Parkinson's Disease

Psychosocial interventions for non-professional carers of people with Parkinson's Disease: a scoping review.

by Susanne Hempel

Centre for Reviews and Dissemination. Psychosocial interventions for non-professional carers of people with Parkinson's Disease: a scoping review. CRD Report 37. York: University of York. 2007

The Centre for Reviews and Dissemination (CRD), based at the University of York was commissioned by the Parkinson’s... more The Centre for Reviews and Dissemination (CRD), based at the University of York was commissioned by the Parkinson’s Disease Society to undertake a scoping review to map the available evidence on interventions for carers.
The aim is to provide an overview of existing research on the effectiveness and cost-effectiveness of psychosocial interventions for non-professional carers of people with Parkinson’s disease. 
The results of this scoping review can be used to inform decisions about research priorities. The map of the existing literature aims to enable the Parkinson’s Disease Society to focus resources on areas that currently do not have a strong evidence base and would benefit from further research.

Cooperative genome-wide analysis shows increased homozygosity in early onset Parkinson's disease

by Laura Kilarski

Apathy in Parkinson's disease

by Graham Pluck

Doctor, is it Parkinson's disease?

by Lars Wojtecki

Diagnostic accuracy of combined FP-CIT, IBZM, and MIBG scintigraphy in the differential diagnosis of degenerative parkinsonism: a multidimensional statistical approach

by Lars Wojtecki

Melzer, T. R., Watts, R., MacAskill, M. R., Pitcher, T. L., Livingston, L., Keenan, R., . . . Anderson, T. J. (2012). Grey matter atrophy in cognitively impaired Parkinson’s disease. Journal of Neurology, Neurosurgery & Psychiatry, 83(2), 188-194. doi:10.1136/jnnp-2011-30082

by Michael MacAskill

Objective Mild cognitive impairment and dementia are common non-motor features of Parkinson’s disease (PD). The aim of... more Objective Mild cognitive impairment and dementia are common non-motor features of Parkinson’s disease (PD). The aim of this study was to characterise grey matter changes associated with clearly defined stages of cognitive impairment in PD using structural MRI. Methods 96 PD subjects were classified using detailed cognitive testing as PD with normal cognition (PD-N, n¼57), PD with mild cognitive impairment (PD-MCI, n¼23) or PD with dementia (PD-D, n¼16); 34 controls matched for mean age and sex ratio also participated. Grey matter volume differences were evaluated using voxel based morphometry of grey matter segments derived from T1 weighted 3 T MRI, and multiple linear regression assessed the relationship between cognitive and motor impairments and grey matter concentration. Results Compared with controls, no grey matter differences were found in PD-N. PD-MCI showed limited grey matter atrophy in the temporal, parietal and frontal cortex as well as the bilateral caudal hippocampus, amygdala and right putamen. PD-D subjects exhibited far more extensive atrophy in regions involved in PD-MCI but also had reduced grey matter volume in other large areas of the temporal lobe (including the parahippocampi), the intracalcarine and lingual gyri, posterior cingulate gyrus, frontal regions and bilateral caudate. Grey matter loss in PD correlated with global cognitive score but not motor impairment in most of these regions. Interpretation Marked grey matter atrophy occurs in PD with dementia but far less extensive changes are evident in PD-MCI. Some grey matter atrophy precedes the development of dementia but may be accelerated once frank dementia begins.

van Stockum, S., MacAskill, M. R., & Anderson, T. J. (2011). Bottom-up effects modulate saccadic latencies in well-known eye movement paradigm. Psychological Research, 75, 272-278. doi:10.1007/s00426-010-0305-

by Michael MacAskill

A well-known eye movement paradigm com-bines saccades (fast eye movements) with a perceptual dis-crimination task. At... more A well-known eye movement paradigm com-bines saccades (fast eye movements) with a perceptual dis-crimination task. At a variable time after the onset of a central arrow cue indicating the target direction [the stimu-lus onset asynchrony (SOA)], discrimination symbols appear brieXy at saccade target and non-target locations. A previous study revealed an unexpected eVect of SOA on saccadic latencies: latencies were longer in trials with longer SOAs. It was suggested that this eVect reXects a top-down process as observers may wait for the discrimination symbol to appear before executing saccades. However, symbol onsets may also modulate saccade latencies from the bottom-up. To clarify the origin of the SOA eVect on latencies in this paradigm, we used a simpliWed version of the original task plus two new symbol onset conditions for comparison. The results indicate that the modulation of saccadic latencies was not due to a top-down strategy, but to a combination of two opposing bottom-up eVects: the symbol onsets at the target location shortened saccade latencies, while symbol onsets at non-target locations lengthened saccade latencies.

Speech and language therapy versus placebo or no intervention for speech problems in Parkinson's disease

by Marian Brady

Clare P Herd, Claire L Tomlinson, Katherine HO Deane, Marian C Brady, Christina H Smith, Catherine Sackley, Carl E Clarke

Background
Parkinson's disease patients commonly suffer from speech and vocal problems including dysarthric... more Background
Parkinson's disease patients commonly suffer from speech and vocal problems including dysarthric speech, reduced loudness and loss of articulation. These symptoms increase in frequency and intensity with progression of the disease). Speech and language therapy (SLT) aims to improve the intelligibility of speech with behavioural treatment techniques or instrumental aids.

Objectives
To compare the efficacy of speech and language therapy versus placebo or no intervention for speech and voice problems in patients with Parkinson's disease.

Search methods
Relevant trials were identified by electronic searches of numerous literature databases including MEDLINE, EMBASE, and CINAHL, as well as handsearching of relevant conference abstracts and examination of reference lists in identified studies and other reviews. The literature search included trials published prior to 11th April 2011.

Selection criteria
Only randomised controlled trials (RCT) of speech and language therapy versus placebo or no intervention were included.

Data collection and analysis
Data were abstracted independently by CH and CT and differences settled by discussion.

Main results
Three randomised controlled trials with a total of 63 participants were found comparing SLT with placebo for speech disorders in Parkinson's disease. Data were available from 41 participants in two trials. Vocal loudness for reading a passage increased by 6.3 dB (P = 0.0007) in one trial, and 11.0 dB (P = 0.0002) in another trial. An increase was also seen in both of these trials for monologue speaking of 5.4 dB (P = 0.002) and 11.0 dB (P = 0.0002), respectively. It is likely that these areclinically significant improvements. After six months, patients from the first trial were still showing a statistically significant increase of 4.5 dB (P = 0.0007) for reading and 3.5 dB for monologue speaking. Some measures of speech monotonicity and articulation were investigated; however, all these results were non-significant.

Authors' conclusions
Although improvements in speech impairments were noted in these studies, due to the small number of patients examined, methodological flaws , and the possibility of publication bias, there is insufficient evidence to conclusively support or refute the efficacy of SLT for speech problems in Parkinson's disease. A large well designed placebo-controlled RCT is needed to demonstrate SLT's effectiveness in Parkinson's disease. The trial should conform to CONSORT guidelines. Outcome measures with particular relevance to patients with Parkinson’s disease should be chosen and patients followed for at least six months to determine the duration of any improvement.

Word processing in Parkinson's disease is impaired for action verbs but not for concrete nouns

by Veronique Boulenger

Implicit and explicit emotional processing in Parkinson's disease

by Nathalie Bedoin

Introduction: Our study investigated the ability of nondemented Parkinson’s disease (PD) patients to explicitlymore Introduction: Our study investigated the ability of nondemented Parkinson’s disease (PD) patients to explicitly
identify emotional words and to show implicit sensitivity to these emotions in a task that did not require emotional
processing. Methods: Twelve PD patients and 12 healthy controls, matched for age and education, performed lexical
decision (LD) and emotional categorisation tasks (fear, disgust, and happiness) on the same words. Results:
PD patients were specifically impaired in the explicit identification of disgust with a decreased accuracy in LD.
However, a slowdown in LD latency in both PD patients and the control group suggested the persistence of
emotional sensitivity to disgust. Conclusion: Despite the persistence of an automatic capture by the emotional
content of disgust, PD patients may suffer from emotional deficits in recognising both the emotional and semantic
components of words, resulting in blunted emotional responses.

Determination of the free energy landscape of α-synuclein using spin label nuclear magnetic resonance measurements

by Jane Allison

Pallidotomy does not ameliorate abnormal intracortical inhibition in Parkinson’s disease.

by Martin Sale

Association of Sequence Alterations in the Putative Promoter of RAB7L1 With a Reduced Parkinson Disease Risk

by Ziv Gan-Or

Objective  To examine whether PARK16, which was recently identified as a protective locus for Parkinson disease... more Objective  To examine whether PARK16, which was recently identified as a protective locus for Parkinson disease (PD) in Asian, white, and South American populations, is also associated with PD in the genetically homogeneous Ashkenazi Jewish population.

Design  Case-control study.

Setting  A medical center affiliated with a university.

Subjects  Five single-nucleotide polymorphisms (SNPs) located between RAB7L1 and SLC41A1 were analyzed in 720 patients with PD and 642 controls, all of Ashkenazi Jewish origin.

Main Outcome Measures  Haplotypes were defined and risk estimates were determined for each SNP and haplotype. Bioinformatic analysis defined the putative promoter region of RAB7L1 and the transcription factor binding sites that are potentially affected by 2 of the tested SNPs.

Results  All tested SNPs were significantly associated with PD (odds ratios = 0.64-0.76; P = .0002-.014). Two of them, rs1572931 and rs823144, were localized to the putative promoter region of RAB7L1 and their sequence variations altered the predicted transcription factor binding sites of CdxA, p300, GATA-1, Sp1, and c-Ets-1. Only 0.4% of patients were homozygous for the protective rs1572931 genotype (T/T), compared with 3.0% among controls (P = 5 x 10–5). This SNP was included in a haplotype that reduced the risk for PD by 10- to 12-fold (P = .002-.01) in all patients with PD and in a subgroup of patients who do not carry the Ashkenazi founder mutations in the GBA or LRRK2 genes.

Conclusions  Our data demonstrate that specific SNP variations and haplotypes in the PARK16 locus are associated with reduced risk for PD in Ashkenazim. Although it is possible that alterations in the putative promoter of RAB7L1 are associated with this effect, the role of other genes in this locus cannot be ruled out

Creating value that changes lives: online communities for the disabled or chronically unwell

by Steven D'Alessandro

A paper on the use of online health forums by the cronically unwell.  Conference paper presented at the ANZMAC conference in 2011.  Co-authored with Susan Stewart Loane as lead author.

People who suffer chronic illness or significant disability often find it difficult to participate in normal... more People who suffer chronic illness or significant disability often find it difficult to participate in normal neighbourhood community life.  Both the sufferer and their carers and family lose contact with neighbours, friends and the workplace and are unable to participate meaningfully.  This study uses qualitative methods to examine online health communities for people suffering from two degenerative neurological diseases, Parkinson’s Disease and Motor Neuron Disease and finds that participants in these online communities are creating peer-to-peer value through social capital exchange and a vibrant exchange of social support.  The study finds that participation in online health communities can provide opportunities to significantly improve the lives of people who are disabled or chronically unwell

Efficient Conversion of Astrocytes to Functional Midbrain Dopaminergic Neurons Using a Single Polycistronic Vector

by Russ Addis

Direct cellular reprogramming is a powerful new tool for regenerative medicine. In efforts to understand and treat... more Direct cellular reprogramming is a powerful new tool for regenerative medicine. In efforts to understand and treat Parkinson's Disease (PD), which is marked by the degeneration of dopaminergic neurons in the midbrain, direct reprogramming provides a valuable new source of these cells. Astrocytes, the most plentiful cells in the central nervous system, are an ideal starting population for the direct generation of dopaminergic neurons. In addition to their potential utility in cell replacement therapies for PD or in modeling the disease in vitro, astrocyte-derived dopaminergic neurons offer the prospect of direct in vivo reprogramming within the brain. As a first step toward this goal, we report the reprogramming of astrocytes to dopaminergic neurons using three transcription factors – ASCL1, LMX1B, and NURR1 – delivered in a single polycistronic lentiviral vector. The process is efficient, with 18.2±1.5% of cells expressing markers of dopaminergic neurons after two weeks. The neurons exhibit expression profiles and electrophysiological characteristics consistent with midbrain dopaminergic neurons, notably including spontaneous pacemaking activity, stimulated release of dopamine, and calcium oscillations. The present study is the first demonstration that a single vector can mediate reprogramming to dopaminergic neurons, and indicates that astrocytes are an ideal starting population for the direct generation of dopaminergic neurons.

Disorders with Synuclein Pathology and Parkinsonism

by Laura Kilarski

published in 'Encyclopedia of Life Sciences', 2009

A variety of neurodegenerative disorders are classified as synucleinopathies based on the presence of prominent... more A variety of neurodegenerative disorders are classified as synucleinopathies based on the presence of prominent α-synuclein pathology. These diseases include Parkinson disease (PD) and dementia with Lewy bodies (with neuronal Lewy body formation) and multiple system atrophy (with glial cytoplasmic inclusions). The normal function of α-synuclein includes regulation of pre-synaptic vesicles. Autosomal dominant PD can be due to coding mutations or multiplications of the α-synuclein gene (SNCA). The coding mutations are thought to lead to a gain of function, in particular acceleration of the formation of proto-fibrils. Duplications and triplications of SNCA lead to autosomal dominant PD with a gene dosage effect on age of onset and clinical severity; variants in the SNCA promoter which lead to an upregulation of SNCA expression are associated with an increased risk of sporadic PD.

Regulation of Synaptic Structure by Ubiquitin C-Terminal Hydrolase L1

by Stevan Djakovic

Caenorhabditis elegans selects distinct crawling and swimming gaits via dopamine and serotonin

by Andrés Vidal-Gadea

PNAS

Many animals, including humans, select alternate forms of motion (gaits) to move efficiently in different... more Many animals, including humans, select alternate forms of motion (gaits) to move efficiently in different environments. However, it is unclear whether primitive animals, such as nematodes, also use this strategy. We used a multifaceted approach to study how the nematode Caenorhabditis elegans freely moves into and out of water. We demonstrate that C. elegans uses biogenic amines to switch between distinct crawling and swimming gaits. Dopamine is necessary and sufficient to initiate and maintain crawling after swimming. Serotonin is necessary and sufficient to transition from crawling to swimming and to inhibit a set of crawl-specific behaviors. Further study of locomotory switching in C. elegans and its dependence on biogenic amines may provide insight into how gait transitions are performed in other animals.

Disturbed dreaming in medical conditions (2004)

by Tore Nielsen

Brain oxidative stress and selective behaviour of aluminium in specific areas of rat brain: potential effects in a 6-OHDA-induced model of Parkinson's disease

by Javier Iglesias-Gonzalez

Sánchez-Iglesias S, Méndez-Alvarez E, Iglesias-González J, Muñoz-Patiño A, Sánchez-Sellero I, Labandeira-García JL, Soto-Otero R.; J Neurochem. 2009 May;109(3):879-88.

The ability of aluminium to affect the oxidant status of specific areas of the brain (cerebellum, ventral midbrain,... more The ability of aluminium to affect the oxidant status of specific areas of the brain (cerebellum, ventral midbrain, cortex, hippocampus, striatum) was investigated in rats intraperitoneally treated with aluminium chloride (10 mg Al3+/kg/day) for 10 days. The potential of aluminium to act as an etiological factor in Parkinson's disease (PD) was assessed by studying its ability to increase oxidative stress in ventral midbrain and striatum and the striatal dopaminergic neurodegeneration induced by 6-hydroxydopamine in an experimental model of PD.The results showed that aluminium caused an increase in oxidative stress (TBARS, protein carbonyl content, and protein thiol content) for most of the brain regions studied, which was accompanied by a decrease in the activity of some antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase). However, studies in vitro confirmed the inability of aluminium to affect the activity of those enzymes. The reported effects exhibited a regional-selective behaviour for all the cerebral structures studied. Aluminium also enhanced the ability of 6-hydroxydopamine to cause oxidative stress and neurodegeneration in the dopaminergic system, which confirms its potential as a risk factor in the development of PD.