ORCID Profile
0000-0002-5456-8676
Current Organisations
University of Tasmania
,
University of Leeds
,
Royal Hobart Hospital
,
Leeds Teaching Hospitals NHS Trust
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Publisher: Wiley
Date: 18-10-2016
DOI: 10.1002/MDS.26805
Abstract: Mind-brain dualism has dominated historical commentary on dystonia, a dichotomous approach that has left our conceptual grasp of it stubbornly incomplete. This is particularly true of functional dystonia, most diagnostically challenging of all functional movement disorders, in which the question of inherent psychogenicity remains a focus of debate. Phenomenological signs considered in isolation lack the specificity to distinguish organic and nonorganic forms, and dystonia's variability has frustrated attempts to develop objective laboratory-supported standards. Diagnostic criteria for functional dystonia that place emphasis on psychiatric symptoms perform poorly in studies of reliability, partly explained by the high frequency of psychopathology in organic dystonia. Novel approaches from the cognitive neurosciences may offer a way forward. Theory on Bayesian statistical prediction in cognitive processing is supported by sufficient experimental evidence for this model to be taken seriously as a way of reconciling contradictory notions about voluntary and unconscious motor control in functional movement disorders. In a Bayesian formulation of functional dystonia, misallocation of attention and abnormal predictive beliefs generate movements that are executed without a sense of agency. Building on this framework, there is a consensus that a biopsychosocial approach is required and that a unified philosophy of brain and mind is the best way to locate dystonia in the neurology-psychiatry borderland. At a practical level, movement disorder neurologists are best placed to differentiate organic from functional dystonia. The main role of psychiatrists is in the diagnosis and management of the primarily psychiatric disorders that often accompany dystonia. © 2016 International Parkinson and Movement Disorder Society.
Publisher: BMJ
Date: 26-08-2017
Publisher: Oxford University Press (OUP)
Date: 20-06-2011
Abstract: Tremor is, by definition, a rhythmic oscillation of a body part. It is the most prevalent movement disorder in clinical medicine, so doctors working in many specialities and in general practice can expect to encounter it. Most tremors can be classified on the basis of four observable clinical characteristics: anatomical pattern the relative prominence of the tremor at rest, on maintaining a posture, and with action tremor frequency and tremor litude. A resting tremor suggests Parkinson’s disease, and the diagnosis then depends on a judgement about whether the patient has other signs of parkinsonism. The most common causes of postural tremor are physiological tremor, essential tremor and drug-induced tremor. The differential diagnosis may also include dystonic tremor and psychogenic tremor, while metabolic tremor caused by thyrotoxicosis should be considered in any recent-onset postural tremor. Wilson’s disease and fragile X-associated tremor/ataxia syndrome are rarer conditions that may present with tremor and are very important to identify. There is a small but genuine diagnostic grey zone between Parkinson’s disease and more benign tremor disorders such as essential tremor and dystonic tremor, in which resting and postural tremor coexist with mild or equivocal non-tremor parkinsonian signs. The authors review clinical features and investigational techniques that may help to discriminate this group of hard-to-classify tremors.
Publisher: JMIR Publications Inc.
Date: 03-2022
DOI: 10.2196/34688
Abstract: Up to 40% of incident dementia is considered attributable to behavioral and lifestyle factors. Given the current lack of medical treatments and the projected increase in dementia prevalence, a focus on prevention through risk reduction is needed. We aim to increase dementia risk knowledge and promote changes in dementia risk behaviors at in idual and population levels. The Island Study Linking Aging and Neurodegenerative Disease (ISLAND) is a long-term prospective, web-based cohort study with nested interventions that will be conducted over a 10-year period. Target participants (n=10,000) reside in Tasmania and are aged 50 years or over. Survey data on knowledge, attitudes, and behaviors related to modifiable dementia risk factors will be collected annually. After each survey wave, participants will be provided with a personalized dementia risk profile containing guidelines for reducing risk across 9 behavioral and lifestyle domains and with opportunities to engage in educational and behavioral interventions targeting risk reduction. Survey data will be modeled longitudinally with intervention engagement indices, cognitive function indices, and blood-based biomarkers, to measure change in risk over time. In the initial 12 months (October 2019 to October 2020), 6410 participants have provided baseline data. The study is ongoing. Recruitment targets are feasible and efforts are ongoing to achieve a representative s le. Findings will inform future public health dementia risk reduction initiatives by showing whether, when, and how dementia risk can be lowered through educational and behavioral interventions, delivered in an uncontrolled real-world context. DERR1-10.2196/34688
Publisher: SERDI
Date: 2023
Publisher: Wiley
Date: 30-07-2023
DOI: 10.1002/ALZ.13401
Abstract: Finding low‐cost methods to detect early‐stage Alzheimer's disease (AD) is a research priority for neuroprotective drug development. Presymptomatic Alzheimer's is associated with gait impairment but hand motor tests, which are more accessible, have hardly been investigated. This study evaluated how home‐based Tasmanian (TAS) Test keyboard tapping tests predict episodic memory performance. 1169 community participants (65.8 ± 7.4 years old 73% female) without cognitive symptoms completed online single‐key and alternate‐key tapping tests and episodic memory, working memory, and executive function cognitive tests. All single‐key ( R 2 adj = 8.8%, ΔAIC = 5.2) and alternate‐key ( R 2 adj = 9.1%, ΔAIC = 8.8) motor features predicted episodic memory performance relative to demographic and mood confounders only ( R 2 adj = 8.1%). No tapping features improved estimation of working memory. Brief self‐administered online hand movement tests predict asymptomatic episodic memory impairment. This provides a potential low‐cost home‐based method for stratification of enriched cohorts. We devised two brief online keyboard tapping tests to assess hand motor function. 1169 cognitively asymptomatic adults completed motor‐ and cognitive tests online. Impaired hand motor function predicted reduced episodic memory performance. This brief self‐administered test may aid stratification of community cohorts.
Publisher: ACM
Date: 12-07-2014
Publisher: SAGE Publications
Date: 09-07-2013
Abstract: Parkinson’s disease is a common, life-limiting, neurodegenerative condition. Despite calls for improved access to palliative care for people with Parkinson’s disease, services have been slow in developing. Obstacles include poor understanding and recognition of palliative care needs, the role for specialist palliative care services and an agreed structure for sustainable palliative care provision. To summarise the evidence base for palliative care in Parkinson’s disease, linking current understanding with implications for clinical practice and identifying areas for future research. Convention recognises a final ‘palliative phase’ in Parkinson’s disease, while qualitative studies suggest the presence of palliative care need in Parkinson’s disease from diagnosis. Clinical tools to quantify palliative symptom burden exist and have helped to identify targets for intervention. Dementia is highly prevalent and influences many aspects of palliative care in Parkinson’s disease, with particular implications for end-of-life care and advance care planning. The ‘palliative phase’ represents a poor entry point for consideration of palliative care need in Parkinson’s disease. An alternative, integrated model of care, promoting collaboration between specialist palliative and neurological services, is discussed, along with some specific palliative interventions. Limited evidence exists regarding timing of palliative interventions, triggers for specialist referral and management of terminal care. Research examining access to palliative care and management of terminal symptoms will assist development of sustainable, integrated palliative care services for Parkinson’s disease.
Publisher: Wiley
Date: 13-02-2016
DOI: 10.1002/MDS.26497
Publisher: Elsevier BV
Date: 08-2016
Publisher: Elsevier BV
Date: 11-2020
Publisher: BMJ
Date: 14-02-2019
DOI: 10.1136/JNNP-2019-ABN.130
Abstract: The geste antagoniste is a typical feature of dystonia’s motor phenomenology. Gestes may also occur in functional dystonia. We investigated how gestes affect the kinematics of voluntary movement. Cross-sectional study. Twenty-three patients with organic dystonia and three with functional dystonia were studied. Finger tapping was assessed while subjects wore electromagnetic sensors secured to index finger and thumb. Subjects were instructed to tap ‘as fast and as big as possible’ for 15 s, first with and then without activation of their geste. Precise position and orientation data, in six degrees of freedom, were recorded. Separable motor components were derived from a comparison of the x, y and z coordinates of each sensor. The product of litude and frequency, giving the sensor excursion per unit time, was used as a measure of average speed. A repeated measures ANOVA was conducted, with the factors CONDITION (with vs without geste), HAND (dominant vs non-dominant) and GROUP (organic vs functional). For average speed, there was a significant effect of CONDITION—patients with both organic and functional dystonia performed better with geste (F1,24=13.5 p=0.001). There was no main effect of HAND or GROUP. Geste antagonistes enhance motor performance in organic and functional dystonia. These selective voluntary movements may have a general effect on the execution of motor plans in dystonia. S le numbers were too small to allow meaningful analysis of GROUP effects.
Publisher: Elsevier BV
Date: 06-2020
Publisher: BMJ
Date: 09-02-2012
Publisher: Springer Science and Business Media LLC
Date: 22-07-2023
DOI: 10.1007/S13755-023-00231-0
Abstract: With ageing populations around the world, there is a rapid rise in the number of people with Alzheimer’s disease (AD) and Parkinson’s disease (PD), the two most common types of neurodegenerative disorders. There is an urgent need to find new ways of aiding early diagnosis of these conditions. Multimodal learning of clinically accessible data is a relatively new approach that holds great potential to support early precise diagnosis. This scoping review follows the PRSIMA guidelines and we analysed 46 papers, comprising 11,750 participants, 3569 with AD, 978 with PD, and 2482 healthy controls the recency of this topic was highlighted by nearly all papers being published in the last 5 years. It highlights the effectiveness of combining different types of data, such as brain scans, cognitive scores, speech and language, gait, hand and eye movements, and genetic assessments for the early detection of AD and PD. The review also outlines the AI methods and the model used in each study, which includes feature extraction, feature selection, feature fusion, and using multi-source discriminative features for classification. The review identifies knowledge gaps around the need to validate findings and address limitations such as small s le sizes. Applying multimodal learning of clinically accessible tests holds strong potential to aid the development of low-cost, reliable, and non-invasive methods for early detection of AD and PD.
Publisher: Elsevier BV
Date: 09-2022
DOI: 10.1016/J.JNS.2022.120336
Abstract: Across the world, Essential Tremor (ET) is the most common tremor diagnosis but up to half of these diagnoses are inaccurate. The misdiagnosis rate is particularly high in late-onset ET, when tremor begins after the age of 60 years. Currently, ET is reported to affect 5.5% of those over 65 years old and 21.7% aged over 95 but there is emerging evidence that late-onset ET has associations with dementia, mortality and more rapid progression. With ageing populations, and a range of new surgical treatments for ET, there is urgent need to clarify whether the clinical manifestations of late-onset ET are the same as for earlier-onset ET. This scoping review used MEDLINE, EMBASE and CINAHL as the information sources of published peer-reviewed research articles between 2011 and 2021. Analysis was done by narrative synthesis. 14 relevant papers were retrieved from studies conducted in Denmark, India, Italy, Germany, Spain and the US and, together, they comprised 7684 participants in total. Compared to older adults with earlier-onset ET, there is evidence that late-onset ET is associated with higher risk of cognitive impairment and dementia, higher mortality rate, faster rate of progression, lack of family history, altered cortical electrical activity, prolonged pupillary responses, and less propensity to demonstrate characteristic alcohol sensitivity. There is evidence that late-onset ET has different clinical manifestations to earlier-onset ET in particular there is higher risk of dementia and mortality. The prognosis is important for clinicians to consider when selecting candidates for deep brain stimulation surgery and also for advanced care planning.
Publisher: Wiley
Date: 08-2023
DOI: 10.1002/GPS.5988
Abstract: Unequal access to cognitive assessments is a major barrier to timely diagnosis, especially for those living in rural or remote areas. ‘One‐stop’ cognitive clinic models are a proposed solution, but few such clinics exist. We evaluate the implementation of a new one‐stop State‐wide clinic model in Tasmania, Australia, where 27% of people live in rural/remote areas. A novel single‐visit protocol has been developed, comprising interdisciplinary medical and cognitive assessments, research participation, consensus diagnosis and management plan. A cross‐sectional evaluation was undertaken using the RE‐AIM (reach, effectiveness, adoption, implementation, maintenance) framework and results benchmarked against the national Australian Dementia Network Registry. Over the first 52 consecutive weekly clinics: Reach : 130 adults were assessed (mean age [SD] 70.12 years [10.31] 59.2% female) with 40 (36.8%) from rural/remote areas. Effectiveness : 98.5% (128/130) received a same‐day diagnosis: 30.1% (n = 40) Subjective Cognitive Decline, 35.4% (46) Mild Cognitive Impairment, 33.1% (43) dementia and one case inconclusive. Adoption : 22.9% (156) of General Practitioners referred patients. Implementation : Nearly all ‘ideal’ diagnostic clinical practices were met and % of surveyed patients reported ‘good/very good’ clinic experience. The wait from referral to diagnosis was 2 months shorter than other national Registry clinics (78 vs. 133 days). This ‘one‐stop’ model provides an interdisciplinary consensus cognitive diagnosis quickly and is well accepted this may reduce health inequities especially for people living in rural/remote areas. This cognitive clinic model may be of relevance to other centres worldwide and also provides a rich data source for research studies.
Publisher: Elsevier BV
Date: 11-2015
Publisher: Institution of Engineering and Technology (IET)
Date: 12-2015
Publisher: IEEE
Date: 06-2019
Publisher: Elsevier BV
Date: 05-2013
DOI: 10.1016/J.BIOSYSTEMS.2013.03.009
Abstract: Artificial biochemical networks (ABNs) are a class of computational dynamical system whose architectures are motivated by the organisation of genetic and metabolic networks in biological cells. Using evolutionary algorithms to search for networks with diagnostic potential, we demonstrate how ABNs can be used to carry out classification when stimulated with time series data collected from human subjects with and without Parkinson's disease. Artificial metabolic networks, composed of coupled discrete maps, offer the best recognition of Parkinsonian behaviour, achieving accuracies in the region of 90%. This is comparable to the diagnostic accuracies found in clinical diagnosis, and is significantly higher than those found in primary and non-expert secondary care. We also illustrate how an evolved classifier is able to recognise erse features of Parkinsonian behaviour and, using perturbation analysis, show that the evolved classifiers have interesting computational behaviours.
Publisher: SCITEPRESS - Science and Technology Publications
Date: 2018
Publisher: BMJ
Date: 14-11-2019
DOI: 10.1136/JNNP-2019-ABN-2.121
Abstract: Botulinum toxin (BoNT) is an effective first-line treatment for cervical dystonia. However, secondary non responsiveness to BoNT treatment remains a key reason for a discontinuation rate of 20%. In 2016 the British Neurotoxin Network (BNN) published recommendations for the management of cervical dystonia patients with poor response to BoNT treatment. To compare management of patients with secondary non responsiveness in two regional neuroscience centres with the BNN guidelines. We retrospectively analysed 68 patients with cervical dystonia who met criteria for secondary non responsiveness to BoNT-A treatment. Suboptimal response to BoNT-A was recorded in 37 patients (54%), whilst 31 (46%) had no therapeutic response. In the ‘suboptimal response’ group, 21 (57%) had a subsequent good therapeutic response with adjustment of dose, muscle selection and injection technique and continued BoNT-A treatment. Of the remainder, 6 (38%) were switched to BoNT-B and 7 (44%) were referred for Deep Brain Stimulation surgery. In the ‘no response’ group 6 patients (19%) had a good therapeutic response with adjustments of dose, muscle selection and injection technique and continued BoNT-A treatment. In this group 22 patients (71%) were assessed for BoNT-A resistance, which was confirmed in 8 (36%). Our audit shows the importance of careful assessment of patients with cervical dystonia presenting with secondary non-reponsiveness to BoNT-A therapy. The BNN recommendations provide a useful framework for improving dystonia treatment.
Publisher: Springer Science and Business Media LLC
Date: 25-09-2017
Publisher: Wiley
Date: 12-2021
DOI: 10.1002/ALZ.058732
Abstract: There is urgent need to develop population‐level digital biomarkers that can detect Alzheimer’s disease (AD) across the continuum, including the preclinical phase. This would allow risk stratification for specialist tests and early recruitment to clinical trials. Motor function declines in the preclinical phase but there has been little exploration of digital motor biomarkers. We have developed ‘TasTest’, an online test that assesses multiple cognitive domains, including movement. The aim of this study was to compare performance on TasTest with subtests of the Cambridge Neuropsychological Test Battery (CANTAB), a validated digital measure of cognitive decline, and determine how performance on the TasTest items varies with age in a large community s le of older adults. The TasTest items include measures of motor control (speed and coordination of keyboard tapping), processing speed (single and choice reaction time), attention and visual perception (identification of an animal in a distorted image), and visuospatial memory (identifying features from delayed recall of a complex figure). A total of 510 adults aged over 50 years (30% male mean 65.5 years SD 7.36), performed TasTest and CANTAB online assessments in their homes. We compared performance on TasTest items to performance on the Paired Associates Learning (PAL) task, which has been previously validated as predictive of accelerated cognitive decline (Barnett et al. 2015, Current Topics in Behavioral Neurosciences, vol 28, Springer, Cham). All TasTest items were significantly associated with PAL scores except the total number of correct responses on the reaction time tasks (Table 1). Several TasTest items had stronger correlations with age than the PAL, these included the keyboard tapping tasks, the number of correctly identified animals on the distorted image, and both simple and choice reaction times (Figure 1). Older people were able to readily complete TasTest tasks remotely from their homes, and performance on most items was significantly associated with scores on a previously validated test of cognition, and correlated with age. TasTest shows potential as a non‐invasive, scalable dementia screening tool.
Publisher: Oxford University Press (OUP)
Date: 06-2008
Abstract: A 61-year-old woman with secondary progressive multiple sclerosis presented on six occasions over a 2-year period with severe hypothermia (31–33.5°C). This resulted in numerous multi-system complications comprising acute pancreatitis, hepatitis, gastrointestinal haemorrhage, psychiatric disturbance, bradycardia, paradoxical sweating, thrombocytopenia, anaemia and raised inflammatory markers. Septic screens were consistently normal. On each occasion she was successfully treated with passive external rewarming and made a complete recovery. This is the first reported case of such extensive sequelae in a single patient with recurrent hypothermic episodes. This unusual patient provides an invaluable insight into the natural history and pathophysiology of hypothermia. The case report is followed by a review of dysfunctional thermoregulation and pathophysiology of hypothermia-induced multi-system complications. A key learning point is to recognise that the clinical manifestations of hypothermia may be widespread and serious but are nonetheless reversible. In addition, one should consider the differential diagnosis of covert hypothermia in those patients with episodic confusion, as hypothermia is under-recognised, particularly in older people, who are prone to accidental hypothermia, and in those with common neurological conditions, such as stroke, head injury and multiple sclerosis, that may have suboptimal thermoregulation.
Publisher: Research Square Platform LLC
Date: 28-03-2023
DOI: 10.21203/RS.3.RS-2694489/V1
Abstract: Background : Behavioural and lifestyle factors contribute almost half of the risk of developing dementia. Addressing these factors might help prevent onset or slow disease progression. Given the rising prevalence and significant costs of dementia, a public health approach targeting these modifiable risk factors is warranted. Methods : The Island Study Linking Ageing and Neurodegenerative Disease (ISLAND) is a large, online, prospective public health research project. Over 13500 residents of Tasmania, Australia, aged 50+ years joined the project between 2019 and 2022, of whom 7270 consented to participate in research. Informed by health behaviour change models, participants’ knowledge, motivations, and behaviours related to modifiable dementia risk are measured at baseline and in annual surveys. Regression and mediation models were used to assess the effects of changes over time, and by exposure to two interventions: a personalised dementia risk profile (DRP) report provided after each survey wave, and the Preventing Dementia Massive Open Online Course (PDMOOC). Results : Data from 3038 participants (mean age 63.7 years, 71.6% female) were used in the reported analyses. The mean number of modifiable dementia risk factors reduced from 1.99 to 1.49 (out of 9) between joining the project and follow-up in 2022. This change was associated with time since baseline and the number of exposures to the DRP (b=-.06, p=.04) and was stronger for PDMOOC participants (b=-.14, p=.02). Markers of dementia risk literacy improved by DRP exposures (from b=.11 to b=.44, p .001) and by PDMOOC engagement (from b=.16 to b=.38, p .001). Six motivational factors changed by DRP exposure (from b=-.04 to b=.04, p’s .021), with stronger effect sizes observed for PDMOOC participants in four factors (from b=-.19 to b=.15, p’s .033). In PDMOOC participants, 13% of the observed behaviour change was mediated by changes in knowledge. Motivating factors – perceived susceptibility and self-efficacy – differentially affect the influence of higher knowledge on behaviour change. Conclusions : The ISLAND project offers a feasible public health framework for improving modifiable risk factors for dementia. The personalised DRP report and engagement with the PDMOOC work synergistically to increase dementia risk literacy and stimulate the intention and self-efficacy for changing risk behaviours.
Publisher: Elsevier BV
Date: 12-2015
Publisher: Elsevier BV
Date: 12-2021
DOI: 10.1016/J.CORTEX.2021.09.018
Abstract: Previous research suggests oral and written language can act as barometers of an in idual's cognitive function, potentially providing a screening tool for the earliest stages of Alzheimer's disease (AD) and other forms of dementia. Idea density is a measure of the rate at which ideas, or elementary predications, are expressed and may provide an ideal measure for early detection of deficits in language. Previous research has shown that when no restrictions are set on the topic of the idea, a decrease in propositional idea density (PID) is associated with an increased risk of developing AD. However, this has been limited by moderate s le sizes and manual transcribing. Technological advancement has enabled the automated calculation of PID from tools such as the Computerized Propositional Idea Density Rater (CPIDR). We delivered an online autobiographical writing task to older adult Australians from ISLAND (Island Study Linking Ageing and Neurodegenerative Disease). Linear regression models were fitted in R. We analysed text files (range 10-1180 words) using CPIDRv5 provided by 3316 (n = 853 males [25.7%], n = 2463 females [74.3%]) ISLAND participants. Over 358,957 words written in 3316 written autobiographical responses were analysed. Mean PID was higher in females (53.5 [±3.69]) than males (52.6 [±4.50]). Both advancing age and being male were significantly associated with a decrease in PID (p < .001). Automated methods of language analysis hold great promise for the early detection of subtle deficits in language capacity. Although our effect sizes were small, PID may be a sensitive measure of deficits in language in ageing in iduals and is able to be collected at scale using online methods of data capture.
Publisher: Springer Science and Business Media LLC
Date: 12-07-2021
Publisher: Wiley
Date: 06-02-2013
DOI: 10.1002/MDS.25335
Abstract: Thirty-four patients have been studied from the time of initiation of pharmacological treatment in a long-term prospective study of levodopa effects and disease progression in Parkinson's disease. Objective motor scoring of the response to levodopa in defined off states was performed every 3 years. The mean time from the initiation of levodopa treatment to the most recent measurements was 18.2 years. Of 8 patients who are still alive, only 3 had none of the features of the advanced disease phase (dementia, hallucinations, frequent falling). Off-phase motor function worsened at a yearly rate of 1.9% of the maximum disability score, although the plots of the serial scores showed that the magnitude of the levodopa response is well preserved. There was little difference in the rate of progression between patients with tremor-dominant and non-tremor-dominant motor subtypes. Those who developed dementia had more rapid deterioration of motor scores, with significantly worse off-phase (P = .008) and on-phase (P = .03) motor function. A graph of serial scores of patients who have died, aligned for time of death, showed an upward curving trend of motor disability in the last 5 years of the disease course. Its advanced phase may reveal that Parkinson's disease has an exponential pattern of progression.
Publisher: BMJ
Date: 09-02-2019
DOI: 10.1136/JNNP-2019-ABN.128
Abstract: Cervical dystonia (CD) is known to be associated with depression and low quality of life (QoL) but we know little about these measures in non-CD patients attending botulinum toxin clinics. The objective was to evaluate the prevalence of depression and low QoL in both CD and nonCD patients. Cross-sectional pilot study. Consecutive patients attending teaching hospital botulinum toxin clinic. Patients completed the Beck’s Depression Inventory (BDI) questionnaire and a Recovering Quality of Life (ReQoL) scale. BDI and ReQoL scores of ≥17 and≤24 indicated depression and impaired QoL respectively. 48 patients (30 female age 45–75 years) were evaluated 33:15 CD:non-CD. The non-CD group comprised hemifacial spasm, upper limb dystonia/tremor, blepharospasm and Meige syndrome. 23% (11/48) of all patients had depression: 27% (9/33) of CD and 13% (2/15) of non-CD. Depression rates were more frequent amongst females and males (27% 17%) (p=0.43). 34% of all patients had low QoL – 36% (12/33) and 27% (4/15) in the CD and non-CD groups respectively (p=0.51). Low QoL scores were more frequent in females (40%) than males (22%) but this difference was not significant (p=0.21). Depression and low quality of life were common in all patients in this pilot study. This suggests that screening of all patients attending botulinum toxin clinics, regardless of their diagnosis, may be clinically important. A larger study is required to validate these findings.
Publisher: Elsevier BV
Date: 04-2007
DOI: 10.1016/J.CLINEURO.2006.11.002
Abstract: Behçet's disease is a chronic relapsing multisystem vasculitis with 49% of cases involving the CNS. Recently there have been two reports of neuro-Behçet's disease (NB) successfully treated with the tumour necrosis factor alpha (TNFalpha) monoclonal antibody infliximab. We describe a patient with longstanding NB who was poorly responsive to azathioprine, cyclosporin, thalidomide and methotrexate. She showed a remarkable response when treated with the recombinant human TNFalpha receptor protein, etanercept. To the best of our knowledge this is the first report of NB successfully treated with etanercept.
Publisher: BMJ
Date: 02-2005
Publisher: Oxford University Press (OUP)
Date: 16-07-2020
Abstract: Parkinson’s disease (PD) is a common neurodegenerative disease. Delayed administration of PD medications is associated with increased risk of life-threatening complications including choking, aspiration pneumonia and neuroleptic malignant syndrome. In 2016, the spouse of a patient with PD wrote to Leeds Teaching Hospitals Trust (LTHT) to highlight that multiple medication delays and omissions had occurred during his recent admission. In response, LTHT formed a PD quality improvement (QI) Collaborative of multidisciplinary members committed to ensuring timely PD medication administration. The faculty used Institute for Healthcare Improvement Model for Improvement QI methodology. Interventions were tested on pilot wards and the most successful were scaled up and spread across all 90 adult inpatient wards as an ‘intervention bundle’. Between January 2016 and June 2020 mean delays in the time from admission to first dose of medication dropped from over 7 to under 1 h. The mean percentage of omitted PD medications reduced from 15.1 to 0.6%. Project success was multifactorial but due to: Simplicity of interventions.Multiprofessional ownership by frontline teams to make changes and take prompt action.The spouse of the patient taking a leading role in the Collaborative, bringing her unique personal insight and experience, which facilitated behavioural change.
Publisher: BMJ
Date: 11-04-2019
DOI: 10.1136/PRACTNEUROL-2019-002233
Abstract: Both multiple system atrophy and Parkinson’s disease may present with parkinsonism and autonomic dysfunction. We describe a patient who initially met the diagnostic criteria for multiple system atrophy and had atypical features for Parkinson’s disease including blackouts and pyramidal signs. Ultimately, he was found to have three separate diagnoses rather than a single unifying one.
Publisher: Wiley
Date: 15-10-2020
DOI: 10.1111/BJHP.12478
Abstract: With few empirically supported treatments, functional movement disorders (FMD) can be challenging to manage. To enable service providers to better support people with FMD, this study sought to understand the lived experience of FMD: to gain insight into how in iduals make sense of their experience from symptom onset through medical evaluation and diagnosis to post‐diagnostic adaptation. An interpretative phenomenological analysis (IPA) of patient accounts of living with FMD. Eight participants were recruited from a UK teaching hospital adult neurology service: seven females, varying in age (20s‐70s), FMD symptom type (tremor, dystonia, and tics), and time to diagnosis (10 ‐ 192 months). Semi‐structured interviews facilitated participant accounts of key events. Interviews lasted 75‐125 minutes and were transcribed verbatim. Three super‐ordinate themes were apparent. The first covered the experiences of onset (‘Something is wrong with me’), including loss of control ‐ with the affected body part often described as a separate entity ‐ threats to identity and disturbance in relationships. ‘At last! What now?’ outlined the bittersweet experience of diagnosis and of treatments. Third, ‘Living my life with it’ incorporated ongoing experiences of coping with symptoms. While some continued to struggle with the emotional impact of symptoms, others developed a compassionate relationship with their self and maintained satisfying activities. FMD has a significant impact on patients’ relationships with themselves and others, which in turn affects well‐being. These findings suggest some nuanced additions to interventions (diagnosis, psychotherapy, physiotherapy, public education.)
Publisher: ACM
Date: 20-07-2016
Publisher: Springer Science and Business Media LLC
Date: 10-12-2022
Publisher: Royal College of General Practitioners
Date: 21-12-2023
Publisher: Springer Science and Business Media LLC
Date: 24-06-2022
DOI: 10.1007/S00415-022-11213-9
Abstract: Isolated REM sleep behaviour disorder (iRBD) is characterised by dream enactment behaviours, such as kicking and punching while asleep, and vivid/violent dreams. It is now acknowledged as a prodromal phase of neurodegenerative disease—approximately 80% of people with iRBD will develop dementia with Lewy Bodies, Parkinson’s disease or another degenerative brain disease within 10 years. It is important that neurologists and other clinicians understand how to make an early accurate diagnosis of iRBD so that affected people can have the opportunity to take part in clinical trials. However, making a diagnosis can be clinically challenging due to a variety of reasons, including delayed referral, symptom overlap with other disorders, and uncertainty about how to confirm a diagnosis. Several methods of assessment are available, such as clinical interview, screening questionnaires and video polysomnography or ‘sleep study’. This review aims to support clinical neurologists in assessing people who present with symptoms suggestive of iRBD. We describe the usefulness and limitations of each diagnostic method currently available in clinical practice, and present recent research on the utility of new wearable technologies to assist with iRBD diagnosis, which may offer a more practical assessment method for clinicians. This review highlights the importance of thorough clinical investigation when patients present with suspected iRBD and emphasises the need for easier access to diagnostic procedures for accurate and early diagnosis.
Publisher: Elsevier BV
Date: 08-2022
Publisher: BMJ
Date: 14-10-2015
DOI: 10.1136/JNNP-2015-312379.173
Abstract: To investigate separable components of finger tapping (FT) of the thumb and index finger in Parkinson's (PD) with normal (PD-NC) and impaired cognition (PD-CI) and in healthy controls (HC). 58 PD and 29 HC performed FT for 30 seconds whilst attached to electromagnetic movement sensors s ling at 60 Hz. All subjects completed the Montreal Cognitive Assessment (MoCA) PD-NC defined as MoCA score ≥26, PD-CI as MoCA score . PD and HC were age-matched. Mean disease duration of PD 6.2 years, Hoehn and Yahr stage 1.9. Mean MoCA score PD 23.1, HC 26.3 (P .001). PD had significantly (P .01) smaller mean velocity and litude of FT, greater decrement of speed and greater variability of rhythm (speed and litude coefficient of variation). Age, disease duration, motor score and levodopa dose were not significantly different between PD-CI (n=36) and PD-NC (n=22). PD-CI had significantly less rhythmic FT movements than PD-NC (P .01) but other parameters were similar. MoCA score was negatively correlated with rhythm in PD (P 0.017). As expected PD have slower, less rhythmic FT movements with greater decrement than HC. Those with PD-CI have significantly less rhythmic movement than those with PD-NC – this finding is currently being investigated.
Publisher: Springer Science and Business Media LLC
Date: 08-09-2021
DOI: 10.1007/S00521-021-06469-7
Abstract: Parkinson’s disease (PD) is a progressive neurodegenerative disorder that causes abnormal movements and an array of other symptoms. An accurate PD diagnosis can be a challenging task as the signs and symptoms, particularly at an early stage, can be similar to other medical conditions or the physiological changes of normal ageing. This work aims to contribute to the PD diagnosis process by using a convolutional neural network, a type of deep neural network architecture, to differentiate between healthy controls and PD patients. Our approach focuses on discovering deviations in patient’s movements with the use of drawing tasks. In addition, this work explores which of two drawing tasks, wire cube or spiral pentagon, are more effective in the discrimination process. With $$93.5\\%$$ 93.5 % accuracy, our convolutional classifier, trained with images of the pentagon drawing task and augmentation techniques, can be used as an objective method to discriminate PD from healthy controls. Our compact model has the potential to be developed into an offline real-time automated single-task diagnostic tool, which can be easily deployed within a clinical setting.
Publisher: BMJ
Date: 14-10-2015
DOI: 10.1136/JNNP-2015-312379.172
Abstract: Clock drawing (CD) requires executive function, attention and visuospatial ability. Our objective was to investigate CD in Parkinson's subjects with and without cognitive impairment. 107 subjects completed the Montreal Cognitive Assessment (MoCA), classifying into normal cognition (PD-NC – MoCA ≥26) and cognitive impairment (PD-CI–MoCA ). CD was scored using MoCA criteria a maximum of 3 points, one each for correct contour, clock face and clock hands. PD-CI (n=57) and PD-NC were matched for all demographics except age (PD-CI were older, P 0.032). 35% of PD-CI scored full marks compared to 90% of PD-NC (sensitivity 0.64, specificity 0.9, age adjusted-odds ratio for predicting PD-CI 15.63, 95% CI 5.18 – 47.62, P .001). 88% of PD-CI scored points for contour and 60% scored points for clock face. In contrast, all PD-NC scored points for contour and clock face (P .001). 42% of PD-CI and 90% of PD-NC correctly drew clock hands (P .001). In this cohort, inability to score maximum points for CD was associated with PD-CI. Correctly drawing clock hands was the hardest component for both groups. Incorrect contour or clock face was highly specific for PD-CI.
Publisher: Oxford University Press (OUP)
Date: 31-08-2015
DOI: 10.1093/BRAIN/AWV232
Publisher: Elsevier BV
Date: 08-2016
Publisher: BMJ
Date: 24-04-2015
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.PARKRELDIS.2018.09.002
Abstract: The long duration response to levodopa in Parkinson's disease outlasts drug elimination by days to weeks. Though a substantive part of anti-parkinsonian motor benefit, it cannot easily be observed. To infer the magnitude of the long duration response during the first decade of Parkinson's disease and identify factors that influence it. Serial practically defined off scores of 24 patients from a longitudinal study of levodopa short duration response were used to establish their rate of motor progression. A line of notional untreated disability (as if drug treatment had never been given) with the same progression gradient was the basis for calculation of the long duration response. Predictors of mean long duration response litude were identified using a multiple linear regression model. Over a mean treatment period of 16.6 ± 4.4 years, annual increase in motor disability was 2.3% of the maximum score. The long duration response composed 49% of total levodopa response during the first decade of treatment, and this proportion was significantly higher soon after commencing levodopa (p = 0.001). Higher pre-treatment motor score (r = 0.60) and lower MMSE (r = 0.60) were the main predictors of a larger long duration response. There was little correlation between long and short duration responses. Long duration responses contribute almost half of the total levodopa benefit during the first decade of treatment. An appreciation of both long and short duration components of drug symptomatic effects is important in clinical trial design to investigate possible neuroprotective treatments.
Publisher: BMJ
Date: 14-10-2015
DOI: 10.1136/JNNP-2015-312379.171
Abstract: To determine which test of visuospatial function – copying a wired cube (‘cube’) or interlocking pentagons (‘pentagons’) – is the best screening tool for detecting cognitive impairment in Parkinson's, as defined by abnormal Montreal Cognitive Assessment (MoCA) score. 107 Parkinson's subjects completed the MoCA and copied pentagons from the Mini-Mental State Examination (MMSE). They were classified into two groups based on MoCA score: (cognitive impairment (CI)) or ≥26 (normal cognition (NC)). Cube and pentagons were scored using MoCA and MMSE criteria. The CI group (n=57) was older (p 0.032) but disease duration, stage and medication were not different. 28% of CI and 72% of NC correctly copied cube. 69% of CI and 92% of NC correctly copied pentagons. Inability to correctly copy cube (p .001) or pentagons (p 0.003) was associated with CI. Age adjusted odds ratio for predicting cognitive impairment was 6.85 (2.97–16.39, p 0.001) for incorrect cube and 4.61 (1.41 – 14.93, p 0.011) for incorrect pentagons. Incorrect cube was the most predictive visuospatial marker of cognitive impairment in Parkinson's. This is potentially useful when assessing cognitive function in a busy outpatient clinic, for ex le. Larger numbers are required for validation.
Publisher: ACM
Date: 15-07-2017
Publisher: Elsevier BV
Date: 11-2023
Publisher: BMJ
Date: 10-03-2117
DOI: 10.1136/PRACTNEUROL-2015-001267
Abstract: People with Parkinson's disease have limited brain reserves of endogenous dopamine thus, their medications must not be omitted or delayed as this may lead to a significant drop in brain dopamine levels. This has two main clinical consequences: first, a deterioration in disease control, with distressing symptoms such as tremor, pain, rigidity, dysphagia and immobility, and second, an increased risk of developing the life-threatening complication of neuroleptic malignant-like syndrome. Common reasons for people with Parkinson's disease being unable to take their oral medications are neurogenic dysphagia from progressive disease or concurrent illness, gastroenteritis, iatrogenic 'nil by mouth' status especially perioperatively, and impaired consciousness level. Here we outline alternative methods to give dopaminergic drugs in the acute setting to people with Parkinson's disease who cannot take their usual oral treatment, namely using dispersible preparations in thickened fluids, an enteral tube, a transdermal patch or subcutaneous injections.
Publisher: ACM
Date: 20-07-2016
Publisher: Elsevier BV
Date: 03-2022
DOI: 10.1016/J.JBI.2022.104030
Abstract: With populations aging, the number of people with dementia worldwide is expected to triple to 152 million by 2050. Seventy percent of cases are due to Alzheimer's disease (AD) pathology and there is a 10-20 year 'pre-clinical' period before significant cognitive decline occurs. We urgently need, cost effective, objective biomarkers to detect AD, and other dementias, at an early stage. Risk factor modification could prevent 40% of cases and drug trials would have greater chances of success if participants are recruited at an earlier stage. Currently, detection of dementia is largely by pen and paper cognitive tests but these are time consuming and insensitive to the pre-clinical phase. Specialist brain scans and body fluid biomarkers can detect the earliest stages of dementia but are too invasive or expensive for widespread use. With the advancement of technology, Artificial Intelligence (AI) shows promising results in assisting with detection of early-stage dementia. This scoping review aims to summarise the current capabilities of AI-aided digital biomarkers to aid in early detection of dementia, and also discusses potential future research directions. In this scoping review, we used PubMed and IEEE Xplore to identify relevant papers. The resulting records were further filtered to retrieve articles published within five years and written in English. Duplicates were removed, titles and abstracts were screened and full texts were reviewed. After an initial yield of 1,463 records, 1,444 records were screened after removal of duplication. A further 771 records were excluded after screening titles and abstracts, and 496 were excluded after full text review. The final yield was 177 studies. Records were grouped into different artificial intelligence based tests: (a) computerized cognitive tests (b) movement tests (c) speech, conversion, and language tests and (d) computer-assisted interpretation of brain scans. In general, AI techniques enhance the performance of dementia screening tests because more features can be retrieved from a single test, there are less errors due to subjective judgements and AI shifts the automation of dementia screening to a higher level. Compared with traditional cognitive tests, AI-based computerized cognitive tests improve the discrimination sensitivity by around 4% and specificity by around 3%. In terms of speech, conversation and language tests, combining both acoustic features and linguistic features achieve the best result with accuracy around 94%. Deep learning techniques applied in brain scan analysis achieves around 92% accuracy. Movement tests and setting smart environments to capture daily life behaviours are two potential future directions that may help discriminate dementia from normal aging. AI-based smart environments and multi-modal tests are promising future directions to improve detection of dementia in the earliest stages.
Publisher: Springer Science and Business Media LLC
Date: 16-08-2018
Publisher: MDPI AG
Date: 14-01-2021
DOI: 10.3390/JPM11010043
Abstract: Introduction: Parkinson’s disease is a heterogeneous clinical syndrome. Parkinson’s disease in older persons presents with a erse array of clinical manifestations leading to unique care needs. This raises the need for the healthcare community to proactively address the care needs of older persons with Parkinson’s disease. Though it is tempting to categorise different phenotypes of Parkinson’s disease, a strong evidence based for the same is lacking. There is considerable literature describing the varying clinical manifestations in old age. This article aims to review the literature looking for strategies in personalising the management of an older person with Parkinson’s disease.
Publisher: Frontiers Media SA
Date: 02-08-2021
DOI: 10.3389/FNAGI.2021.725914
Abstract: Background : The brain-derived neurotrophic factor (BDNF) protein has been shown to have a prominent role in neuron survival, growth, and function in experimental models, and the BDNF Val66Met polymorphism which regulates its expression has been linked to resilience toward the effects of aging on cognition. Cognitively stimulating activity is linked to both increased levels of BDNF in the brain, and protection against age-related cognitive decline. The aim of this study was to investigate the associations between serum BDNF levels, the BDNF Val66Met genotype, and components of cognitive reserve in early and mid-life, measured with the Lifetime of Experiences Questionnaire (LEQ). Methods : Serum BDNF levels were measured cross-sectionally in 156 participants from the Tasmanian Healthy Brain Project (THBP) cohort, a study examining the potential benefits of older adults engaging in a university-level education intervention. Multiple linear regression was used to estimate serum BDNF’s association with age, education, gender, BDNF Val66Met genotype, later-life university-level study, and cognitively stimulating activities measured by the LEQ. Results : Serum BDNF in older adults was associated with early life education and training, increasing 0.007 log(pg/ml) [95%CI 0.001, 0.012] per unit on the LEQ subscale. Conversely, education and training in mid-life were associated with a −0.007 log(pg/ml) [−0.012, −0.001] decrease per unit on the LEQ subscale. Serum BDNF decreased with age (−0.008 log(pg/ml) [−0.015, −0.001] per year), and male gender (−0.109 log(pg/ml) [−0.203, −0.015]), but mean differences between the BDNF Val66Met polymorphisms were not significant ( p = 0.066). All effect sizes were small, with mid-life education and training having the largest effect size ( η p 2 = 0.044). Conclusion : Education in both early and mid-life explained small but significant amounts of variance in serum BDNF levels, more than age or gender. These effects were opposed and independent, suggesting that education at different stages of life may be associated with different cognitive and neural demands. Education at different stages of life may be important covariates when estimating associations between other exposures and serum BDNF.
Publisher: BMJ
Date: 27-05-2022
DOI: 10.1136/JNNP-2022-ABN.276
Abstract: Textbook descriptions of tremulous disorders typically mention the tremor frequencies characteristic of particular conditions, and determination of frequency can aid diagnosis. However, current clinical practice does not involve routine accelerometry or EMG for most tremulous patients, or use of smartphone accel- erometer, and the human eye cannot accurately measure tremor frequency. 37 hand videos were recorded with smartphone camera from 5 essential tremor participants, 10 Parkin- son’s participants and 1 functional tremor participant, either showing a hand resting or held in posture. Tremor was simiultaneously measured using a commercially available accelerometer for clinical use (‘Natus Neurology’). The computing technique of ‘optical flow’ was applied to the smartphone video to measure pixel movement over time in two directions perpendicular to the long axis of the hand. Dominant frequencies were extracted from smartphone video optical flow and from clinic accelerometer data using fast Fourier transform. Bland-Altman analysis showed a mean of the difference in measurements between smartphone video (pixel optical flow) and accelerometer of 0.05 Hz (SD 0.16 Hz) with 95% confidence intervals for this mean difference of -0.26 Hz to +0.36 Hz. We demonstrate excellent agreement between our computing method for smartphone video tremor measurement and the gold standard of accelerometry. Our computing technique suggests that neu- rologists already have ‘point and press’ contactless equipment in their pocket that has the potential to augment routine clinical assessment by measuring tremor frequency. stefanwilliams@doctors.org.uk
Publisher: Springer Science and Business Media LLC
Date: 20-06-2023
DOI: 10.1007/S11357-023-00844-Z
Abstract: Upper limb motor function is a potential new biomarker of cognitive impairment and may aid discrimination from healthy ageing. However, it remains unclear which assessments to use. This study aimed to explore what methods have been used and to describe associations between upper limb function and cognitive impairment. A scoping review was conducted using PubMed, CINAHL and Web of Science. A systematic search was undertaken, including synonyms for key concepts ‘upper limb’, ‘motor function’ and ‘cognitive impairment’. Selection criteria included tests of upper limb motor function and impaired cognition in adults. Analysis was by narrative synthesis. Sixty papers published between 1998 and 2022, comprising 41,800 participants, were included. The most common assessment tasks were finger tapping, Purdue Pegboard Test and functional tasks such as writing. Protocols were erse in terms of equipment used and recording duration. Most participants were recruited from clinical settings. Alzheimer’s Disease was the most common cause of cognitive impairment. Results were mixed but, generally, slower speed, more errors, and greater variability in upper limb movement variables was associated with cognitive impairment. This review maps the upper limb motor function assessments used and summarises the available evidence on how these associate with cognitive impairment. It identifies research gaps and may help guide protocols for future research. There is potential for upper limb motor function to be used in assessments of cognitive impairment.
Publisher: Wiley
Date: 10-01-2023
DOI: 10.1111/BJHP.12643
Abstract: Uncertainty regarding the legitimacy of functional neurological disorder (FND) remains among some health care professionals. Despite treatment guidelines and consensus recommendations, variability in clinical practice referral decisions persists. Evidence from other conditions suggests such clinical decision making is impacted by practitioners' implicit and explicit attitudes. We aimed to identify whether health care professionals hold implicit and/or explicit attitudes about the legitimacy of FND and whether these attitudes are associated with referral decision making. We included 66 health care professionals who work with people with neurological conditions: n = 37 medical doctors, mainly neurologists ( n = 18) and psychiatrists ( n = 10), and n = 29 doctoral level practitioner psychologists. Participants completed an Implicit Association Test (IAT), Implicit Relational Assessment Procedure (IRAP), a referral decision‐making vignette task and self‐report measures of explicit attitudes on FND‐legitimacy, therapeutic optimism and clinician confidence. Multiple Sclerosis (MS) was used as a comparator condition. Participants self‐reported strong explicit FND‐legitimate and MS‐legitimate attitudes but demonstrated an implicit FND‐illegitimate/MS‐legitimate bias. Deeper examination provided by the IRAP data indicated pro‐FND‐legitimate attitudes, but no bias for or against FND‐illegitimate—contrasting the pro‐MS‐legitimate, anti‐MS‐illegitimate attitudes for the comparator condition. Attitudes about FND‐illegitimacy were negatively associated with likelihood of referral to physical interventions such as physiotherapy. Medical doctors had lower treatment optimism and stronger explicit attitudes that FND is illegitimate than psychologists. At an implicit level, clinicians are uncertain about the illegitimacy of FND, and such attitudes are associated with lower likelihood of referral to physiotherapy in particular. Improved education on FND among health care professionals is indicated.
Publisher: Springer Science and Business Media LLC
Date: 04-03-2020
DOI: 10.1186/S40035-020-00187-1
Abstract: The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinician’s Global Impression of Change (CGI-C) after 3 months. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3 months of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3 months, respectively (full analysis set). At 6 months, for UK subgroup only ( n = 95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF (mean ± SD change from baseline: − 3.0 ± 4.6, p 0.0001) and motor scores during ON (− 4.6 ± 8.1, p 0.0001). The mean ± SD improvements of − 3.4 ± 12.8 points for PDQ-8 and -6.8 ± 19.7 points for NMSS were statistically significant versus baseline (both p 0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients. Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice. Registered in July 2016 at clinicaltrials.gov ( NCT02847442 ).
Publisher: Wiley
Date: 16-04-2023
DOI: 10.1002/BRB3.3009
Abstract: Multiple sclerosis (MS) is a chronic demyelinating/neurodegenerative disease associated with change in cognitive function (CF) over time. This systematic review aims to describe the instruments used to measure change in CF over time in people with MS (PwMS). PubMed, OVID, Web of Science, and Scopus databases were searched in English until May 2021. Articles were included if they had at least 100 participants and at least a 1‐year interval between baseline and last follow‐up measurement of CF. Results were quantitatively synthesized, presented in tables and risk of bias was assessed with the Newcastle–Ottawa Scale. Fifty‐seven articles met the inclusion criteria (41,623 PwMS and 1105 controls). An intervention (drug/rehabilitation) was assessed in 22 articles. In the studies that used a test battery, Visual and verbal learning and memory were the most frequently measured domains, but when studies that used test battery or a single test are combined, Information processing speed was the most measured. The Symbol Digit Modalities Test (SDMT) was the most frequently used test as a single test and in a test battery combined. Most studied assessed “change in CF” as cognitive decline defined as 1 or more tests measured as ≥ 1.5 SD from the study control or normative mean in a test battery at baseline and follow‐up. Meta‐analysis of change in SDMT scores with seven articles indicated a nonstatistically significant –0.03 (95% CI –0.14, 0.09) decrease in mean SDMT score per year. This study highlights the slow rate of measured change in cognition in PwMS and emphasizes the lack of a gold standard test and consistency in measuring cognitive change at the population level. More sensitive testing utilizing multiple domains and longer follow‐up may define subgroups where CF change follows different trajectories thus allowing targeted interventions to directly support those where CF is at greatest risk of becoming a clinically meaningful issue
Publisher: BMJ
Date: 14-02-2019
Abstract: Functional neurological disorders are common, but there is a lack of objective tests for these conditions. Although accelerometry can distinguish functional from other tremor types, it is not routinely used at the bedside. Computer vision describes the processing of camera images by computer. It requires only ubiquitous hardware (e.g. smartphone, laptop) and standard clinical assessment, i.e. simple observation. We investigated computer vision to detect tremor distraction/entrainment in functional tremor. Early results comparing computer analysis of video from a functional tremor and an essential tremor. 30 s (60 fps) video of extended forearm was recorded using a smartphone, for a functional tremor and an essential tremor patient. From 15 s, each participant tapped in time with a 3 Hz metronome using the contralateral hand (outside the video frame). Computing algorithms lified the magnitude of video pixel movement and then measured the direction and size of pixel movement over time. After the metronome onset, there was a marked change in video pixel movement for the functional tremor patient, with the frequency concentrating at 3 Hz, and this was statistically significant by linear discriminant analysis. There was no significant change in pixel movement after the metronome for the essential tremor patient (frequency remained 8–12 Hz). Smartphone video pixel movement can detect functional tremor entrainment, suggesting a possible new objective, bedside test.
Publisher: Informa UK Limited
Date: 2018
Publisher: Springer Nature Switzerland
Date: 2023
Publisher: Wiley
Date: 15-12-2009
DOI: 10.1002/MDS.22800
Abstract: In this prospective study of 34 patients with Parkinson's disease (PD), measurements of the short duration levodopa motor response have been performed every 3 years in defined off states. The mean time from initiation of levodopa treatment was 14.8 years, and 17 patients survived to the latest assessment stage. Off phase motor function worsened at a yearly rate of 2.2% of the maximum disability score. The magnitude of the levodopa response is well preserved as the disease progresses, and patients who developed motor fluctuations maintained better on phase motor function than nonfluctuators (P = 0.01). Ten patients, of whom 5 survive, developed dementia. There was no difference in pretreatment disability or initial levodopa response between demented and nondemented subjects. However, dementia was associated with worse on and off motor disability scores after 11 and 14 years (P < 0.001), and a smaller levodopa response magnitude after 14 years (P = 0.008). The plot of sequential scores shows the association between cognitive decline and accelerating increase in motor disability. This suggests that the advanced phase of PD, when Lewy body pathology involves the cerebral cortex, progresses in an exponential rather than linear fashion.
Publisher: Springer International Publishing
Date: 2017
Publisher: Wiley
Date: 16-03-2021
DOI: 10.1002/MDC3.13181
Abstract: Botulinum toxin A (BoNT‐A) is an effective treatment for cervical dystonia. Nevertheless, up to 30% to 40% patients discontinue treatment, often because of poor response. The British Neurotoxin Network (BNN) recently published guidelines on the management of poor response to BoNT‐A in cervical dystonia, but adherence to these guidelines has not yet been assessed. To assess adherence to and usefulness of BNN guidelines in clinical practice. We undertook a retrospective medical notes audit of adherence to the BNN guidelines in 3 United Kingdom tertiary neurosciences centers. Of 76 patients identified with poor response, 42 (55%) had a suboptimal response and, following BNN recommendations, 25 of them (60%) responded to adjustments in BoNT dose, muscle selection or injection technique. Of the remaining 34 (45%) patients with no BoNT response, 20 (59%) were tested for immune resistance, 8 (40%) of whom showed resistance. Fourteen (18%) of all patients were switched to BoNT‐B, and 27 (36%) were referred for deep brain stimulation surgery. In those not immune to BoNT‐A, clinical improvement was seen in 5 (41%) after adjusting their dose and injection technique. Our audit shows that optimizing BoNT dose or injection strategy largely led to improvements in those with suboptimal response and in those reporting no response without resistance. It would be helpful to standardize investigations of potential resistance in those with no therapeutic response.
Publisher: IEEE
Date: 07-2020
Publisher: Wiley
Date: 22-05-2017
DOI: 10.1002/MDC3.12493
Publisher: Royal College of Physicians
Date: 02-2017
Publisher: BMJ
Date: 04-07-2019
DOI: 10.1136/PRACTNEUROL-2019-002205
Abstract: Multiple myeloma is a haematological malignancy with clonal plasma cell proliferation and production of monoclonal immunoglobulins. Its neurological complications are relatively common, caused by both the disease and the treatment. Neurologists should therefore be familiar with its neurological manifestations and complications. We describe a 40-year-old woman who presented with lower cranial neuropathies mimicking variant Guillain-Barré syndrome, with normal brain and spinal cord imaging and cerebrospinal fluid (CSF) albuminocytological dissociation, and subsequently diagnosed with IgD myeloma. She relapsed repeatedly with differing neurological presentations: numb chin syndrome and twice with impaired vision, first from cerebral venous sinus thrombosis and later from leptomeningeal infiltration of the optic chiasm. We discuss the neurological complications of myeloma, emphasising the need to consider it in a wide variety of neurological presentations and repeatedly to reassess its associated neurological diagnoses. We also highlight the complexity of myeloma treatment.
Publisher: Springer Science and Business Media LLC
Date: 18-07-2022
DOI: 10.1186/S12883-022-02772-5
Abstract: The worldwide prevalence of dementia is rapidly rising. Alzheimer’s disease (AD), accounts for 70% of cases and has a 10–20-year preclinical period, when brain pathology covertly progresses before cognitive symptoms appear. The 2020 Lancet Commission estimates that 40% of dementia cases could be prevented by modifying lifestyle/medical risk factors. To optimise dementia prevention effectiveness, there is urgent need to identify in iduals with preclinical AD for targeted risk reduction. Current preclinical AD tests are too invasive, specialist or costly for population-level assessments. We have developed a new online test, TAS Test, that assesses a range of motor-cognitive functions and has capacity to be delivered at significant scale. TAS Test combines two innovations: using hand movement analysis to detect preclinical AD, and computer-human interface technologies to enable robust ‘self-testing’ data collection. The aims are to validate TAS Test to [1] identify preclinical AD, and [2] predict risk of cognitive decline and AD dementia. Aim 1 will be addressed through a cross-sectional study of 500 cognitively healthy older adults, who will complete TAS Test items comprising measures of motor control, processing speed, attention, visuospatial ability, memory and language. TAS Test measures will be compared to a blood-based AD biomarker, phosphorylated tau 181 (p-tau181). Aim 2 will be addressed through a 5-year prospective cohort study of 10,000 older adults. Participants will complete TAS Test annually and subtests of the Cambridge Neuropsychological Test Battery (CANTAB) biennially. 300 participants will undergo in-person clinical assessments. We will use machine learning of motor-cognitive performance on TAS Test to develop an algorithm that classifies preclinical AD risk (p-tau181-defined) and determine the precision to prospectively estimate 5-year risks of cognitive decline and AD. This study will establish the precision of TAS Test to identify preclinical AD and estimate risk of cognitive decline and AD. If accurate, TAS Test will provide a low-cost, accessible enrichment strategy to pre-screen in iduals for their likelihood of AD pathology prior to more expensive tests such as blood or imaging biomarkers. This would have wide applications in public health initiatives and clinical trials. ClinicalTrials.gov Identifier: NCT05194787 , 18 January 2022. Retrospectively registered.
Publisher: Wiley
Date: 07-07-2022
DOI: 10.1002/MDC3.13505
Abstract: The kinematic effects of gestes have not previously been studied. The mechanism(s) by which these sensory tricks modify dystonic movement is not well understood. A kinematic investigation of the geste phenomenon in patients with dystonia. Twenty‐three patients with dystonia associated with a geste were studied. Twenty‐nine healthy controls also participated. Fifteen seconds of finger tapping was recorded by electromagnetic sensors, and the task was repeated with geste . Separable motor components were extracted using a custom‐written MATLAB script. Performance with and without geste was compared using Wilcoxon signed ranks testing. Speed and fluency of finger tapping is impaired in dystonia. When patients executed their geste , speed of movement ( litude × frequency) increased ( P 0.0001), and halts decreased ( P = 0.007). That gestes improve not only dystonic muscle contraction but also the efficiency of voluntary movement suggests a broad influence at the premotor control stage.
Publisher: Springer Science and Business Media LLC
Date: 27-05-2020
DOI: 10.1186/S13063-020-04354-7
Abstract: Parkinson’s disease (PD) affects approximately 145,519 people in the UK. Speech impairments are common with a reported prevalence of 68%, which increase physical and mental demands during conversation, reliance on family and/or carers, and the likelihood of social withdrawal reducing quality of life. In the UK, two approaches to Speech and Language Therapy (SLT) intervention are commonly available: National Health Service (NHS) SLT or Lee Silverman Voice Treatment (LSVT LOUD®). NHS SLT is tailored to the in iduals’ needs per local practice typically consisting of six to eight weekly sessions LSVT LOUD® comprises 16 sessions of in idual treatment with home-based practice over 4 weeks. The evidence-base for their effectiveness is inconclusive. PD COMM is a phase III, multicentre, three-arm, unblinded, randomised controlled trial. Five hundred and forty-six people with idiopathic PD, reporting speech or voice problems will be enrolled. We will exclude those with a diagnosis of dementia, laryngeal pathology or those who have received SLT for speech problems in the previous 2 years. Following informed consent and completion of baseline assessments, participants will be randomised in a 1:1:1 ratio to no-intervention control, NHS SLT or LSVT LOUD® via a central computer-generated programme, using a minimisation procedure with a random element, to ensure allocation concealment. Participants randomised to the intervention groups will start treatment within 4 (NHS SLT) or 7 (LSVT LOUD®) weeks of randomisation. Primary outcome: Voice Handicap Index (VHI) total score at 3 months. Secondary outcomes include: VHI subscales, Parkinson’s Disease Questionnaire-39 Questionnaire on Acquired Speech Disorders EuroQol-5D-5 L ICECAP-O resource utilisation adverse events and carer quality of life. Mixed-methods process and health economic evaluations will take place alongside the trial. Assessments will be completed before randomisation and at 3, 6 and 12 months after randomisation. The trial started in December 2015 and will run for 77 months. Recruitment will take place in approximately 42 sites around the UK. The trial will test the hypothesis that SLT is effective for the treatment of speech or voice problems in people with PD compared to no SLT. It will further test whether NHS SLT or LSVT LOUD® provide greater benefit and determine the cost-effectiveness of both interventions. International Standard Randomised Controlled Trials Number (ISRCTN) Registry, ID: 12421382 . Registered on 18 April 2016.
Publisher: Wiley
Date: 29-04-2011
DOI: 10.1002/MDS.23687
Abstract: This randomized double blind, placebo-controlled crossover study investigated the antidyskinetic effects of levetiracetam in Parkinson's disease. Sixteen participants with levodopa-induced dyskinesia were enrolled. Hourly videotaped dyskinesia assessments scored by the Goetz method and hourly Unified Parkinson's Disease Rating Scale motor subscale scoring were conducted on 1 day at the end of each treatment period. Dyskinesia was slightly less on placebo (P = .26). Patient diary records also showed less dyskinesia on placebo (P = .10). Parkinsonism was a little worse on levetiracetam, at borderline statistical significance (P = .05). Levetiracetam was well tolerated at doses up to 2000 mg per day, but we did not detect any antidyskinetic properties.
Publisher: BMJ
Date: 28-03-2023
Abstract: Functional neurological disorder (FND) is a common and disabling disorder, often misunderstood by clinicians. Although viewed sceptically by some, FND is a diagnosis that can be made accurately, based on positive clinical signs, with clinical features that have remained stable for over 100 years. Despite some progress in the last decade, people with FND continue to suffer subtle and overt forms of discrimination by clinicians, researchers and the public. There is abundant evidence that disorders perceived as primarily affecting women are neglected in healthcare and medical research, and the course of FND mirrors this neglect. We outline the reasons why FND is a feminist issue, incorporating historical and contemporary clinical, research and social perspectives. We call for parity for FND in medical education, research and clinical service development so that people affected by FND can receive the care they need.
Publisher: BMJ
Date: 18-07-2022
Publisher: Oxford University Press (OUP)
Date: 21-08-2008
DOI: 10.1093/BRAIN/AWN019
Abstract: John Ruskin (1819-1900) is chiefly remembered for his works on painting and architecture, and for his powerful and original prose style. In middle age, he suffered recurring episodes of delirium with visual hallucinations and delusions. At about the same time, his writing developed a disjointed polemical character, with cryptic and intemperate elements that disorientated some readers. The nature of Ruskin's 'madness' is a key to understanding his later writing career but the psychiatric explanations given by many of his literary biographers seem unsatisfactory. Ruskin left numerous clues about the illness in his diaries, correspondence and publications. It is likely that he had a relapsing-progressive neurological disorder with neuropsychiatric manifestations. It could have been a fluctuating metabolic or immunological encephalopathy, but the diagnosis that best fits the time course of his illness and the prior history of mood disorder and of migraine with aura is Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). Whatever the pathology, its first effects on frontal lobe function may have actually enhanced Ruskin's creative energy for a long time before stepwise cognitive impairment degraded his ability to write.
Publisher: Center for Open Science
Date: 08-05-2021
Abstract: While upper limb reaches are often made in a feed-forward manner, visual feedbackduring the movement can be used to guide the reaching hand towards a target. InParkinson’s disease (PD), there is evidence that the utilisation of this visual feedbackis increased. However, it is unclear if this is due solely to the characteristic slownessof movements in PD providing more opportunity for incorporating visual feedback tomodify reach trajectories, or whether it is due to cognitive decline impacting (feedforward)movement planning ability. To investigate this, we compared reaction timesand movement times of reaches to a target in groups of PD patients with normalcognition (PD-NC), mild cognitive impairment (PD-MCI) or dementia (PD-D), to that ofcontrols with normal cognition (CON-NC) or mild cognitive impairment (CON-MCI).Reaches were undertaken with full visual feedback (at a ‘natural’ and ‘fast-as-possible’pace) with reduced visual feedback of the reaching limb to an illuminated target andwithout any visual feedback to a remembered target with eyes closed.PD-D exhibited slower reaction times than all other groups across conditions,indicative of less efficient movement planning. When reaching to a rememberedtarget with eyes closed, all PD groups exhibited slower movement times relative totheir natural pace with full visual feedback. Crucially, this relative slowing was mostpronounced for the PD-D group, compared to the PD-MCI and PD-NC groups,suggesting that substantial cognitive decline in PD exacerbates dependence on visualfeedback during upper limb reaches.
Publisher: Elsevier BV
Date: 2021
DOI: 10.2139/SSRN.3979578
Publisher: Elsevier BV
Date: 06-2022
DOI: 10.1016/J.JNS.2022.120251
Abstract: Studies of Functional Neurological Disorders (FND) are usually outpatient-based. To inform service development, we aimed to describe patient pathways through healthcare events, and factors affecting risk of emergency department (ED) reattendance, for people presenting acutely with FND. Acute neurology/stroke teams at a UK city hospital were contacted regularly over 8 months to log FND referrals. Electronic documentation was then reviewed for hospital healthcare events over the preceding 8 years. Patient pathways through healthcare events over time were mapped, and mixed effects logistic regression was performed for risk of ED reattendance within 1 year. In 8 months, 212 patients presented acutely with an initial referral suggesting FND. 20% had subsequent alternative diagnoses, but 162 patients were classified from documentation review as possible (17%), probable (28%) or definite (55%) FND. In the preceding 8 years, these 162 patients had 563 ED attendances and 1693 inpatient nights with functional symptoms, but only 26% were referred for psychological therapy, only 66% had a documented diagnosis, and care pathways looped around ED. Three better practice pathway steps were each associated with lower risk of subsequent ED reattendance: documented FND diagnosis (OR = 0.32, p = 0.004), referral to clinical psychology (OR = 0.35, p = 0.04) and outpatient neurology follow-up (OR = 0.25, p < 0.001). People that present acutely to a UK city hospital with FND tend to follow looping pathways through hospital healthcare events, centred around ED, with low rates of documented diagnosis and referral for psychological therapy. When better practice occurs, it is associated with lower risk of ED reattendance.
Publisher: BMJ
Date: 21-01-2020
DOI: 10.1136/PRACTNEUROL-2019-002335
Abstract: Ageing, genetic, medical and lifestyle factors contribute to the risk of Alzheimer’s disease and other dementias. Around a third of dementia cases are attributable to modifiable risk factors such as physical inactivity, smoking and hypertension. With the rising prevalence and lack of neuroprotective drugs, there is renewed focus on dementia prevention strategies across the lifespan. Neurologists encounter many people with risk factors for dementia and are frequently asked whether lifestyle changes may help. Exercise has emerged as a key intervention for influencing cognition positively, including reducing the risk of age-related cognitive decline and dementia. This article focuses on the current evidence for physical inactivity as a modifiable dementia risk factor and aims to support neurologists when discussing risk reduction.
Publisher: Wiley
Date: 2021
DOI: 10.1002/TRC2.12207
Abstract: Declining cognition in later life is associated with loss of independence and quality of life. This decline in cognition may potentially be reduced or reversed through engaging in cognitively stimulating activities. This study examined the potential for university attendance in later life to enhance cognitive function in older adults. Cognitively unimpaired adults (n = 485, 69% female, median age 60 years) were given the opportunity to undertake free university study. Repeated neurocognitive assessment was performed over 7 years. Participants in the university education group (n = 383) improved z = .02 SD (.01, .03) per year of the study compared to controls ( P = .001 averaged across a battery of cognitive tests). The largest improvements were observed on tests of language and verbal learning, memory, and episodic memory. Later‐life university study was associated with improved cognitive trajectories. Later‐life education may preserve cognitive function, specifically for functions associated with communication, social interaction, and maintaining independence.
Publisher: Elsevier BV
Date: 10-2013
Publisher: BMJ
Date: 31-07-2019
DOI: 10.1136/MEDHUM-2018-011600
Abstract: Though John Ruskin (1819–1900) is remembered principally for his work as a theorist, art critic and historian of visual culture, he wrote exhaustively about his health in his correspondence and diaries. Ruskin was prone to recurring depressive and hypochondriacal feelings in his youth and adulthood. In 1871, at the age of 52 years, he developed an illness with relapsing psychiatric and neurological features. He had a series of attacks of brain disturbance, and a deterioration of his mental faculties affected his writing for years before curtailing his career a decade before he died. Previous writers have suggested he had a psychiatric malady, perhaps schizophrenia or schizoaffective disorder. But the more obvious conclusion from a close medical reading of Ruskin’s descriptions of his illness is he had some sort of ‘organic’ brain illness. This paper aims to give insight into the relationship between Ruskin’s state of well-being and the features of his writing through a palaeographical study of his letters and diary entries. We examine the handwriting for physical traces of Ruskin’s major brain illness, guided by the historical narrative of the illness. We also examine Ruskin’s recording of his experiences for what they reveal about the failure of his health and its impact on his work. Ruskin’s handwriting does not have clear-cut pathological features before around 1885, though suggestions of subtle writing deficits were present as early as 1876. After 1887, Ruskin’s handwriting shows fixed pathological signs—tremor, disturbed letter formation and features that reflect a slow and laborious process of writing. These observations are more than could be explained by normal ageing, and suggest the presence of a neurological deficit affecting writing control. Our findings are consistent with conclusions that we drew from the historical record—that John Ruskin had an organic neurological disorder with cognitive, behavioural, psychiatric and motor effects.
Publisher: Elsevier BV
Date: 10-2013
Publisher: Elsevier BV
Date: 09-2020
Publisher: Springer Science and Business Media LLC
Date: 21-09-2018
Publisher: ACM
Date: 13-07-2019
Publisher: Wiley
Date: 12-2020
DOI: 10.1002/ALZ.045539
Publisher: Elsevier BV
Date: 07-2021
Publisher: IEEE
Date: 12-2016
Publisher: Springer Science and Business Media LLC
Date: 29-09-2023
Publisher: BMJ
Date: 07-08-2011
Publisher: Elsevier BV
Date: 2024
Publisher: MDPI AG
Date: 05-07-2022
DOI: 10.3390/GERIATRICS7040072
Abstract: Figure drawing tasks are commonly used standalone or as part of broader screening tests to detect cognitive impairment. Only one study has compared the classification accuracy of three common drawing tasks—overlapping infinity loops, wire cube, and the clock drawing task (CDT)—in mild cognitive impairment (MCI) and dementia, but age and education, which impact performance, were not accounted for. We replicated the research, adjusting for age and education and, for the first time, assessed subjective cognitive decline (SCD) too. Participants were recruited from the Tasmanian ISLAND Cognitive Clinic and healthy controls from a community s le. All participants completed the three figure drawing tasks. The clinic patients were categorised according to interdisciplinary consensus diagnosis. Binomial logistic regression and area under ROC curves (AUC) were calculated to determine the discriminatory ability of each drawing task. Overall, 112 adults were recruited 51 had normal cognition (NC), 21 SCD, 24 MCI, and 16 had dementia. The infinity loops test did not discriminate any of the groups, casting some doubt on its usefulness. The wire cube discriminated NC from dementia (AUC 0.7 p 0.05). The CDT discriminated NC from dementia (AUC 0.77 p 0.01), NC from cognitive impairment (dementia + MCI AUC 0.59 p 0.05), and MCI from dementia (AUC 0.76 p 0.01). None of the tests discriminated NC from MCI or NC from SCD. The CDT was the most discriminatory test, followed by the wire cube. This may help guide clinicians who often choose just one figure drawing task due to time constraints or patient fatigue.
Publisher: Springer Berlin Heidelberg
Date: 2012
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-01-2023
DOI: 10.1212/WNL.0000000000201369
Abstract: Females have a higher age-adjusted incidence of Alzheimer disease than males but the reasons for this remain unclear. One proposed contributing factor is that, historically, females had less access to education and, therefore, may accumulate less cognitive reserve. However, educational attainment is confounded by IQ, which in itself is a component of cognitive reserve and does not differ between sexes. Steeper age-related cognitive declines are associated with increased risk of dementia. We, therefore, evaluated the moderating effects of 2 proxies for cognitive reserve, education and IQ, on the steepness of age-related declining cognitive trajectories in unimpaired older males and females. The Tasmanian Healthy Brain Project, a long-term cohort study, recruited healthy Australians aged 50–80 years without cognitive impairment. Baseline cognitive reserve was measured using educational history and IQ, measured by the Wechsler Test of Adult Reading, Full Scale Predicted IQ (WTAR-FSIQ). Cognitive trajectories for language, executive function, and episodic and working memory over 5 years were extracted from neuropsychological assessments. The adjusted effects of education, estimated IQ, and APOE allelic variant on cognitive trajectories were compared between males and females. Five hundred sixty-two in iduals (mean [SD] age 60 [6.7] years 68% male 33% APOE ε4+) were followed up over 5 years with 1,924 assessments and 24,946 cognitive test scores (annualized attrition rate 6.6% per year). Estimated IQ correlated with years of education ( p 0.001). Estimated IQ interacted with sex to moderate age-related cognitive trajectories ( p = 0.03 adjusted for education) lower IQ males experienced steeper declining trajectories than higher IQ males, but lower IQ females had similar steepness of declining trajectories to higher IQ females. Education was not associated with rate of cognitive decline ( p = 0.67 adjusted for WTAR-FSIQ). There were no significant differences in age-related cognitive trajectories between APOE genotypes in either sex. IQ, a measure of cognitive reserve, predicted the steepness of declining cognitive trajectories in males only. Education did not explain as much variation in cognitive trajectories as IQ. Our findings do not support the hypothesis that historical sex disparities in access to education contribute to the higher female incidence of Alzheimer disease.
Publisher: MDPI AG
Date: 18-05-2022
DOI: 10.3390/GERIATRICS7030058
Abstract: Most doctors have limited knowledge of dystonia, a movement disorder that can affect people of all ages this contributes to diagnostic delay and poor quality of life. We investigated whether a brief educational intervention could improve knowledge of dystonia amongst medical students. We conducted a systematic review on undergraduate knowledge of dystonia and created an eight-minute video on the condition. We invited medical students at the University of Leeds, UK, to answer 15 multiple choice questions before and immediately after watching the video, and again one month later. Only one previous study specifically assessed medical students’ knowledge of dystonia whilst five others tested their knowledge of movement disorders, or neurology generally, with some questions on dystonia. Of the University of Leeds medical students, 87 (100%), 77 (89%) and 40 (46%) completed the baseline, immediate-recall and delayed-recall questionnaires, respectively. The mean score for students who completed all three questionnaires increased from 7.7 (out of 15) to 12.5 on the immediate-recall questionnaire (p 0.001), and to 10.1 on the delayed-recall questionnaire (p 0.001). At baseline, 76% of students rated their confidence in recognising dystonia as low. After watching the video, 78% rated their confidence as a high, and none rated it low. A brief video improved their knowledge substantially, with sustained effects. This method could be incorporated into medical curricula to reduce diagnostic delays.
Publisher: Elsevier BV
Date: 06-2019
Publisher: Institution of Engineering and Technology (IET)
Date: 1997
DOI: 10.1049/IR:19970104
Publisher: BMJ
Date: 10-2023
Publisher: JMIR Publications Inc.
Date: 04-11-2021
Abstract: p to 40% of incident dementia is considered attributable to behavioral and lifestyle factors. Given the current lack of medical treatments and the projected increase in dementia prevalence, a focus on prevention through risk reduction is needed. e aim to increase dementia risk knowledge and promote changes in dementia risk behaviors at in idual and population levels. he Island Study Linking Aging and Neurodegenerative Disease (ISLAND) is a long-term prospective, web-based cohort study with nested interventions that will be conducted over a 10-year period. Target participants (n=10,000) reside in Tasmania and are aged 50 years or over. Survey data on knowledge, attitudes, and behaviors related to modifiable dementia risk factors will be collected annually. After each survey wave, participants will be provided with a personalized dementia risk profile containing guidelines for reducing risk across 9 behavioral and lifestyle domains and with opportunities to engage in educational and behavioral interventions targeting risk reduction. Survey data will be modeled longitudinally with intervention engagement indices, cognitive function indices, and blood-based biomarkers, to measure change in risk over time. n the initial 12 months (October 2019 to October 2020), 6410 participants have provided baseline data. The study is ongoing. ecruitment targets are feasible and efforts are ongoing to achieve a representative s le. Findings will inform future public health dementia risk reduction initiatives by showing whether, when, and how dementia risk can be lowered through educational and behavioral interventions, delivered in an uncontrolled real-world context. ERR1-10.2196/34688
Publisher: Wiley
Date: 28-12-2020
DOI: 10.1002/MDC3.13119
Publisher: American Medical Association (AMA)
Date: 12-2022
DOI: 10.1001/JAMANEUROL.2022.3718
Abstract: Current treatments manage symptoms of Parkinson disease (PD), but no known treatment slows disease progression. Preclinical and epidemiological studies support the potential use of statins as disease-modifying therapy. To determine whether simvastatin has potential as a disease-modifying treatment for patients with moderate PD. This randomized clinical trial, a double-blind, parallel-group, placebo-controlled futility trial, was conducted between March 2016 and May 2020 within 23 National Health Service Trusts in England. Participants aged 40 to 90 years with a diagnosis of idiopathic PD, with a modified Hoehn and Yahr stage of 3.0 or less while taking medication, and taking dopaminergic medication with wearing-off phenomenon were included. Data were analyzed from May 2020 to September 2020, with additional analysis in February 2021. Participants were allocated 1:1 to simvastatin or matched placebo via a computer-generated random sequence, stratified by site and Hoehn and Yahr stage. In the simvastatin arm, participants entered a 1-month phase of simvastatin, 40 mg daily, followed by 23 months of simvastatin, 80 mg daily, before a 2-month washout period. The prespecified primary outcome was 24-month change in Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) part III score measured while not taking medication (high scores indicate worse outcome). The primary futility analysis included participants who commenced the 80-mg phase and had valid primary outcome data. The safety analysis included all participants who commenced trial treatment and is reported by dose at time of event. Of 332 patients assessed for eligibility, 32 declined and 65 were ineligible. Of 235 recruited participants, 97 (41%) were female, 233 (99%) were White, and the mean (SD) age was 65.4 (9.4) years. A total of 216 patients progressed to the 80-mg dose. Primary outcome analysis (n = 178) indicated the simvastatin group had an additional deterioration in MDS-UPDRS III score while not taking medication at 24 months compared with the placebo group (1.52 points 2-sided 80% CI, −0.77 to 3.80 1-sided futility test P = .006). A total of 37 serious adverse events (AEs), including 3 deaths, and 171 AEs were reported for participants receiving 0-mg simvastatin 37 serious AEs and 150 AEs were reported for participants taking 40 mg or 80 mg of simvastatin. Four participants withdrew from the trial because of an AE. In this randomized clinical trial, simvastatin was futile as a disease-modifying therapy in patients with PD of moderate severity, providing no evidence to support proceeding to a phase 3 trial. ISRCTN Identifier: 16108482
Publisher: Elsevier BV
Date: 02-2022
DOI: 10.1016/J.JOCN.2021.11.005
Abstract: Tomorrow's doctors are unprepared to prevent dementia. This cross-sectional study invited medical students enrolled in the University of Tasmania 5-year medical degree (MBBS) to participate in an online questionnaire during 2019. This study measured students' recall of risk factors, prompted and unprompted, for dementia and cardiovascular disease (CVD), and Dementia Knowledge Assessment Scale (DKAS) score. Data were collected via an online survey comprising the DKAS, and risk factor questions adapted from the Alzheimer's Research UK National Monitor Survey, with questions on CVD risk factors added for comparison. Medical students (n = 82) proffered fewer unprompted risk factors for dementia than for CVD and were less proficient at recognizing dementia risk factors from a prompted list. Knowledge of vascular risk factors for dementia was particularly limited. Their broader dementia knowledge was generally adequate and DKAS scores were at the level of a qualified doctor by final year. Whilst medical students' general knowledge of dementia was satisfactory, their knowledge of modifiable risk factors of dementia was limited. If replicated elsewhere, this raises concerns about whether the future medical workforce is equipped to take a necessary lead role in managing dementia risk reduction. As dementia incidence rises worldwide, and 40% cases are attributable to modifiable risk factors, educational programs may need to urgently address these deficiencies.
Publisher: Oxford University Press (OUP)
Date: 27-03-2018
Publisher: MDPI AG
Date: 12-07-2022
Abstract: This study aimed to investigate the moderating effect of psychological resilience on sleep-deterioration-related depression among patients with prostate cancer, in terms of the total score and in idual symptoms. From a survey of 96 patients with prostate cancer, 55 who reported a deterioration in their sleep quality since diagnosis and treatment completed the Zung Self-Rating Depression Scale, Connor–Davidson Resilience Scale, and the Insomnia Severity Index. Moderation analysis was conducted for the scale total scores and for the ‘core’ symptoms of each scale within this s le, based on data analysis. Interaction analysis was used to identify key associations. The moderation analysis suggested that psychological resilience moderated the depressive effect of sleep deterioration that patients reported occurred after their diagnosis and treatment and did so at the total and ‘core’ symptom levels of being able to see the humorous side of things and to think clearly when under pressure, but there was an interaction between this moderating effect, the strength of psychological resilience, and severity of sleep deterioration. Although it appears to be a successful moderator of depression arising from sleep deterioration that was reported by patients with prostate cancer, the effectiveness of psychological resilience is conditional upon the severity of patients’ sleep difficulties and the strength of their psychological resilience. Implications for the application of resilience training and concomitant therapies for patients with prostate cancer with sleep difficulties and depression are discussed.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-05-2008
Publisher: Elsevier BV
Date: 11-2020
Publisher: Elsevier BV
Date: 10-2023
Publisher: Oxford University Press (OUP)
Date: 07-2022
Abstract: Essential tremor (ET) is the most common cause of tremor in older adults. However, it is increasingly recognised that 30–50% of ET cases are misdiagnosed. Late-onset ET, when tremor begins after the age of 60, is particularly likely to be misdiagnosed and there is mounting evidence that it may be a distinct clinical entity, perhaps better termed ‘ageing-related tremor’. Compared with older adults with early-onset ET, late-onset ET is associated with weak grip strength, cognitive decline, dementia and mortality. This raises questions around whether late-onset ET is a pre-cognitive biomarker of dementia and whether modification of dementia risk factors may be particularly important in this group. On the other hand, it is possible that the clinical manifestations of late-onset ET simply reflect markers of healthy ageing, or frailty, superimposed on typical ET. These issues are important to clarify, especially in the era of specialist neurosurgical treatments for ET being increasingly offered to older adults, and these may not be suitable in people at high risk of cognitive decline. There is a pressing need for clinicians to understand late-onset ET, but this is challenging when there are so few publications specifically focussed on this subject and no specific features to guide prognosis. More rigorous clinical follow-up and precise phenotyping of the clinical manifestations of late-onset ET using accessible computer technologies may help us delineate whether late-onset ET is a separate clinical entity and aid prognostication.
Publisher: Royal College of Physicians
Date: 02-2017
Publisher: Frontiers Media SA
Date: 10-08-2023
DOI: 10.3389/FNINS.2023.1237284
Abstract: Neurofilament light (NfL) is a blood biomarker of neurodegeneration. While serum NfL levels have been demonstrated to increase with normal ageing, the relationship between serum NfL levels and normal age-related changes in cognitive functions is less well understood. The current study investigated whether cross-sectional serum NfL levels measured by single molecule array technology (Simoa®) mediated the effect of age on cognition, measured by a battery of neuropsychological tests administered biannually for 8 years, in a cohort of 174 unimpaired older adults (≥50 years) from the Tasmanian Healthy Brain Project. Mediation analysis was conducted using latent variables representing cognitive test performance on three cognitive domains - episodic memory, executive function, and language (vocabulary, comprehension, naming). Cognitive test scores for the three domains were estimated for each participant, coincident with blood collection in 2018 using linear Bayesian hierarchical models. Higher serum NfL levels were significantly positively associated with age ( p & 0.001 for all domains). Cognitive test scores were significantly negatively associated with age across the domains of executive function ( p & 0.001), episodic memory ( p & 0.001) and language ( p & 0.05). However, serum NfL levels did not significantly mediate the relationship between age and cognitive test scores across any of the domains. This study adds to the literature on the relationship between serum NfL levels and cognition in unimpaired older adults and suggests that serum NfL is not a pre-clinical biomarker of ensuing cognitive decline in unimpaired older adults.
Publisher: Oxford University Press (OUP)
Date: 26-03-2015
DOI: 10.1136/POSTGRADMEDJ-2015-133247
Abstract: Cognitive impairment is a significant non-motor symptom of Parkinson's disease (PD). Longitudinal cohort studies have demonstrated that approximately 50% of those with PD develop dementia after 10 years, increasing to over 80% after 20 years. Deficits in cognition can be identified at the time of PD diagnosis in some patients and this mild cognitive impairment (PD-MCI) has been studied extensively over the last decade. Although PD-MCI is a risk factor for developing Parkinson's disease dementia there is evidence to suggest that PD-MCI might consist of distinct subtypes with different pathophysiologies and prognoses. The major pathological correlate of Parkinson's disease dementia is Lewy body deposition in the limbic system and neocortex although Alzheimer's related pathology is also an important contributor. Pathological damage causes alteration to neurotransmitter systems within the brain, producing behavioural change. Management of cognitive impairment in PD requires a multidisciplinary approach and accurate communication with patients and relatives is essential.
Publisher: SAGE Publications
Date: 08-02-2022
DOI: 10.1177/14713012211067882
Abstract: This paper explores contemporary approaches to balancing truth with the provision of hope during the disclosure of a dementia diagnosis. We discuss the ethical significance of these practices as they relate to each member of the triad – the person, the carer and the clinician – at the point of diagnosis and beyond. The process of disclosing a diagnosis of dementia is complex. It encompasses breaking bad news while balancing hope, with truth about a progressive life-limiting condition. The process of receiving the diagnosis likewise challenges the person who may be unprepared for the diagnosis, while carers seek information and supports. The impact of receiving a diagnosis of dementia can be life-changing and harmful at the personal level – for both the person and carer. This risk of harm becomes a critical consideration for clinicians when deciding on the level of truth: what information should be relayed and to whom? That risk is also balanced against the ethical issue of patient autonomy, which includes the right to know (or not) and make informed decisions about therapeutic interventions. While the consensus is that the autonomy of the person living with dementia must be upheld, controversy exists regarding the extent to which this should occur. For instance, at diagnosis, it is common for clinicians to use euphemisms rather than the word dementia to maintain hope, even though people and carers prefer to know the diagnosis. This practice of therapeutic lying is a pervasive ethical issue in dementia care, made more acceptable by its roots in diagnosis disclosure.
Publisher: Springer International Publishing
Date: 2022
Publisher: Oxford University Press (OUP)
Date: 30-10-2015
DOI: 10.1093/BRAIN/AWV322
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Start Date: 2019
End Date: 2022
Funder: FightMND
View Funded ActivityStart Date: 2022
End Date: 2024
Funder: Royal Hobart Hospital Research Foundation
View Funded ActivityStart Date: 2021
End Date: 2025
Funder: National Health and Medical Research Council
View Funded Activity