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Age and Ageing 2013; 42: 2–10 © The Author 2012.

Published by Oxford University Press on behalf of the British Geriatrics Society.
doi: 10.1093/ageing/afs103 All rights reserved. For Permissions, please email:
Published electronically 19 August 2012


New horizons in the pathogenesis,
assessment and management of movement

Institute of Ageing and Health, Newcastle University, Newcastle upon Tyne NE4 5PL, UK
Address correspondence to: G. W. Duncan. Tel: (+44) 191 248 1241; Fax: (+44) 191 248 1251. Email: gordon.duncan@

In this review, we shall outline recent advances in our understanding of the movement disorders which geriatricians encounter in
their clinical practice. Many of these diseases are no longer simply considered disorders of movement: carefully conducted longitu-
dinal studies have shown that concomitant cognitive dysfunction, neuropsychiatric disturbance and behavioural issues are frequent
and exert a heavy burden on the individual and their carers. Great progress has been made in understanding the molecular and cel-
lular processes that drive the pathological changes in these conditions, as have advances in neuroimaging and preclinical drug dis-
covery programmes. Unfortunately, this is yet to translate into disease-modifying therapies for these progressive disorders.
Advances have been also made in non-pharmacological interventions such as tailored physiotherapy and speech therapy pro-
grammes. The important contribution of palliative care has been recognised and increasingly incorporated into the multidisciplin-
ary approach. The UK is at the forefront of research into these conditions and geriatricians are well placed to contribute to
research through recruiting patients to observational studies or therapeutic trials, particularly with the support of agencies such as
the National Institute for Health Research—Dementias & Neurodegenerative Diseases Research Network (NIHR-DeNDRoN).

Keywords: movement disorders, Parkinson’s disease, progressive supranuclear palsy, dementia with Lewy bodies, multiple
system atrophy

Introduction abnormal protein handling and oxidative stress with subse-
quent cell toxicity and death. Parkinson’s disease (PD), de-
In this ‘New Horizons’ article, we will focus on the move- mentia with Lewy bodies (DLB) and multiple system atrophy
ment disorders which geriatricians encounter in routine clin- (MSA) are synucleinopathies, whereas progressive supra-
ical practice. We will outline recent advances in the clinic and nuclear palsy (PSP), corticobasal degeneration (CBD) and
laboratory and how these are translating into better under- some forms of frontotemporal lobe degeneration are driven
standing of the pathological processes driving these condi- by tau pathology. The clinical features are the manifestation
tions, improved diagnostic accuracy and, ultimately, paving of degeneration in select neuronal populations influenced by
the way for the development of disease-modifying therapies. the distribution of pathology, the proteinopathy driving the
disease and any co-existent pathological processes.
Degenerative movement disorders
No longer considered purely disorders of movement, Synucleinopathies
many patients will have co-existent cognitive impairments
and neuropsychiatric disturbances which are equally trouble- Parkinson’s disease
some for them and their carers. These degenerative protei- PD is the second most common neurodegenerative dis-
nopathies, which are outlined in Table 1, are characterised by order after Alzheimer’s disease [1]. The pathological hallmark


autonomic dysfunction and dementia neuropsychiatric disturbances... have been linked to PD and require further evaluation.. Four distinct parkinsonism onset clinical phenotypes have been described and are outlined in Multiple system MSA-Cerebellar variant Table 1..... degeneration PSP-like syndrome Non-motor symptoms (NMS) are important predictors Progressive non-fluent aphasia Behavioural variant frontotemporal of the quality of life [12] and approximately half of NMS degeneration are not reported or recorded [13]. the ultimate all cases.. these patients are often older and have more Corticobasal Corticobasal syndrome extensive cortical LB deposition [10].. Animal and Guideline on PD [15]. Classification of degenerative movement disorders 2500 patients with new and young-onset PD to further according to protein aggregation define the importance of genetic factors in the development and progression of PD.. offering further tion. and the substantia nigra pars compacta. Recent research has focused Dementia with Dementia precedes parkinsonism or on motor phenotype classification and its correlation with Lewy bodies occurs within one year of pathology and patterns of disease progression.. Cognitive.. perceptual. however. Each is associated with a different disease trajec- atrophy MSA-Parkinsonian variant tory: those with younger onset or tremor-dominant presen- Pure Autonomic Failure tations appear to have a longer time interval to developing Tauopathy Progressive PSP-Richardson syndrome falls and dementia [10].. The pattern of cognitive deficits in tures. with visual hallucinations. A recent incidence study highlights that those with very early PD experienced a greater number of of PD is degeneration of the dopaminergic neurons within NMS when compared with age-matched controls. Progressive non-fluent aphasia autonomic. sleep and sexual symptoms occurred in over 30% of patients. Constipation and The incidence of PD increases with age [1]. or rostral spread.. Many NMS predate the onset of cellular models have confirmed that mitochondrial dysfunc. monogenetic forms predominate in those with goal being to identify those at highest risk of developing young-onset PD and at least eight loci of importance have PD and allowing the rational targeting of future disease- been identified with Genome Wide Association Studies [5]. Some mutations are associated with certain clinical fea.. [14] reported noc- Semantic dementia turia to be the most prevalent NMS. modifying strategies.. possibly suggesting an intestinal route of remains unclear [3].. Patients with postural instability and supranuclear PSP-Parkinsonism gait difficulty typically develop falls and dementia sooner palsy Pure akinesia with gait freezing [11]. For research 3 . progression [4].... cognitive fluctuations and The UK-wide ‘Tracking Parkinson’s’ Study aims to recruit visuospatial dysfunction being core features. submitted)... a positive family history may be an important risk factor and mutations in the leucine-rich repeat kinase 2 gene (designated PARK 8) are Cognitive and neuropsychiatric issues found in 1–2% of European patients with idiopathic PD Dementia may ultimately develop in almost 80% of those [6]. New Horizons in the pathogenesis Table 1.. Accounting for only a small proportion of which is currently the subject of intense study. entry with centripetal.’ LBs have been found in the colonic mucosa pathology is directly cytotoxic or represents a failed response of those with PD up to 5 years prior to the onset of motor by the cell to confine and eliminate cytotoxic proteins parkinsonism [17]... AD. Synucleinopathy Parkinson’s Early or young-onset disease Tremor-dominant Non-tremor dominant/ Clinical advances Postural-instability and gait difficulty The clinical features of PD encompass motor abnormal- Rapid disease progression without ities.. Driven by the deposition those with the postural instability gait disorder subtype of of insoluble phosphorylated α-synuclein-containing inclu. or dominant disease (Khoo et al. abnormal protein aggregation and oxidative stress are insight into the development of PD and suggesting a ‘pre- implicated in the pathogenesis of PD. mood and olfaction are common and older age at onset is strongly associated with faster disease collectively may represent a Parkinson at Risk Syndrome.... but whether Lewy motor phase.. cognitive impairments. Martinez-Martin et al.. the H1 haplotype of the microtubule-associated Parkinson's disease dementia (PDD) is very different from protein tau gene confers an increased risk of dementia [7]... The importance axons as Lewy neurites.... with PD [18]. Using the 30-point NMS screening questionnaire (NMSQuest) in 545 patients across Pick’s disease Behavioural variant frontotemporal degeneration all stages of PD. and an disturbances of sleep. motor dysfunction by many years [16].. these lesions are found throughout of recognising and managing NMS is emphasised in the the central and autonomic nervous systems and become National Institute for Health and Clinical Excellence more widespread with disease progression [2]. Environmental factors such as sol- Disease Phenotypic variants and clinical vents containing trichloroethylene [8] and pesticides [9] presentations ... Within the general population.. the disease had a higher burden than those with tremor- sions within the neuronal cytoplasm as Lewy bodies.

freezing and falls. A recent Cochrane Review supports the use of cholinesterase inhibitors. Subtle cognitive dysfunction or mild cognitive impair. not only the dopaminergic deficits. attention and DBS of the subthalamic nucleus (STN) is an established executive impairments are most commonly observed.G. the quality of life for the individual and their carer. further information from large observational excludes a significant proportion of the population seen by studies is needed to inform the prognostic significance of geriatricians. Dementia with Lewy bodies Predominately associated with DA use. visual hallucinations and parkinsonism 4 . quently than multiple domain impairments. The evidence base for treatment is ganglia and cortex [34] and may play an important role in limited. for this to randomised controlled trial (RCT) of venlafaxine and par. underway in the UK and Holland. with 3. behavioural symptoms and activities of daily living sparse.7%). gestive of an ICD should be enquired about regularly. In a cross-sectional study of over 3. major depression is reported in found degeneration in PD. DLB is differentiated from PDD by deep brain stimulation (DBS) [32]. de. but also the other neuro- ment will begin shortly. but not the overall UPDRS score. which may be beneficial in im- by gambling (5. posture and gait. stages and experienced physiotherapists are essential [39]. velopment of an ICD include male sex. and almost 50 years after their introduction. binge-eating (4. Non-drug treatments suitable for this population. In general. not normal for age. followed the role of physiotherapy. Disease-modifying drugs that slow the rate a cognitive decline which. There is a need for better treatments to address the effects of the early institution of donepezil and recruit. Input from PD specialist Impulse control disorders (ICDs) in those receiving nurses improves patients’ sense of well-being at no add- dopamine agonists (DAs) are an increasingly recognised itional cost [37]. A recent double-blind RCT [35] of unilat- Selective serotonin reuptake inhibitors are commonly pre. Table 2 shows some ment (MCI) occurs in around a quarter of patients and is of the drugs currently being trialled for PD in Europe and reported across all stages of PD [22]. serotonergic and noradrenergic systems. Speech and language therapy in the assess- phenomenon. although it should be noted that this study consisted of subjects aged under 75.000 ment and management of dysphagia is well-established. for patients with PD [30]. be achieved. ICDs were more frequent in that different strategies are required for different disease those prescribed a DA compared with other anti. or occur history of gambling or depression. PD-MCI is defined as North America. sought prior to the initiation of DAs and behaviours sug- ifestations of PD. The anti-depressant properties Trials of multidisciplinary rehabilitation and exercise are of pramipexole have recently been recognised [29]. Duncan et al.0%). Evidence is growing for Compulsive shopping was most prevalent (5. In contrast to the motor man. STN stimulation has little impact upon gait PD-MCI. and there- fore the applicability to older patients may be limited. Treatment may be beneficial [38]. 24]. is of dopaminergic nigral degeneration would simplify the man- still associated with essentially normal functional activities agement of motor problems. in surgical option [33]. which unfortunately however. even greater than that seen in AD [20]. There mic region may be required [36]. transmitter derangements that occur within the cholinergic. parkinsonian medications. Key to its success is careful lead place- contrast to the general ageing population where amnestic ment and patient selection: Patients should be under 70 deficits predominate [22]. mentia is underpinned by a profound cholinergic deficiency. younger age and a tive dysfunction to precede motor symptoms. Risk factors for the de- the ‘1-year rule’ [19]: the diagnosis of DLB requires cogni. dysfunction. but their anti-cholinergic properties often make them un. and these should be within 1year of motor onset. 13. eral PPN stimulation demonstrated benefit in terms of re- scribed and a recent placebo-controlled double-blind ducing falls. psychiatric or cognitive disturbance. with New treatments for PD rivastigmine having modest benefits in global function. and clinical purposes. the drug development pipeline for PD is relatively nition. the preparations remain the most effective form of oral therapy. but it is important to note sexual behaviours (3. cog.3%) and compulsive proving gait. with trials often small and of short duration.9% having two or more ICDs. ICDs have been Dementia with Lewy bodies is characterised by fluctuating im- reported in patients receiving levodopa [31] and following pairment of cognition. Undergoing pro- Across all stages of PD. bilateral stimulation of the PPN and subthala- oxetine supported the use of both over placebo [26]. 28]. although. with a further 1–30% suffering minor (PPN) provides significant cholinergic input to the basal depressive episodes [25].5%). likewise slowing the onset of de- [22] and guidance for formal neuropsychological testing is mentia and non-motor features would significantly enhance available [23]. W. Two longitudinal studies reported with L-dopa responsive disease and no significant neuro- increased dementia risk in those with PD-MCI [7. Health Technology Assessment programme funded Stem cell and gene transfer strategies have thus far proved dis- UK-based multi-centre MUSTARDD-PD trial will evaluate appointing. is some evidence supporting tricyclic anti-depressants such as nortriptyline and desipramine in PD depression [27. which reflect dopaminergic deficiency. Single domain impairments occur more fre. the pedunculopontine nucleus 5–20% of patients.6% of patients were identified as quiet speech and dysphonia the Lee Silverman Voice having an ICD. axial symptoms and falls. For those with early PDD. L-dopa in those with PDD [21].

... Disease-modifying Creatine Supports mitochondrial function NET-PD III Measures of disease progression over 5 NCT00449865 years Due to report in May 2015 Inosine Higher serum urate levels are associated SURE-PD II Safety and tolerability study with slower progression of PD........... sodium channel antagonist and NCT01028586 safinamide delays the need to initiation glutamate release inhibitor of dopaminergic therapy in early PD patients Preladenant Adenosine A2 receptor antagonist NCT01155479 III Safety and tolerability study Change from baseline in UPDRS Advanced PD AFQ-056 Metabotropic glutamate receptor 5 NCT01491932 II Open label extension phase antagonist (immediate release) Double blind-phase showed significant benefit in the primary outcome AIMS scores AFQ-056 Metabotropic glutamate receptor 5 NCT01491529 II Safety and efficacy study antagonist (modified release) Change from the baseline in the dyskinesia score in those with dyskinesia IPX066 Extended-release oral formulation of ADVANCE-PD III Open label extension phase recording carbidopa and levodopa changes in UPDRS and motor fluctuations based on home diaries..... Safety and tolerability measures also Continued 5 ..............1 h improvement in ON time without troublesome dyskinesia compared with immediate release levodopa BIA9-1067 Long-acting COMT inhibitor BIPARK2 III Aims to show reduced OFF time NCT01568073 compared with entacapone or placebo Preladenant Adenosine A2 receptor antagonist NCT01155466 III Mean reduction in OFF time Safinamide MAOB inhibitor...005)............. Inosine NCT00833690 Will measure CSF urate levels in patients is an urate precursor that raises urate with early PD levels in blood and CSF Israpadine CR Calcium antagonist STEADY-PD II Safety and tolerability study NCT00909545 UPDRS measure of disease progression N-acetylcysteine Reduces oxidative stress as a free radical NCT01470027 II Measures of glutathione activity and scavenger clinical measures Deferiprone An iron chelator that has been shown to NCT01539837 II Safety and tolerability study reduce iron deposition in Friedreich MRI measures of SN iron accumulation ataxia patients. Summary of clinical trials currently testing new drugs for Parkinson’s disease in Europe and North America Drug Action Trial name Phase Comments .... New Horizons in the pathogenesis Table 2.........63 h (P = 0.. Excess iron deposition is implicated in SN toxicity Pioglitazone PPAR-gamma agonist that slows disease NCT01280123 II Patients with early PD being recruited to progression in rats and increases striatal this safety and tolerability study dopamine levels AAV2-Neururin Neurotrophic growth factor that is directly NCT00985517 I/II Change from baseline UPDRS III in OFF (CERE-120) injected into the SN and putamen state Cogane Oral neurotrophic factor modulator NCT01060878 II Change from baseline in UPDRS II and (PYM-50028) III in those with early and untreated PD Early Motor IPX066 Extended-release oral formulation of NCT01096186 III Open label extension..008).... dopamine reuptake MOTION III Extension study measuring whether inhibitor...... 100 mg versus placebo 0..... dopamine reuptake SETTLE III Some increase in ON time increase at 24 inhibitor...... to APEX-PD carbidopa and levodopa which showed modest improvement in UPDRS in those with early PD Side-effects included nausea and vomiting Safinamide MAOB inhibitor..... sodium channel antagonist and NCT00627640 weeks: 50 mg versus placebo 0.. Earlier phase showed 1..59 h (P glutamate release inhibitor = 0....

.... 60% had >30% reduction in mean daily OFF time..... poorly levodopa-responsive par- helpful [41]. the latter occurring more often in DLB than Multiple system atrophy PDD..... mood and cognitive with inherited spinocerebellar ataxia tests Non-motor Droxidopa Noradrenaline precursor for neurogenic NCT01176240 III Mean change in the Orthostatic orthostatic hypotension Hypotension Questionnaire composite score Lubiprostone Prostaglandin E1 derivative for NCT00849784 IV Measures of change in bowel movement constipation frequency Solifenacin Muscarinic receptor antagonist URGE-PD IV Reduction in daily number of micturitions NCT01018264 Neuropsychiatric Pimavanserin 5HT2A receptor antagonist NCT01518309 III Safety and efficacy studies for the NCT00550238 treatment of PD psychosis.. Symptomatic treatment remains limited to rivas... which improves both cognition is the presence of α-synuclein containing glial cytoplasmic 6 .. there is extensive cortical and neocor..... High NCT01174004 placebo response with no benefit of pimavanserin... Table 2..... improvement will be measured by the global impression of change Dementia Rivastigmine Acetylcholinesterase inhibitor NCT01519271 IV Due to report in 2014 Recruiting patients with mild cognitive impairment Donepezil Acetylcholinesterase inhibitor MUSTARDD-PD III Twenty-two sites across UK aim to recruit NCT01014858 500 patients with early PD dementia [19]... Allows more time for L-dopa concentrations than IR transport across the GI tract carbidopa and levodopa.... Trends towards improvement of psychosis without impairing mobility Naltrexone Long-acting opioid receptor antagonist NCT01052831 IV For those with ICDs due to DA therapy..... Improved Chantix-PD II Change in Berg Balance scale...... Differentiation from AD in its early stages can be MSA manifests as severe autonomic dysfunction with cere- challenging and 123I-FP-CIT SPECT imaging may be bellar features (MSA-C).. imbalance in initial studies in patients NCT01341080 MDS-UPDRS.......... and behavioural features [43].... neurofibrillary tangles and deposition of β-amyloid........ Most recently memantine has tical LB deposition which correlates with the severity of been shown to improve some neuropsychiatric features [44]... XP-21279 Sustained-release formulation levodopa NCT01171313 II Earlier study showed less variability in pro-drug. Mean time to ON after 1st morning dose was similar SYN115 Adenosine A2 receptor antagonist NCT01283594 II/III Change from the baseline in mean OFF time without troublesome dyskinesia Nicotine Transdermal nicotine NICOPARK2 II Measuring change in UPDRS in the OFF NCT00873392 state Due to report in 2014 AAV-hAADC-2 Gene coding for the enzyme that converts NCT00229736 II Safety study in those with mid-to-late L-dopa to dopamine (AADC) is inserted stage PD into a non-pathogenic virus and injected into the striatum ProSavin Intraputaminal injection of enzymes NCT00627588 I/II Safety and tolerability study required for dopamine synthesis Gait and balance Rivastigmine Acetylcholinesterase inhibitor ReSPonD II Recruiting patients with PD who have ISRCTN19880883 fallen Will measure gait variability and other tasks Donepezil Acetylcholinesterase inhibitor NCT01521117 IV Measuring changes in balance and walking Varenicline Nicotinic receptor agonist....... Duncan et al. cognitive decline [40] as well as basal forebrain cholinergic neuronal loss...G.. Continued Drug Action Trial name Phase Comments ...... The pathological hallmark tigmine [42] or donepezil.. W. kinsonism (MSA-P) or both [45]....... Pathologically.

57]. Current treatment strategies are fluency. including lithium and Tideglusib have been disappoint- Riluzole. which aim to reduce tau de- most cases are sporadic. a range of different pathologies including tau. features encompass chorea. versely with the number of trinucleotide repeats. drugs.6% in those over 65-year-old [61]. A further approach is to stabilise the neuronal cytoskel- (MND). A have shown early promise in mice models include erythro. a PSP variant designated American and European studies are ongoing in the search PSP-Parkinson (PSP-P) has been described with clinical fea. Potential disease-modifying therapies that promise in a phase II trial and a further trial is ongoing. early falls (often sion in the Huntington gene on chromosome 4 [59] with backwards) and supranuclear vertical gaze palsy or slowing severe neuronal loss in the putamen and caudate. tigmine may improve neuropsychiatric features but with no impact upon cognition [58]. Q-10. or with a more PSP-like variant with the CNS. rising to 4. North mean of 7 years. A trial of rasagiline in patients with Therapeutics) and trials are underway at present. gabapentin [55] No longer labelled as ‘benign. dystonia. as are searches for neuroprotective treatments including co- tions. dystonia. which supports mitochondrial function. phenotypic descriptor which may be the manifestation of normally insoluble tau forms fibrillar structures of aggregated. showed onstrate efficacy. Other features include frontalis muscle hyper. pallidum. unilateral limb apraxia. Trials of striatal foetal implants are underway. Studies of cholinesterase inhibitors [54]. thalamus and STN [51]. Progressive supranuclear palsy Progressive supranuclear palsy is the most common tauopa. CBS is a clinical protein found within the neuron: in the disease state the ab.4–0. Treatment is supportive. To date. The of saccades. polymorphisms in the SNCA gene position via inhibition of tau hyperphosphorylation and ag- have been identified. DBS has been used for disabling chorea in PSP is relentlessly progressive. unsatisfactory and include the use of antidepressants and nise emotions [52]. New Horizons in the pathogenesis inclusions in the central nervous system (CNS) [46].9% across all ing is another uncommon phenotypic variant of PSP. these patients may respond to L-dopa Essential tremor and the mean survival is longer. which prolongs survival in motor neuron disease ing. and has a Tauopathies variety of presentations. enzyme Q10. motor and 7 . the later reduces α-synuclein fibril formation and a human trial is underway. did not improve survival in MSA patients in the eton through enhancing the synthesis of Activity-Dependent Neuroprotection and Natural History in Parkinson Plus Neuroprotective Protein with nasal davenutide (Allon Syndromes study [48]. inflexibility of thought and impaired ability to recog. no treatments have been shown tau hyperphosphorylation. tau is a soluble microtubule-associated aphasia or behavioural change [56. Disease-modifying and may be associated with neuropsychiatric. Corticobasal degeneration Diagnosis of CBD is challenging: it is rare. rivas- MND-like appearance [51]. phase III trial of rasagiline is currently recruiting participants. but trials of GSK-3-inhibiting to slow the disease progression or improve survival. Other movement disorders thy and is characterised by abnormal deposition of four- repeat tau fibrillary tangles in neurons and glial cells within Huntington’s disease (HD) is an autosomal dominant the midbrain. Alzheimer’s hyperphosphorylated and ubiquinated tau with subsequent disease pathology. atric and metabolic disturbances and may develop between Early impairments of cognition manifest as reduced verbal the ages of 1 and 80 years. Neuropsychiatric disturbances such as apathy.’ the tremor often progresses and riluzole [48] have been disappointing. Glycogen synthase kinase-3 (GSK-3) is critical for pathogenesis [47]. disease shows anticipation and the age of onset correlates in- activity giving the patient a startled expression. More recently. The clinical pened voice. While strategies are being developed. adding to our understanding of the gregation. and a dee. It may present with the classical features of corticobasal syndrome (CBS) including limb Tauopathies are characterised by the accumulation of hyper. Dementia is almost universal with disease antipsychotics. for reliable biomarkers for those with pre-manifest HD. tures similar to PD: gaze palsy is less prominent. cognitive. autonomic dysfunction and sleep disturbance are rare. In contrast to the synucleinopathies. LBs or frontotemporal lobar degener- cellular toxicity. action myoclonus or cor- phosphorylated tau protein within neurons and glial cells in tical sensory loss. age groups. with death occurring after a younger patients but experience is limited [60]. Normally. Coenzyme MSA-P is due to fully report later in 2012 but did not dem. Pathological four-repeat tau accumulation is syndromes with varying degrees of parkinsonism and common to the CBD and PSP and may be present in up dementia—particularly with frontal lobe involvement or an to half of cases of CBS [57]. poietin [49] and rifampicin [50]. neuropsychi- change in social behaviour and aggression are prominent. Pure akinesia with gait freez. progression. bradykinesia. hallucina. rigidity and tremor are more unilateral and cognition is pre- served for longer [53]. Essential tremor has a prevalence of 0. The result is a range of heterogeneous clinical ation [57]. and L-dopa is not helpful. The classic progressive neurodegenerative disease caused by a Steele-Richardson syndrome typically presents in patients cytosine-adenine-guanine (CAG) trinucleotide repeat expan- over 40 years of age with akinetic rigidity.

disease award to the Newcastle upon Tyne Hospitals NHS isfactory. Common issues include pre- Pathologically. received educational grants from UCB and Abbott for ition to providing education and support for patients and attending conferences. care physicians are increasingly involved in the care of position has being reported in some studies also [63]. antibiotic use for pulmonary infections particularly those expressing GABAA and GABAB receptors and the use or withdrawal of artificial nutrition. but botulinum toxin injection to focal muscle Foundation Trust. patients with advanced PD and other neurodegenerative dis- Propanonlol is established as the first-line therapy. Rub U et al. He has received hon- therapy. This work was also supported by the UK NIHR may be focal and may display a geste antagoniste (sensory trick Biomedical Research Centre for Ageing and Age-related that reduces tremor) [66]. possibly due Capacity Act 2005 [67] and discussions regarding ACP can to considerable heterogeneity within the patient population be tailored to the patient and their family with regard to and confounding factors such as age and co-morbid disease. no convincing advance care planning (ACP) was provided by the Mental loci have been identified despite exhaustive study. Conflicts of interest Horizon scanning None declared. W. Cell Tissue disease-modifying treatments make the requirement for a Res 2004. without evidence of dopaminergic deficit’ (SWEDDS). Ghebremedhin E. D. but up to eases. University Lockhart Parkinson's Disease Fund. blood and cerebrospinal and acted as consultant for GSK and Archimedes. Palliative in the dentate nucleus of the cerebellum. has received grants from which not only permit earlier diagnosis. Stages in the devel- movement disorders. the topic-specific NIHR-Dementias & Neurodegenerative Diseases Research Network (NIHR. N Engl J Med 2003. Braak H. MJ Fox Foundation. Tremendous advances have been made in the characterisa- tion of the clinical features and underlying cellular mechan- Dystonic tremor isms that underpin the movement disorders seen in older This diagnosis has emerged with the increased use of dopa. The relentless progression of most neurodegenerative 2. groups has been tried with some success. GSK and disease progression and which may be used for drug dis.W. Success in developing disease-modifying treatments the Newcastle University Lockhart Parkinson’s Disease will require the following: a better understanding of the Fund and MJ Fox Foundation. fluid markers. functional co-morbidities [62]. from Teva-Lundbeck and UCB for attending conferences the development of animal models that accurately reflect S. Available oral treatments are unsat. Refractory cases may be considered for DBS of the ventralis intermedius nucleus of Conclusion the thalamus. She has received funds from UCB covery programmes. brain stem LB de. Labelled as ‘scans patients and are currently the focus of intense research efforts. is supported by grants from carers. These advances have yet to translate into disease- mine imaging in therapeutic trials where a misdiagnosis rate of modifying therapies. The legal framework for dominant manner with reduced penetrance. Funding Within England. ferred place of care. people. mate are the second-line and may work via gamma-aminobu- tyric acid receptor activation. many of these patients demonstrated mild dystonic posturing and Acknowledgements were thus considered to have dystonic tremor. and Michael J Fox Foundation. is supported by a grant from the Newcastle DeNDRoN) has a role in facilitating projects studying PD. Inherited in an autosomal palliative approach essential. Parkinson’s disease progression and response to disease-modifying UK.Y. Such biomarkers are likely to be drawn from a oraria from Teva-Lundbeck and UCB in the past two years multimodal panel of neuroimaging. A. The UK is at the forefront of movement disorder research and geriatricians are well placed to participate in this. He has Parkinson’s UK is a major funder of PD research in add. unfortunately those with advanced PD are currently half of patients fail to respond [64]. 318: 121–34. References Advance care planning and palliative care 1. there may be a loss of cerebellar Purkinje cells.M. 348: 1356–64.J. Ellis CE. and the validation of biomarkers for attending conferences. G. GlaxoSmithKline Ltd. Gabapentin and topira. more likely to die in hospital than in a hospice or at home. Alzheimer’s disease and Parkinson’s disease. often with good results.J. their disease type and stage. 8 . but also measure NIHR.B. Nussbaum RL. The tremor is usually an atypical jerky rest tremor that is generally unilateral.G. is funded by grants from Parkinson’s UK.D. Wellcome Trust. which will revolutionise the care these up to 15% was noted after imaging [65]. high symptom burden and paucity of opment of Parkinson’s disease-related pathology. She has received funds mechanisms that underlie neuronal cell toxicity and death. Duncan et al.

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