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      Clinical outcome measures in dementia with Lewy bodies trials: critique and recommendations

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          Abstract

          The selection of appropriate outcome measures is fundamental to the design of any successful clinical trial. Although dementia with Lewy bodies (DLB) is one of the most common neurodegenerative conditions, assessment of therapeutic benefit in clinical trials often relies on tools developed for other conditions, such as Alzheimer’s or Parkinson’s disease. These may not be sufficiently valid or sensitive to treatment changes in DLB, decreasing their utility. In this review, we discuss the limitations and strengths of selected available tools used to measure DLB-associated outcomes in clinical trials and highlight the potential roles for more specific objective measures. We emphasize that the existing outcome measures require validation in the DLB population and that DLB-specific outcomes need to be developed. Finally, we highlight how the selection of outcome measures may vary between symptomatic and disease-modifying therapy trials.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s40035-022-00299-w.

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          The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment.

          To develop a 10-minute cognitive screening tool (Montreal Cognitive Assessment, MoCA) to assist first-line physicians in detection of mild cognitive impairment (MCI), a clinical state that often progresses to dementia. Validation study. A community clinic and an academic center. Ninety-four patients meeting MCI clinical criteria supported by psychometric measures, 93 patients with mild Alzheimer's disease (AD) (Mini-Mental State Examination (MMSE) score > or =17), and 90 healthy elderly controls (NC). The MoCA and MMSE were administered to all participants, and sensitivity and specificity of both measures were assessed for detection of MCI and mild AD. Using a cutoff score 26, the MMSE had a sensitivity of 18% to detect MCI, whereas the MoCA detected 90% of MCI subjects. In the mild AD group, the MMSE had a sensitivity of 78%, whereas the MoCA detected 100%. Specificity was excellent for both MMSE and MoCA (100% and 87%, respectively). MCI as an entity is evolving and somewhat controversial. The MoCA is a brief cognitive screening tool with high sensitivity and specificity for detecting MCI as currently conceptualized in patients performing in the normal range on the MMSE.
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            "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician.

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              Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results.

              We present a clinimetric assessment of the Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS). The MDS-UDPRS Task Force revised and expanded the UPDRS using recommendations from a published critique. The MDS-UPDRS has four parts, namely, I: Non-motor Experiences of Daily Living; II: Motor Experiences of Daily Living; III: Motor Examination; IV: Motor Complications. Twenty questions are completed by the patient/caregiver. Item-specific instructions and an appendix of complementary additional scales are provided. Movement disorder specialists and study coordinators administered the UPDRS (55 items) and MDS-UPDRS (65 items) to 877 English speaking (78% non-Latino Caucasian) patients with Parkinson's disease from 39 sites. We compared the two scales using correlative techniques and factor analysis. The MDS-UPDRS showed high internal consistency (Cronbach's alpha = 0.79-0.93 across parts) and correlated with the original UPDRS (rho = 0.96). MDS-UPDRS across-part correlations ranged from 0.22 to 0.66. Reliable factor structures for each part were obtained (comparative fit index > 0.90 for each part), which support the use of sum scores for each part in preference to a total score of all parts. The combined clinimetric results of this study support the validity of the MDS-UPDRS for rating PD.
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                Author and article information

                Contributors
                rodrigfe@musc.edu
                Journal
                Transl Neurodegener
                Transl Neurodegener
                Translational Neurodegeneration
                BioMed Central (London )
                2047-9158
                2 May 2022
                2 May 2022
                2022
                : 11
                : 24
                Affiliations
                [1 ]GRID grid.259828.c, ISNI 0000 0001 2189 3475, Department of Neurology, , Medical University of South Carolina, ; 208b Rutledge Av., Charleston, SC 29403 USA
                [2 ]GRID grid.280625.b, ISNI 0000 0004 0461 4886, Department of Neurology, Center for Memory and Aging, , HealthPartners, ; Saint Paul, MN USA
                [3 ]GRID grid.7080.f, ISNI 0000 0001 2296 0625, Autonomous University of Barcelona, ; Barcelona, Spain
                [4 ]GRID grid.15276.37, ISNI 0000 0004 1936 8091, Fixel Institute for Neurological Diseases, , University of Florida, ; Gainesville, FL USA
                [5 ]GRID grid.4714.6, ISNI 0000 0004 1937 0626, Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences, and Society, Center for Alzheimer’s Research, , Karolinska Institutet, ; Stockholm, Sweden
                [6 ]GRID grid.66875.3a, ISNI 0000 0004 0459 167X, Department of Radiology, , Mayo Clinic, ; Rochester, MN USA
                [7 ]GRID grid.5734.5, ISNI 0000 0001 0726 5157, ARTORG Center for Biomedical Engineering Research, , University of Bern, ; Bern, Switzerland
                [8 ]GRID grid.83440.3b, ISNI 0000000121901201, Dementia Research Centre, , University College London, ; London, UK
                [9 ]GRID grid.4777.3, ISNI 0000 0004 0374 7521, Centre for Public Health, , Queen’s University, ; Belfast, UK
                [10 ]GRID grid.7637.5, ISNI 0000000417571846, Neurology Unit, Department of Clinical and Experimental Sciences, , University of Brescia, ; Brescia, Italy
                [11 ]GRID grid.413782.b, Department of Research and Innovation, , Helse Fonna, Haugesund Hospital, ; Haugesund, Norway
                [12 ]GRID grid.7914.b, ISNI 0000 0004 1936 7443, Institute of Clinical Medicine (K1), , The University of Bergen, ; Bergen, Norway
                [13 ]GRID grid.66875.3a, ISNI 0000 0004 0459 167X, Department of Neurology, Center for Sleep Medicine, , Mayo Clinic, ; Rochester, MN USA
                [14 ]GRID grid.1006.7, ISNI 0000 0001 0462 7212, Translational and Clinical Research Institute, , Newcastle University, ; Newcastle upon Tyne, UK
                [15 ]GRID grid.13097.3c, ISNI 0000 0001 2322 6764, Department of Old Age Psychiatry Institute of Psychiatry Psychology and Neuroscience, , King’s College London, ; London, UK
                [16 ]GRID grid.1013.3, ISNI 0000 0004 1936 834X, ForeFront Parkinson’s Disease Research Clinic, Brain and Mind Centre, School of Medical Sciences, , University of Sydney, ; 100 Mallett Street, Camperdown, NSW 2050 Australia
                Author information
                http://orcid.org/0000-0002-7492-5095
                Article
                299
                10.1186/s40035-022-00299-w
                9059356
                35491418
                53fc3eeb-c927-41f1-b34b-f2dbfc0fa510
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 10 November 2021
                : 31 March 2022
                Categories
                Review
                Custom metadata
                © The Author(s) 2022

                Neurosciences
                dementia with lewy bodies,clinical trials,outcomes,measurement properties
                Neurosciences
                dementia with lewy bodies, clinical trials, outcomes, measurement properties

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