses both amyloid and synuclein deposition, and the relative degree of each may determine the clinical phenotype.1 Despite being the second most common form of dementia, risk factors of DLB have never been systematically studied. The current report by Boot et al.2 therefore represents a considerable advance. Relying on data from 3 separate cohorts, the authors found that the risk factor profile of DLB appeared to combine aspects of AD and PD. Known risk factors for PD, such as nonuse of caffeine, anxiety, depression, and family history of PD were present in DLB. Similarly, AD risk factors such as APOE status, depression, and stroke were also present in DLB. Smoking, a protective factor for PD and a risk factor for AD, was not associated with DLB, perhaps suggesting that the risk factors "canceled out." However, when risk factors were common between conditions (depression and caffeine use), the relationship in DLB appeared to be stronger than for AD or PD individually, suggesting additive risks. Although the risk factors were not always comprehensively assessed and diagnosis was clinical in the majority of cases (albeit with broadly similar results in the subgroup with autopsy confirmation), the study is well-designed and comprehensively analyzed. In addition to providing for the first time a broad picture of risk factors for DLB, the study reinforces the close interactions among DLB, PD, and AD, and points to the potential importance of multiple interacting pathologies in determining clinical disease.

Surgical treatment of Parkinson disease: past, present, and future

Neurol Clin. 2013 Aug;31(3):799-808. doi: 10.1016/j.ncl.2013.03.007. Epub 2013 Apr 4.

Duker AP, Espay AJ.

Source

Department of Neurology and Rehabilitation Medicine, James J. and Joan A. Gardner Center for Parkinson's Disease and Movement Disorders, University of Cincinnati Neuroscience Institute, University of Cincinnati, 260 Stetson Street, Suite 2300, Cincinnati, OH 45267-0525, USA.

Abstract

Advances in functional neurosurgery have expanded the treatment of Parkinson disease (PD) to targeted electrical stimulation of specific nodes in the basal ganglia circuitry. Deep brain stimulation (DBS), applied to selected patients and difficult-to-manage motor fluctuations, yields substantial reductions in off time and dyskinesia. Emerging concepts in DBS include examination of new targets, such as the potential efficacy of pedunculopontine nucleus stimulation for treatment of freezing and falls, the use of pathologic oscillations in the beta band to construct an adaptive "closed-loop" DBS, and new technologies, including segmented electrodes to steer current toward specific neural populations.

Cognitive impairment and PD patients' capacity to consent to research

Neurology. 2013 Jul 26. [Epub ahead of print]

Karlawish J, Cary M, Moelter ST, Siderowf A, Sullo E, Xie S, Weintraub D.

Source

From the University of Pennsylvania (J.K., M.C., E.S., S.X., D.W.), Department of Medicine (J.K., E.S.), Department of Medical Ethics and Health Policy (J.K.), Alzheimer's Disease Center (J.K.), Neurodegenerative Disease Ethics and Policy Program (J.K., E.S.), Leonard Davis Institute of Health Economics (J.K.), Center for Clinical Epidemiology and Biostatistics (M.C., S.X.), Department of Psychiatry (D.W.), Parkinson's Disease (D.W.) and Mental Illness (D.W.) Research, Education and Clinical Centers; University of the Sciences in Philadelphia (S.T.M.); and Avid Radiopharmaceuticals (A.S.), Philadelphia, PA.

Abstract

OBJECTIVE:

To examine how cognitive impairment affects Parkinson disease (PD) patients' research consent capacity.

METHODS:

A cross-sectional study of 90 patients with PD, divided using Mattis Dementia Rating Scale-2 scores into 3 groups of 30 (normal, borderline, and impaired), and 30 neurologically normal older adults completed 2 capacity interviews (an early-phase randomized and controlled drug trial and a sham-controlled surgical implantation of genetic tissue) using the MacArthur Competence Assessment Tool for Clinical Research. Expert clinicians used the interviews to classify the patients as either capable or not capable of providing their own informed consent. These judgments were compared with performance on the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE).

RESULTS:

Cognitively normal PD patients typically scored well on the capacity measures. In contrast, patients with impaired cognition were not capable of providing their own informed consent: 17% (5/30) on the drug trial and 3% (1/30) on the surgery trial were judged capable. Patients with borderline impairment showed adequate performance on measures of appreciation and reasoning, but impaired performance on understanding the drug trial compared with normal controls and normal PD patients, and on understanding the surgery trial compared with normal controls. Sixty-seven percent (20/30) on the drug trial and 57% (17/30) on the surgery trial were judged capable of consent. Receiver operating characteristic analyses showed that the MMSE and MoCA could detect the likelihood of impaired capacity, with the MoCA demonstrating greater sensitivity.

CONCLUSIONS:

PD patients with borderline cognitive impairment have impairments in their decisional capacity. The MoCA may be useful to identify the patients at risk of impaired capacity.

Simple decision aid for those newly diagnosed with Parkinson's

"I prepared this graph to help newly diagnosed Parkinson's patients share their treatment choices with their doctor. Happy to hear feedback - is it helpful or unhelpful?"

- Alastair Noyce

Rapid eye movement sleep behavior disorder: devising controlled active treatment studies for symptomatic and neuroprotective therapy-a consensus statement from the International Rapid Eye Movement Sleep Behavior Disorder Study Group.

Sleep Med. 2013 Jul 22. pii: S1389-9457(13)00175-5. doi: 10.1016/j.sleep.2013.02.016. [Epub ahead of print]

Schenck CH, Montplaisir JY, Frauscher B, Hogl B, Gagnon JF, Postuma R, Sonka K, Jennum P, Partinen M, Arnulf I, Cochen de Cock V, Dauvilliers Y, Luppi PH, Heidbreder A, Mayer G, Sixel-Döring F, Trenkwalder C, Unger M, Young P, Wing YK, Ferini-Strambi L, Ferri R, Plazzi G, Zucconi M, Inoue Y, Iranzo A, Santamaria J, Bassetti C, Moeller JC, Boeve BF, Lai YY, Pavlova M, Saper C, Schmidt P, Siegel JM, Singer C, St Louis E, Videnovic A, Oertel W.

Source

Minnesota Regional Sleep Disorders Center, Department of Psychiatry, Hennepin County Medical Center and University of Minnesota Medical School, Minneapolis, MN, USA.

Abstract

OBJECTIVES:

We aimed to provide a consensus statement by the International Rapid Eye Movement Sleep Behavior Disorder Study Group (IRBD-SG) on devising controlled active treatment studies in rapid eye movement sleep behavior disorder (RBD) and devising studies of neuroprotection against Parkinson disease (PD) and related neurodegeneration in RBD.

METHODS:

The consensus statement was generated during the fourth IRBD-SG symposium in Marburg, Germany in 2011. The IRBD-SG identified essential methodologic components for a randomized trial in RBD, including potential screening and diagnostic criteria, inclusion and exclusion criteria, primary and secondary outcomes for symptomatic therapy trials (particularly for melatonin and clonazepam), and potential primary and secondary outcomes for eventual trials with disease-modifying and neuroprotective agents. The latter trials are considered urgent, given the high conversion rate from idiopathic RBD (iRBD) to Parkinsonian disorders (i.e., PD, dementia with Lewy bodies [DLB], multiple system atrophy [MSA]).

RESULTS:

Six inclusion criteria were identified for symptomatic therapy and neuroprotective trials: (1) diagnosis of RBD needs to satisfy the International Classification of Sleep Disorders, second edition, (ICSD-2) criteria; (2) minimum frequency of RBD episodes should preferably be ⩾2 times weekly to allow for assessment of change; (3) if the PD-RBD target population is included, it should be in the early stages of PD defined as Hoehn and Yahr stages 1-3 in Off (untreated); (4) iRBD patients with soft neurologic dysfunction and with operational criteria established by the consensus of study investigators; (5) patients with mild cognitive impairment (MCI); and (6) optimally treated comorbid OSA. Twenty-four exclusion criteria were identified. The primary outcome measure for RBD treatment trials was determined to be the Clinical Global Impression (CGI) efficacy index, consisting of a four-point scale with a four-point side-effect scale. Assessment of video-polysomnographic (vPSG) changes holds promise but is costly and needs further elaboration. Secondary outcome measures include sleep diaries; sleepiness scales; PD sleep scale 2 (PDSS-2); serial motor examinations; cognitive indices; mood and anxiety indices; assessment of frequency of falls, gait impairment, and apathy; fatigue severity scale; and actigraphy and customized bed alarm systems. Consensus also was established for evaluating the clinical and vPSG aspects of RBD. End points for neuroprotective trials in RBD, taking lessons from research in PD, should be focused on the ultimate goal of determining the performance of disease-modifying agents. To date no compound with convincing evidence of disease-modifying or neuroprotective efficacy has been identified in PD. Nevertheless, iRBD patients are considered ideal candidates for neuroprotective studies.

CONCLUSIONS:

The IRBD-SG provides an important platform for developing multinational collaborative studies on RBD such as on environmental risk factors for iRBD, as recently reported in a peer-reviewed journal article, and on controlled active treatment studies for symptomatic and neuroprotective therapy that emerged during the 2011 consensus conference in Marburg, Germany, as described in our report.

Drug-induced Parkinson`s disease. A clinical review

Neurosciences (Riyadh). 2013 Jul;18(3):215-21.

Bohlega SA, Al-Foghom NB.

Source

Section of Neurology, Department of Neurosciences, King Faisal Specialist Hospital and Research Centre, PO Box 3354, Riyadh 11211, Kingdom of Saudi Arabia.

Abstract

Drug-induced Parkinsonism must always be suspected when parkinsonian symptom like rigidity, tremor, or postural instability appear in patients receiving drug treatment. Indeed, drug-induced Parkinsonism is a frequent etiology of secondary Parkinsonism. The main causative drugs are antipsychotic, other neuroleptic drugs, and calcium-channel entry blockers. The risk associated with antipsychotics is often dose dependent and related to dopamine D2 striatal occupancy. The risk is less for the second-generation atypical antipsychotic. The other treatments rarely involved are antidepressants, antivirals, anti-arrhythmics, lithium, valproic acid, and others. Regression of symptom will be observed in most cases after a mean delay of 3 months after cessation of treatment. In one-tenth of cases, symptoms persist after drug withdrawal leading to the diagnosis of underlined idiopathic Parkinson`s disease.

Update on diffusion MRI in Parkinson's disease and atypical parkinsonism

J Neurol Sci. 2013 Jul 15. pii: S0022-510X(13)00310-9. doi: 10.1016/j.jns.2013.06.032. [Epub ahead of print]

Meijer FJ, Bloem BR, Mahlknecht P, Seppi K, Goraj B.

Source

Radboud University Nijmegen Medical Centre, Department of Radiology, Nijmegen, The Netherlands. 

Abstract

Differentiating Parkinson's disease (PD) from other types of neurodegenerative atypical parkinsonism (AP) can be challenging, especially in early disease stages. Routine brain magnetic resonance imaging (MRI) can show atrophy or signal changes in several parts of the brain with fairly high specificity for particular forms of AP, but the overall diagnostic value of routine brain MRI is limited. In recent years, various advanced MRI sequences have become available, including diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI). Here, we review available literature on the value of diffusion MRI for identifying and quantifying different patterns of neurodegeneration in PD and AP, in relation to what is known of underlying histopathologic changes and clinical presentation of these diseases. Next, we evaluate the value of diffusion MRI to differentiate between PD and AP and the potential value of serial diffusion MRI to monitor disease progression. We conclude that diffusion MRI may quantify patterns of neurodegeneration which could be of additional value in clinical use. Future prospective clinical cohort studies are warranted to assess the added diagnostic value of diffusion MRI.

Relationship of olfactory function with olfactory bulbus volume, disease duration and Unified Parkinson's disease rating scale scores in patients with early stage of idiopathic Parkinson's disease

J Clin Neurosci. 2013 Jul 16. pii: S0967-5868(13)00109-4. doi: 10.1016/j.jocn.2012.11.017. [Epub ahead of print]

Hakyemez HA, Veyseller B, Ozer F, Ozben S, Bayraktar GI, Gurbuz D, Cetin S, Yildirim YS.

Source

Haseki Training and Research Hospital, Department of Neurology, Istanbul, Turkey.

Abstract

We aimed to investigate the relationship between olfactory function and olfactory bulbus (OB) volume, disease duration and Unified Parkinson's disease rating scale (UPDRS) scores in early stage idiopathic Parkinson's disease patients. The University of Pennsylvania Smell Identification Test (UPSIT) was used for the evaluation of olfactory function. UPSIT scores for patients with Parkinson's disease were significantly lower than controls. There was no significant difference between stage 1 and stage 2 patients. OB volumes were higher in stage 1 and 2 patients than controls, but there was no statistical difference between the three groups. No significant correlation was found between UPSIT and UPDRS total scores, nor between UPSIT scores and disease duration in stage 1 and 2 patients. According to our results, we propose UPSIT be used as a screening test to diagnose presymptomatic patients, but not OB volumes.

Nicotine increases lifespan and rescues olfactory and motor deficits in a Drosophila model of Parkinson's disease

Behav Brain Res. 2013 Jul 16. pii: S0166-4328(13)00419-1. doi: 10.1016/j.bbr.2013.07.020. [Epub ahead of print]

Chambers RP, Call GB, Meyer D, Smith J, Techau JA, Pearman K, Buhlman LM.

Source

Department of Biomedical Sciences, College of Health Sciences, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ 85308, United States.

Abstract

Drosophila melanogaster is an attractive model of familial Parkinson's disease, as flies with loss-of-function mutations of the parkin gene exhibit many pathologies observed in PD patients. Progressive motor deficits found in homozygous parkin mutants seem to result from mitochondrial pathology that causes indirect flight muscle and dopaminergic neuronal degeneration [1,2]. We have found that heterozygous parkin mutants have decreased lifespan, generally progressive motor dysfunction and olfactory deficits compared to control flies, suggesting that mutation of this gene produces a dominant phenotype. Tobacco smokers are dose-dependently less likely to develop PD [3-5]; subsequent in vitro and in vivo studies show that nicotine is protective in models of sporadic PD [6]. Literature addressing the potential protection by nicotine in Parkin loss-of-function models spans limited concentrations and selected time points in the organism's lifespan. We have found that parkin heterozygotes have late-onset climbing and flying deficits as well as decreased viability and olfactory deficits that precede motor defects. While chronic nicotine exposure decreases lifespan and climbing and flying abilities in control flies, it can improve viability and flying capability as well as rescue climbing and olfactory deficits in parkin heterozygotes. Dopaminergic neurons are spared in the parkin heterozygote, perhaps because this phenotype is less severe than in the homozygous parkin mutants. Nicotine pretreatment may be protective in sporadic PD patients and models; however, timely diagnosis remains to be an obstacle. Our results suggest that nicotine also may be protective in familial PD patients, who can be easily identified before motor symptoms occur.