Suvankar Pal

A systematic review and meta-analysis of retinal nerve fiber layer change in dementia, using optical coherence tomography

Retinal nerve fiber layer (RNFL) thinning, assessed by optical coherence tomography (OCT), has recently been reported in various dementias.

Smartphone- and internet-assisted self-management and adherence tools to manage Parkinson’s disease (SMART-PD): study protocol for a randomised controlled trial (v7; 15 August 2014)

BackgroundNonadherence to treatment leads to suboptimal treatment outcomes and enormous costs to the economy. This is especially important in Parkinson’s disease (PD). The progressive nature of the degenerative process, the complex treatment regimens and the high rates of comorbid conditions make treatment adherence in PD a challenge. Clinicians have limited face-to-face consultation time with PD patients, making it difficult to comprehensively address non-adherence. The rapid growth of digital technologies provides an opportunity to improve adherence and the quality of decision-making during consultation. The aim of this randomised controlled trial (RCT) is to evaluate the impact of using a smartphone and web applications to promote patient self-management as a tool to increase treatment adherence and working with the data collected to enhance the quality of clinical consultation.Methods/DesignA 4-month multicentre RCT with 222 patients will be conducted to compare use of a smartphone- and internet-enabled Parkinson’s tracker smartphone app with treatment as usual for patients with PD and/or their carers. The study investigators will compare the two groups immediately after intervention. Seven centres across England (6) and Scotland (1) will be involved. The primary objective of this trial is to assess whether patients with PD who use the app show improved medication adherence compared to those receiving treatment as usual alone. The secondary objectives are to investigate whether patients who receive the app and those who receive treatment as usual differ in terms of quality of life, quality of clinical consultation, overall disease state and activities of daily living. We also aim to investigate the experience of those receiving the intervention by conducting qualitative interviews with a sample of participants and clinicians, which will be administered by independent researchers.Trial registrationISRCTN45824264 (registered 5 November 2013)

A systematic review and meta-analysis of 18F-labeled amyloid imaging in Alzheimer's disease

Amyloid imaging using fluorine 18–labeled tracers florbetapir, florbetaben, and flutemetamol has recently been reported in Alzheimers disease (AD).

Using a smartphone-based self-management platform to support medication adherence and clinical consultation in Parkinson’s disease

The progressive nature of Parkinson’s disease, its complex treatment regimens and the high rates of comorbid conditions make self-management and treatment adherence a challenge. Clinicians have limited face-to-face consultation time with Parkinson’s disease patients, making it difficult to comprehensively address non-adherence. Here we share the results from a multi-centre (seven centres) randomised controlled trial conducted in England and Scotland to assess the impact of using a smartphone-based Parkinson’s tracker app to promote patient self-management, enhance treatment adherence and quality of clinical consultation. Eligible Parkinson’s disease patients were randomised using a 1:1 ratio according to a computer-generated random sequence, stratified by centre and using blocks of variable size, to intervention Parkinson’s Tracker App or control (Treatment as Usual). Primary outcome was the self-reported score of adherence to treatment (Morisky medication adherence scale −8) at 16 weeks. Secondary outcomes were Quality of Life (Parkinson’s disease questionnaire −39), quality of consultation for Parkinson’s disease patients (Patient-centred questionnaire for Parkinson’s disease), impact on non-motor symptoms (Non-motor symptoms questionnaire), depression and anxiety (Hospital anxiety and depression scale) and beliefs about medication (Beliefs about Medication Questionnaire) at 16 weeks. Primary and secondary endpoints were analysed using a generalised linear model with treatment as the fixed effect and baseline measurement as the covariate. 158 patients completed the study (Parkinson’s tracker app = 68 and TAU = 90). At 16 weeks Parkinson’s tracker app significantly improved adherence, compared to treatment as usual (mean difference: 0.39, 95%CI 0.04–0.74; p = 0.0304) with no confounding effects of gender, number of comorbidities and age. Among secondary outcomes, Parkinson’s tracker app significantly improved patients’ perception of quality of consultation (0.15, 95% CI 0.03 to 0.27; p = 0.0110). The change in non-motor symptoms was −0.82 (95% CI −1.75 to 0.10; p = 0.0822). 72% of participants in the Parkinson’s tracker app group continued to use and engage with the application throughout the 16-week trial period. The Parkinson’s tracker app can be an effective and novel way of enhancing self-reported medication adherence and quality of clinical consultation by supporting self-management in Parkinson’s disease in patients owning smartphones. Further work is recommended to determine whether the benefits of the intervention are maintained beyond the 16 week study period.Digital healthcare: App helps patients stick to planA smartphone-based application improves treatment adherence of patients with Parkinson’s disease (PD). Rashmi Lakshminarayana, from uMotif Ltd, and researchers from the UK and The Netherlands describe the results of a 16 week trial of a Parkinson’s tracker app (PTA) that randomised 215 patients from seven different health centres. Patients using the app reported significantly better adherence to their medication plan compared with control patients who continued their treatment as usual. Interestingly, using the PTA also improved the patients’ perception of the quality of their clinical care, possibly as a result of feeling more involved and in control of their care. These findings suggest that by sending medication reminders and tracking symptoms, the app can help patients with Parkinson’s self-manage their increasingly complex treatment regimen as the disease progresses.

Genetic epidemiology of motor neuron disease-associated variants in the Scottish population

Genetic understanding of motor neuron disease (MND) has evolved greatly in the past 10 years, including the recent identification of association between MND and variants in TBK1 and NEK1. Our aim was to determine the frequency of pathogenic variants in known MND genes and to assess whether variants in TBK1 and NEK1 contribute to the burden of MND in the Scottish population. SOD1, TARDBP, OPTN, TBK1, and NEK1 were sequenced in 441 cases and 400 controls. In addition to 44 cases known to carry a C9orf72 hexanucleotide repeat expansion, we identified 31 cases and 2 controls that carried a loss-of-function or pathogenic variant. Loss-of-function variants were found in TBK1 in 3 cases and no controls and, separately, in NEK1 in 3 cases and no controls. This study provides an accurate description of the genetic epidemiology of MND in Scotland and provides support for the contribution of both TBK1 and NEK1 to MND susceptibility in the Scottish population.

The Utility of the Addenbrooke's Cognitive Examination Version Three in Early-Onset Dementia

Background/Aims: Early-onset dementia (EOD) is defined as functionally relevant cognitive decline with age of onset at less than 65 years. The aim of this study was to investigate the utility of the recently validated third version of the Addenbrookes Cognitive Examination (ACE-III) in predicting dementia diagnoses in EOD. Methods: ACE-III scores of EOD patients were compared to those of healthy controls (HC) and individuals with subjective memory impairment (SMI). Results: The study included 71 EOD patients (Alzheimers disease, n = 31; primary progressive aphasia, n = 11; behavioural-variant frontotemporal dementia, n = 18, and posterior cortical atrophy, n = 11); there were 28 HC and 15 individuals with SMI. At a cut-off score of 88/100, the ACE-III displayed high sensitivity and specificity in distinguishing EOD from HC (91.5 and 96.4%) and SMI (91.5 and 86.7%). Conclusions: The ACE-III is a reliable cognitive screening tool in EOD.

Improved PCR based methods for detecting C9orf72 hexanucleotide repeat expansions.

Due to the GC-rich, repetitive nature of C9orf72 hexanucleotide repeat expansions, PCR based detection methods are challenging. Several limitations of PCR have been reported and overcoming these could help to define the pathogenic range. There is also a need to develop improved repeat-primed PCR assays which allow detection even in the presence of genomic variation around the repeat region. We have optimised PCR conditions for the C9orf72 hexanucleotide repeat expansion, using betaine as a co-solvent and specific cycling conditions, including slow ramping and a high denaturation temperature. We have developed a flanking assay, and repeat-primed PCR assays for both 3′ and 5′ ends of the repeat expansion, which when used together provide a robust strategy for detecting the presence or absence of expansions greater than ∼100 repeats, even in the presence of genomic variability at the 3′ end of the repeat. Using our assays, we have detected repeat expansions in 47/442 Scottish ALS patients. Furthermore, we recommend the combined use of these assays in a clinical diagnostic setting.

The Diagnostic Utility of 99mTc-HMPAO SPECT Imaging: A Retrospective Case Series from a Tertiary Referral Early-Onset Cognitive Disorders Clinic

Background/Aims: Patients with early-onset dementia (EOD) often present atypically, making an accurate diagnosis difficult. Single-photon emission-computed tomography (SPECT) provides an indirect measure of cerebral metabolic activity and can help to differentiate between dementia subtypes. This study aims to investigate the clinical utility of SPECT imaging in the diagnosis of early-onset Alzheimers disease. Methods: All patients attending a tertiary referral clinic specialising in EOD between April 2012 and October 2013 were included in the study. Statistical analysis of SPECT patterns with clinical diagnoses, Addenbrookes Cognitive Examination version 3 scores, and magnetic resonance imaging (MRI) atrophy was undertaken. Results: The results demonstrated a highly significant association between SPECT hypoperfusion patterns and clinical diagnoses. SPECT changes were demonstrated more frequently than MRI atrophy. Conclusions: The results suggest that SPECT imaging may be a useful adjunct to clinical evaluation and a more sensitive biomarker than standard structural imaging.

Investigating Domain-Specific Cognitive Impairment Among Patients With Multiple Sclerosis Using Touchscreen Cognitive Testing in Routine Clinical Care

Cognitive dysfunction is present in up to 70% of patients with multiple sclerosis (MS) and has been reported at all stages and in all subtypes of the disease. These deficits have been reported across a variety of cognitive domains, but are generally under-recognized and incompletely evaluated in routine clinical practice. The aim of this study was to investigate the spectrum of cognitive impairment in patients with MS presenting to a specialist MS clinic using the Cambridge Neuropsychological Test Automated Battery (CANTAB), administered on a touchscreen platform. Ninety MS patients completed computerized CANTAB tasks assessing working memory, executive function, processing speed, attention, and episodic memory. Scores were adjusted for age, sex, and level of education and classified as normal or impaired based on comparison with a large normative data pool. We also investigated the impact of clinical and demographic variables which could potentially influence cognitive performance including patient educational level (a proxy for cognitive reserve), disease status (duration, course, and severity of MS), and depression. CANTAB testing detected cognitive impairment in 40 patients (44% of the sample). The most frequently impaired domain was executive function, present in 55% of cognitively impaired individuals. Disease duration and severity were significantly associated with performance across various cognitive domains. Patients with depressive symptoms were also more likely to exhibit impaired processing speed. Results from this study confirm that cognitive impairment is common and occurs across a range of domains among MS patients attending routine clinical visits. CANTAB tasks provide a sensitive and practical approach to cognitive testing in MS patients as part of a holistic patient assessment.

Corrigendum to “Genetic epidemiology of motor neuron disease-associated variants in the Scottish population.” [Neurobiol. Aging 51 (2017) 178.e11–178.e20]

“The authors thank the patients for consenting to research. In addition, they acknowledge Alona Sosinsky and the Imperial College BRC Genomics facility for bioinformatics support. They acknowledge Generation Scotland for providing control samples and thank Shona Kerr and Archie Campbell for assistance in provision of Generation Scotland samples. The authors acknowledge Cat Graham for providing statistical guidance and also thank David Parry and Sophie Marion de Proce for providing helpful comments on the manuscript.