Performance on a pattern separation task by Alzheimer's patients shows possible links between disrupted dentate gyrus activity and apolipoprotein e ∈4 status and cerebrospinal fluid amyloid-β42 levels
Wesnes K.A.,Wesnes Cognition Ltd. |
Wesnes K.A.,Northumbria University |
Wesnes K.A.,Swinburne University of Technology |
Annas P.,Bracket |
And 3 more authors.
Alzheimer's Research and Therapy | Year: 2014
Introduction. Emerging evidence suggests that decreased adult hippocampal neurogenesis represents an early critical event in the course of Alzheimer's disease (AD). In mice, adult neurogenesis is reduced by knock-in alleles for human apolipoprotein E (ApoE) ∈4. Decreased dentate gyrus (DG) neural progenitor cells proliferation has been observed in the triple-transgenic mouse model of AD (3xTg-AD); this reduction being directly associated with the presence of amyloid-β (Aβ) plaques and an increase in the number of Aβ-containing neurons in the hippocampus. Cognitive tasks involving difficult pattern separations have been shown to reflect DG activity and thus potentially neurogenesis in both animals and man. This study involved the administration of a pattern separation paradigm to Alzheimer's patients to investigate relationships between task performance and both ApoE status and cerebrospinal fluid (CSF) Aβ42 levels. Methods. The CDR System pattern separation task involves the presentation of pictures that must later be discriminated from closely similar pictures. This paper presents pattern separation data from 66 mild to moderate AD patients, of which 50 were genotyped and 65 in whom CSF Aβ42 was measured. Results: ApoE ∈4 homozygotes were not compromised on the easy pattern separations compared with the other patients, but they were statistically significantly poorer at the difficult separations. In all patients CSF Aβ42 correlated significantly with the ability to make the difficult discriminations, but not easier discriminations. Pattern separation speed correlated negatively with CSF Aβ42, and thus the association was not due to increased impulsivity. Conclusions: These are, to our knowledge, the first human pattern separation data to suggest a possible genetic link to poor hippocampal neurogenesis in AD, as well as a relationship to Aβ42. Therapies which target neurogenesis may thus be useful in preventing the early stages of AD, notably in ApoE ∈4 homocygotes. © 2014 Wesnes et al.; licensee BioMed Central Ltd.
Wesnes K.A.,Wesnes Cognition Ltd |
Wesnes K.A.,Northumbria University |
Wesnes K.A.,Swinburne University of Technology |
McNamara C.,Bracket |
Journal of Psychopharmacology | Year: 2016
The Cognitive Drug Research (CDR) System is a set of nine computerized tests of attention, information processing, working memory, executive control and episodic memory which was designed for repeated assessments in research projects. The CDR System has been used extensively in clinical trials involving healthy volunteers for over 30 years, and a database of 7751 individuals aged 18-87 years has been accumulated for pre-treatment data from these studies. This database has been analysed, and the relationships between the various scores with factors, including age, gender and years of full-time education, have been identified. These analyses are reported in this paper, along with tables of norms for the various key measures from the core tasks stratified by age and gender. These norms can be used for a variety of purposes, including the determination of eligibility for participation in clinical trials and the everyday relevance of research findings from the system. In addition, these norms provide valuable information on gender differences and the effects of normal ageing on major aspects of human cognitive function. © The Author(s) 2016.
Relationship between working hours and power of attention, memory, fatigue, depression and self-efficacy one year after diagnosis of clinically isolated syndrome and relapsing remitting multiple sclerosis
Jongen P.J.,MS4 Research Institute |
Wesnes K.,Bracket |
Wesnes K.,Swinburne University of Technology |
Van Geel B.,Medisch Centrum Alkmaar |
And 7 more authors.
PLoS ONE | Year: 2014
The role of cognitive domain dysfunction with respect to vocational changes in persons with Clinically Isolated Syndrome (CIS) and early Relapsing Remitting Multiple Sclerosis (eRRMS) is insufficiently known. We investigated thirty-three patients - 14 CIS, 19 eRRMS -, mean (standard deviation [SD]) time since diagnosis 13.5 (4.8) months and mean (SD) Expanded Disability Status Scale (EDSS) score 1.3 (1.1). Patients were assessed on the CDR System, a set of automated tests of cognitive function, which yielded scores for Power of Attention (ms), Continuity of Attention (#), Working Memory (SI), Episodic Memory (#) and Speed of Memory (ms). Work-related items and the confounding variables fatigue, depression, disease impact and self-efficacy, were assessed by self-report questionnaires. Patients had poorer Power of Attention compared to normative data (1187 [161.5] vs. 1070 [98.6]; P<0.0001) and slower Speed of Memory (4043 [830.6]) vs. 2937 [586.1]; P<0.0001). Power of Attention (Pearson r = -0.42; P<0.04), Working Memory (r = 0.42; P<0.04) and depression r = -0.41; P<0.05) correlated with number of days worked per week. Fatigue (r = -0.56; P<0.005), self-efficacy (r = 0.56; P<0.005) and disease impact (r = -0.46; P<0.05) correlated with number of hours worked per week. Persons who wished to work less had poorer Power of Attention (1247 vs. 1116 ms; P<0.02), those who wished to change job had poorer Episodic Memory (1.35 vs. 1.57; p<0.03). People who reduced working hours within 12 months after diagnosis had higher fatigue and disease impact, and lower self-efficacy. The findings of this pilot study indicate that one year after the diagnosis of CIS and RRMS Power of Attention and Speed of Memory are reduced, that Power of Attention and Memory are associated with a capability of working less hours, and that fatigue, depression and disease impact may negatively, and self-efficacy positively affect working hours.
Development of a patient-reported outcome instrument to assess complex activities of daily living and interpersonal functioning in persons with mild cognitive impairment: The qualitative research phase
PubMed | Xcenda, Genentech, ll Center for Studies in Aging, Baylor College of Medicine and 7 more.
Type: Journal Article | Journal: Alzheimer's & dementia : the journal of the Alzheimer's Association | Year: 2016
As drug development research efforts move toward studying patients earlier in the course of Alzheimers disease (AD), it is important to incorporate the patients perspective into measurement of outcomes.This article summarizes the qualitative work of the Patient-Reported Outcome Consortiums Cognition Working Group in the development of a new self-reported outcome measure in persons with mild cognitive impairment (MCI) due to suspected AD, herein referred to as MCI.The draft measure captures the patients voice for two functional domains, complex activities of daily living and interpersonal functioning.This work represents a series of initial steps in the development of this rating scale. The next steps are to conduct psychometric analysis and evaluate the role of insight.
PubMed | Abbvie Inc. and Bracket
Type: Journal Article | Journal: Alcoholism, clinical and experimental research | Year: 2016
ABT-436, a potent and selective arginine vasopressin (AVP) type 1B receptor (V1B ) antagonist, has previously demonstrated basal hypothalamic-pituitary-adrenal (HPA) axis attenuation in man. A V1B antagonist is hypothesized as an alcohol-dependent treatment based on the role of the V1B receptor in stress regulation and the finding that stress is a trigger for relapse in alcoholics. A V1B antagonist has shown favorable effects in rat models of alcohol dependence. A single-dose clinical study was conducted to assess the potential for pharmacokinetic or pharmacodynamic interaction between ABT-436 and alcohol.Twenty moderate alcohol drinkers each received the 4 possible combinations of a single 1,000 mg ABT-436 dose (or matching placebo) and a single 0.5 g/kg alcohol dose (or placebo for alcohol) in a double-blind, randomized, 4-period crossover study. Plasma ABT-436 and blood alcohol levels were measured to assess pharmacokinetic interactions. A computerized cognitive test battery (CDR System), Bond-Lader Visual Analog Scales scales, and a postural stability test were used to measure the effects of alcohol and the potential interaction with ABT-436. The pharmacologic effect of ABT-436 was assessed by measuring serum cortisol.Neither ABT-436 nor alcohol affected the blood levels of the other. Alcohol reduced performance on 2 of 5 CDR System composite variables (power of attention, p = 0.002; quality of secondary episodic memory, p < 0.001), and decreased postural stability (p = 0.043). ABT-436 did not exacerbate those deleterious effects. ABT-436 reduced serum cortisol (p < 0.001), and alcohol did not significantly diminish this expected effect on the HPA axis.No pharmacokinetic or pharmacodynamic interaction between ABT-436 and alcohol was observed.
News Article | December 7, 2016
WAYNE, Pa., Dec. 7, 2016 /PRNewswire/ -- Bracket, a leading clinical trial technology and specialty services provider with expertise in Alzheimer's disease (AD), announced that its Scientific Advisory Board (SAB) has formed an AD sub-committee that will hold its inaugural meeting at the...
News Article | November 17, 2016
WAYNE, Pennsylvania, Nov. 17, 2016 /PRNewswire/ -- Bracket, a leading clinical trial technology and specialty services provider, today announced the strategic acquisition of CLINapps Inc., an international software development and consulting firm that offers a comprehensive supply chain management product suite, designed to meet the unique requirements of biopharmaceuticals management. Effective today, CLINapps will combine its complimentary product offering with the Bracket eClinical suite to deliver a wider range of digital solutions across a trial. With synergies across their individual product offerings, Bracket and CLINapps maintain significant opportunities to revolutionize supply chain management. "CLINapps' strong technology fits squarely into Bracket's goal of transforming the way pharmaceutical companies manage data and interact with sites, investigators and patients," said Jeff Kinell, CEO of Bracket. "We are extremely excited to converge with CLINapps and work to improve how sponsor companies manage their clinical supply chain." CLINapps' product portfolio will be tightly integrated into Bracket's eClinical product suite, adding significantly to the Company's existing Randomization and Trial Supply Management (RTSM) capabilities. SmartSupplies, CLINapps' flagship enterprise clinical trial material management software solutions, will give Bracket the opportunity to manage end-to-end clinical inventory management for sponsors. Bracket's new integrated solution will advance areas of demand planning (forecasting), inventory management, cold chain distribution and controls electronic batch records and overall quality control on the labeling, release, assignment and return of clinical trial materials. "This acquisition marks an exciting opportunity for CLINapps and we are so pleased to have partnered with Bracket to help take our eClinical clinical supplies solutions to the next level," said Tim Elliott, CEO at CLINapps. "Upon recognizing the many synergies that existed, the opportunity to combine our conceptual and innovative solutions was an obvious answer to advancing this life sciences space." Founded in 1999, CLINapps maintains offices in San Diego, California and Hyderabad, India and will continue to operate these locations, expanding Bracket's presence in North America and Asia. To learn more about Bracket, visit www.bracketglobal.com. About CLINapps Established in 1999 with international offices, CLINapps is a fast-growing software development and consulting firm, creating state-of-the-art systems for the pharmaceutical and biotechnology industries. With a full time staff of highly skilled industry professionals, and a strong customer focus, CLINapps has a track record of providing high-quality end-to-end solutions for leading Biotechnology and Pharmaceutical companies. By leveraging our extensive domain knowledge and applying proven technologies, our mission-critical solutions give customers a distinct competitive advantage. About Bracket Bracket, with seven offices and more than 600 employees worldwide, is a clinical trial technology and specialty services provider dedicated to helping biopharmaceutical sponsors and contract research organizations increase the power of their clinical research data by leveraging core competencies in Science, Technology, and Service. Bracket eCOA™ is a flexible platform for electronic clinical outcomes assessments. Bracket RTSM™ is a best-in-breed, scalable and configurable clinical IRT solution for the life sciences industry. Bracket Rater Training and Quality Assurance improve outcomes through customized training and quality assurance programs. Learn more about Bracket at www.bracketglobal.com.
News Article | November 17, 2016
WAYNE, Pa., Nov. 17, 2016 /PRNewswire/ -- Bracket, a leading clinical trial technology and specialty services provider, today announced the strategic acquisition of CLINapps Inc., an international software development and consulting firm that offers a comprehensive supply chain management...
Targum S.D.,Clintara LLC |
Targum S.D.,BrainCells Inc. |
Wedel P.C.,BrainCells Inc. |
Robinson J.,BrainCells Inc. |
And 5 more authors.
Journal of Psychiatric Research | Year: 2013
We compared scores from three different ratings methods in a clinical trial of patients with Major Depressive Disorder (MDD). The Quick Inventory of Depressive Symptoms (QIDS-SR16) was compared to site-based clinician and centralized (site-independent) ratings of the Inventory of Depressive Symptoms (IDSc30). An extracted QIDSc16 was used for a matched comparison with the QIDS-SR16. Patient self-ratings were more depressed at baseline than either site-based ratings (p = 0.131) or centralized ratings (p = 0.005), but significantly less depressed at the end of double-blind treatment than either site-based (p = 0.006) or centralized ratings (p = 0.014), and after 12 weeks (site-based ratings: p = 0.048; centralized ratings: p = 0.004). The matched comparisons with patient self-ratings revealed ICC of r = 0.55 (site-based raters) and r = 0.49 (centralized raters) at baseline. After baseline, the correlations between the two different clinician ratings and patient self-ratings improved to r-values between 0.78 and 0.89. At the end of double-blind treatment, site-based raters separated the combination treatment from placebo on the IDSc30 (p = 0.030) whereas neither centralized ratings nor patient self-ratings achieved statistical significance. Alternatively, patient self-ratings separated the combination treatment from buspirone (p = 0.030) whereas neither clinician rating method achieved significance. A " dual" scoring concordance range reduced the placebo response rate and increased the drug effect between the combination treatment and placebo. These findings reveal scoring variability between each of the three ratings methods and challenge the reliability of any single method to accurately assess symptom severity scores, particularly at baseline. The use of " dual" scoring criteria may help to confirm symptom severity scores and improve ratings precision, particularly prior to enrolling subjects into CNS trials. © 2013 Elsevier Ltd.
PubMed | Bracket and Northumbria University
Type: Journal Article | Journal: Journal of psychopharmacology (Oxford, England) | Year: 2016
The Cognitive Drug Research (CDR) System is a set of nine computerized tests of attention, information processing, working memory, executive control and episodic memory which was designed for repeated assessments in research projects. The CDR System has been used extensively in clinical trials involving healthy volunteers for over 30 years, and a database of 7751 individuals aged 18-87 years has been accumulated for pre-treatment data from these studies. This database has been analysed, and the relationships between the various scores with factors, including age, gender and years of full-time education, have been identified. These analyses are reported in this paper, along with tables of norms for the various key measures from the core tasks stratified by age and gender. These norms can be used for a variety of purposes, including the determination of eligibility for participation in clinical trials and the everyday relevance of research findings from the system. In addition, these norms provide valuable information on gender differences and the effects of normal ageing on major aspects of human cognitive function.