scholarly journals Multiple Pathologies are Common in Alzheimer Patients in Clinical Trials

2012 ◽  
Vol 39 (5) ◽  
pp. 592-599 ◽  
Author(s):  
B. W. Wang ◽  
E. Lu ◽  
I. R. A. Mackenzie ◽  
M. Assaly ◽  
C. Jacova ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Mental State ◽  
Rating Scale ◽  
Lewy Bodies ◽  
Screening Tests ◽  
Dementia Patient ◽  
Cognitive Screening ◽  
Multiple Pathology ◽  
Functional Assessments ◽  
Ad Therapy

Objective:To determine the frequency of multiple pathology [Alzheimer Disease (AD) plus Vascular Dementia and/or Dementia with Lewy Bodies] in patients enrolled in clinical trials of AD therapy, and to compare the cognitive and functional assessments between patients with pure AD and AD with multiple pathology.Methods:We conducted a retrospective analysis of patients with a clinical diagnosis of AD who were enrolled in AD therapy clinical trials and subsequently received an autopsy for confirmation of their diagnosis from 2000 to 2009. Performance on cognitive screening tests, namely Modified Mini Mental state (3MS) exam, Mini Mental state Exam (MMSE) and Functional Rating Scale (FRS) were compared between patients with pure AD and multiple pathology.Results:Autopsy reports were available for 16/47 (34%) of deceased patients. Of these 16 patients, 5 (31%) had pure AD pathology, 10 (63%) had AD with other pathology, and 1 (6%) had non-AD pathology. Compared to patients with pure AD, patients with AD mixed with other pathology had poorer baseline FRS in problem-solving (p<0.01) and community affairs (p<0.02).Conclusion:While the strict enrollment criteria for clinical trials identified the presence of AD pathology in the majority of cases (15/16), multiple pathology was more common than pure AD in our series of autopsied patients. Premortem biomarkers that can distinguish between pure AD and AD with multiple pathology will be beneficial in future clinical trials and dementia patient management.

Delirium in older adults: assessment scales review

2011 ◽  
Vol 26 (S2) ◽  
pp. 486-486
Author(s):  
S. Martins ◽  
M.R. Simões ◽  
L. Fernandes
Keyword(s):  
Rating Scale ◽  
Reliability And Validity ◽  
Rapid Onset ◽  
Assessment Method ◽  
Screening Tests ◽  
Cognitive Test ◽  
Cognitive Screening ◽  
Delirium Assessment ◽  
Altered Level ◽  
Assessment Scales

IntroductionDelirium is characterized by the rapid onset of symptoms which fluctuate, with an altered level of consciousness, global disturbance of cognition, perceptual abnormalities and evidence of a physical cause (DSM-IV-R, 2002).AimTo review the characteristics and psychometric properties of thirteen Delirium scales available in research and clinical practice.MethodsMEDLINE database was used to identify the delirium scales in use (1990–2010), using the keywords: delirium, confusion, questionnaires, scales, severity and screening. Only validation studies were included. Exclusion criteria were children and alcohol/drug delirium assessment scales. This study included seven screening scales: Confusion Assessment Method, Intensive Care Delirium Screening Checklist, Delirium Symptom Interview, NEECHAM Confusion Scale, Cognitive Test for Delirium, Delirium Observation Screening, Nursing Delirium Screening Scale and seven severity scales: Delirium Rating Scale, Memorial Delirium Assessment Scale, Confusional State Evaluation, Delirium Severity Scale, Delirium Index and Delirium-O-Meter.ResultsThe majority of scales were based on the Diagnosis Statistical Manual Criteria as well as on a review of selected symptoms of Delirium informed by systematic clinical observation and formal brief assessment of mental status. In most of the studies, for psychometric analysis, the inter-rater reliability and validity with severity of Delirium assessment and cognitive screening tests were used.ConclusionBearing in mind the recent review studies included, we can conclude that CAM is the most widely used instrument for delirium assessment.

scholarly journals Comparison of Approaches for Equating Different Versions of the Mini-Mental State Examination Administered in 22 Studies

2019 ◽  
Vol 188 (12) ◽  
pp. 2202-2212
Author(s):  
Alden L Gross ◽  
Alexandra M Kueider-Paisley ◽  
Campbell Sullivan ◽  
David Schretlen ◽  
Keyword(s):  
Mental State ◽  
Mini Mental State Examination ◽  
Age Groups ◽  
Screening Tests ◽  
Cognitive Screening ◽  
Equipercentile Equating ◽  
Level Data ◽  
Item Level ◽  
Highly Correlated ◽  
State Examination

Abstract The Mini-Mental State Examination (MMSE) is one of the most widely used cognitive screening tests in the world. However, its administration and content differs by country and region, precluding direct comparison of scores across different versions. Our objective was to compare 2 methods of deriving comparable scores across versions of the MMSE. Between 1981 and 2012, investigators in the International Neuropsychological Normative Database Initiative collected MMSE scores on 122,512 persons from 47 studies conducted in 35 countries. We used MMSE data from 80,559 adults aged 41–99 years from 22 studies that provided item-level response data. We first equated 14-point, 15-point, 18-point, 19-point, and 23-point versions of the MMSE to the original 30-point version using coarse equipercentile equating methods that preserved differences across continents, age groups, and durations (years) of education. We then derived more precise item response theory–based scores using item-level responses to MMSE component items. We compared the 2 score-equating approaches using correlation and Bland-Altman plots. Both test-equating approaches were highly correlated with each other (r = 0.73) and with raw MMSE point totals. Bland-Altman plots revealed minimal evidence of systematic differences between the approaches. Our findings support the use of equipercentile equating when item-level data are unavailable to facilitate development of international test norms.

P3-256: The impact of literacy skills on two brief cognitive screening tests: The mini-mental state examination and the brief cognitive battery unbiased by education (BCB-Edu)

2012 ◽  
Vol 8 (4S_Part_15) ◽  
pp. P549-P549
Author(s):  
Maria Teresa Carthery-Goulart ◽  
Maira Oliveira ◽  
Mirna Senaha ◽  
Sonia Brucki ◽  
Lessa Mansur Leticia ◽  
...  
Keyword(s):  
Mental State ◽  
Mini Mental State Examination ◽  
Literacy Skills ◽  
Screening Tests ◽  
Cognitive Screening ◽  
The Impact ◽  
State Examination

scholarly journals Regulator's view on the scientific and regulatory challenges in new mobility outcomes & PROs

2015 ◽  
Author(s):  
Gabriele Schlosser-Weber
Keyword(s):  
Clinical Trials ◽  
Clinical Relevance ◽  
Rating Scale ◽  
Collaborative Work ◽  
Dose Finding ◽  
Innovative Methods ◽  
Functional Assessments ◽  
Clinical Models ◽  
Walking Tests ◽  
Short Time

The current focus from research based pharmaceutical companies is rather on cancer, not CNS. There are several reasons for this, e.g. problems with pre-clinical models, problems with dose-finding, large long-lasting trials, high failure rate, eventually leading to no return on investment. Are the regulatory requirements too high? Certainly not in Multiple Sclerosis, where we had 5 approvals since 2011 (Fingolimod, Fampridine, Teriflunomide, Alemtuzumab, Dimethylfumarate). In parallel we have worked on a new guideline for MS clinical trials, starting with a concept paper in 2011 followed by a large EMA workshop with all relevant stakeholders in 2013. The aim was "to make sure that in the revision of the MS guideline, the EMA can take the most up-to-date, state-of the-art scientific developments in MS into consideration, as well as the positions of experts in the field on the main topics in the guideline". The publication of the final guideline followed in Q2 in 2015 (http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2015/03/WC500185161.pdf). Among other things, we concluded that in the context of long-term outcomes the development of secondary progression is most important. Neither a relapse-based primary endpoint nor an MRI based endpoint can be accepted as a surrogate for disease progression. The EDSS as a rating scale for disability is widely used but has well-known deficiencies, e.g. considerable variability among assessors, that make the interpretation of clinical relevance difficult. However, MS specialists and regulators are familiar with EDSS and it is historically the most frequently used clinician assessment of neurologic impairment in MS clinical trials. Therefore it still will be important to use the EDSS, along with other candidate parameters, to assess true unremitting disability also in future trials to allow comparison among trials. Candidates for other parameters to assess disability are various short-time functional walking tests (e.g. T25-FW, 6MWT) and the MSWS12. Alternative tools to EDSS are currently being developed. Hereby it is important to apply functional assessments for measuring disability in MS. Specific recommendations are not given, but in general the requirements for new tools are that they are reliable, valid, sensitive to change over time, predictive value for disability progression, clinically meaningful and acceptable by the patient. EMA strongly encourages the development of new approaches and innovative methods. EMA intends to apply a flexible approach with regard to the acceptability of positive new endpoints, but a prerequisite is the scientific justification and adequate validation. Qualification procedures are recommended. Collaborative work will be necessary by academia, industry and regulators to develop criteria for appropriate use of PROs in studies, for instance to help assessing clinical relevance.

scholarly journals Regulator's view on the scientific and regulatory challenges in new mobility outcomes & PROs

2015 ◽  
Author(s):  
Gabriele Schlosser-Weber
Keyword(s):  
Clinical Trials ◽  
Clinical Relevance ◽  
Rating Scale ◽  
Collaborative Work ◽  
Dose Finding ◽  
Innovative Methods ◽  
Functional Assessments ◽  
Clinical Models ◽  
Walking Tests ◽  
Short Time

The current focus from research based pharmaceutical companies is rather on cancer, not CNS. There are several reasons for this, e.g. problems with pre-clinical models, problems with dose-finding, large long-lasting trials, high failure rate, eventually leading to no return on investment. Are the regulatory requirements too high? Certainly not in Multiple Sclerosis, where we had 5 approvals since 2011 (Fingolimod, Fampridine, Teriflunomide, Alemtuzumab, Dimethylfumarate). In parallel we have worked on a new guideline for MS clinical trials, starting with a concept paper in 2011 followed by a large EMA workshop with all relevant stakeholders in 2013. The aim was "to make sure that in the revision of the MS guideline, the EMA can take the most up-to-date, state-of the-art scientific developments in MS into consideration, as well as the positions of experts in the field on the main topics in the guideline". The publication of the final guideline followed in Q2 in 2015 (http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2015/03/WC500185161.pdf). Among other things, we concluded that in the context of long-term outcomes the development of secondary progression is most important. Neither a relapse-based primary endpoint nor an MRI based endpoint can be accepted as a surrogate for disease progression. The EDSS as a rating scale for disability is widely used but has well-known deficiencies, e.g. considerable variability among assessors, that make the interpretation of clinical relevance difficult. However, MS specialists and regulators are familiar with EDSS and it is historically the most frequently used clinician assessment of neurologic impairment in MS clinical trials. Therefore it still will be important to use the EDSS, along with other candidate parameters, to assess true unremitting disability also in future trials to allow comparison among trials. Candidates for other parameters to assess disability are various short-time functional walking tests (e.g. T25-FW, 6MWT) and the MSWS12. Alternative tools to EDSS are currently being developed. Hereby it is important to apply functional assessments for measuring disability in MS. Specific recommendations are not given, but in general the requirements for new tools are that they are reliable, valid, sensitive to change over time, predictive value for disability progression, clinically meaningful and acceptable by the patient. EMA strongly encourages the development of new approaches and innovative methods. EMA intends to apply a flexible approach with regard to the acceptability of positive new endpoints, but a prerequisite is the scientific justification and adequate validation. Qualification procedures are recommended. Collaborative work will be necessary by academia, industry and regulators to develop criteria for appropriate use of PROs in studies, for instance to help assessing clinical relevance.

The Colorado Cognitive Assessment (CoCA): Development of an Advanced Neuropsychological Screening Tool

2019 ◽  
Author(s):  
Ashita S. Gurnani ◽  
Shayne S.-H. Lin ◽  
Brandon E Gavett
Keyword(s):  
Construct Validity ◽  
Psychometric Properties ◽  
Cognitive Assessment ◽  
Screening Tool ◽  
Depression Scale ◽  
Internal Consistency Reliability ◽  
Screening Tests ◽  
Cognitive Screening ◽  
Analysis Model ◽  
Factor Analysis Model

Objective: The Colorado Cognitive Assessment (CoCA) was designed to improve upon existing screening tests in a number of ways, including enhanced psychometric properties and minimization of bias across diverse groups. This paper describes the initial validation study of the CoCA, which seeks to describe the test; demonstrate its construct validity; measurement invariance to age, education, sex, and mood symptoms; and compare it to the Montreal Cognitive Assessment (MoCA). Method: Participants included 151 older adults (MAge = 71.21, SD = 8.05) who were administered the CoCA, MoCA, Judgment test from the Neuropsychological Assessment Battery (NAB), 15-item version of the Geriatric Depression Scale (GDS-15), and 10-item version of the Geriatric Anxiety Scale (GAS-10). Results: A single factor confirmatory factor analysis model of the CoCA fit the data well, CFI = 0.955; RMSEA = 0.033. The CoCA’s internal consistency reliability was .84, compared to .74 for the MoCA. The CoCA had stronger disattenuated correlations with the MoCA (r = .79) and NAB Judgment (r = .47) and weaker correlations with the GDS-15 (r = -.36) and GAS-10 (r = -.15), supporting its construct validity. Finally, when analyzed using multiple indicators, multiple causes (MIMIC) modeling, the CoCA showed no evidence of measurement non-invariance, unlike the MoCA. Conclusions: These results provide initial evidence to suggest that the CoCA is a valid cognitive screening tool that offers numerous advantages over the MoCA, including superior psychometric properties and measurement non-invariance. Additional validation and normative studies are warranted.

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