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

Federico Rodriguez-Porcel¹, Kathryn A Wyman-Chick², Carla Abdelnour Ruiz³, Jon B Toledo⁴, Daniel Ferreira^{5

6}, Prabitha Urwyler⁷, Rimona S Weil⁸, Joseph Kane⁹, Andrea Pilotto¹⁰, Arvid Rongve^{11

12}, Bradley Boeve¹³, John-Paul Taylor¹⁴, Ian McKeith¹⁴, Dag Aarsland¹⁵, Simon J G Lewis¹⁶; Lewy Body Dementias Clinical Trials Workgroup from the Lewy Body Dementias Professional Interest Area - Alzheimer’s Association International Society to Advance Alzheimer’s Research and Treatment (ISTAART)+

Affiliations

¹ Department of Neurology, Medical University of South Carolina, 208b Rutledge Av., Charleston, SC, 29403, USA. rodrigfe@musc.edu.
² Department of Neurology, Center for Memory and Aging, HealthPartners, Saint Paul, MN, USA.
³ Autonomous University of Barcelona, Barcelona, Spain.
⁴ Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL, USA.
⁵ Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences, and Society, Center for Alzheimer's Research, Karolinska Institutet, Stockholm, Sweden.
⁶ Department of Radiology, Mayo Clinic, Rochester, MN, USA.
⁷ ARTORG Center for Biomedical Engineering Research, University of Bern, Bern, Switzerland.
⁸ Dementia Research Centre, University College London, London, UK.
⁹ Centre for Public Health, Queen's University, Belfast, UK.
¹⁰ Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
¹¹ Department of Research and Innovation, Helse Fonna, Haugesund Hospital, Haugesund, Norway.
¹² Institute of Clinical Medicine (K1), The University of Bergen, Bergen, Norway.
¹³ Department of Neurology, Center for Sleep Medicine, Mayo Clinic, Rochester, MN, USA.
¹⁴ Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
¹⁵ Department of Old Age Psychiatry Institute of Psychiatry Psychology and Neuroscience, King's College London, London, UK.
¹⁶ ForeFront Parkinson's Disease Research Clinic, Brain and Mind Centre, School of Medical Sciences, University of Sydney, 100 Mallett Street, Camperdown, NSW, 2050, Australia.

PMID: 35491418
PMCID: PMC9059356
DOI: 10.1186/s40035-022-00299-w

Review

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

Federico Rodriguez-Porcel et al. Transl Neurodegener. 2022.

. 2022 May 2;11(1):24.

doi: 10.1186/s40035-022-00299-w.

Authors

Affiliations

¹ Department of Neurology, Medical University of South Carolina, 208b Rutledge Av., Charleston, SC, 29403, USA. rodrigfe@musc.edu.
² Department of Neurology, Center for Memory and Aging, HealthPartners, Saint Paul, MN, USA.
³ Autonomous University of Barcelona, Barcelona, Spain.
⁴ Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL, USA.
⁵ Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences, and Society, Center for Alzheimer's Research, Karolinska Institutet, Stockholm, Sweden.
⁶ Department of Radiology, Mayo Clinic, Rochester, MN, USA.
⁷ ARTORG Center for Biomedical Engineering Research, University of Bern, Bern, Switzerland.
⁸ Dementia Research Centre, University College London, London, UK.
⁹ Centre for Public Health, Queen's University, Belfast, UK.
¹⁰ Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
¹¹ Department of Research and Innovation, Helse Fonna, Haugesund Hospital, Haugesund, Norway.
¹² Institute of Clinical Medicine (K1), The University of Bergen, Bergen, Norway.
¹³ Department of Neurology, Center for Sleep Medicine, Mayo Clinic, Rochester, MN, USA.
¹⁴ Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
¹⁵ Department of Old Age Psychiatry Institute of Psychiatry Psychology and Neuroscience, King's College London, London, UK.
¹⁶ ForeFront Parkinson's Disease Research Clinic, Brain and Mind Centre, School of Medical Sciences, University of Sydney, 100 Mallett Street, Camperdown, NSW, 2050, Australia.

PMID: 35491418
PMCID: PMC9059356
DOI: 10.1186/s40035-022-00299-w

Erratum in

Correction: Clinical outcome measures in dementia with Lewy bodies trials: critique and recommendations.
Rodriguez-Porcel F, Wyman-Chick KA, Abdelnour Ruiz C, Toledo JB, Ferreira D, Urwyler P, Weil RS, Kane J, Pilotto A, Rongve A, Boeve B, Taylor JP, McKeith I, Aarsland D, Lewis SJG; Lewy Body Dementias Clinical Trials Workgroup from the Lewy Body Dementias Professional Interest Area - Alzheimer’s Association International Society to Advance Alzheimer’s Research and Treatment (ISTAART)+. Rodriguez-Porcel F, et al. Transl Neurodegener. 2022 May 17;11(1):29. doi: 10.1186/s40035-022-00306-0. Transl Neurodegener. 2022. PMID: 35578366 Free PMC article. No abstract available.

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.

Keywords: Clinical trials; Dementia with Lewy bodies; Measurement properties; Outcomes.

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Conflict of interest statement

The authors declare that they have no competing interests.

References

1. Vann Jones SA, O'Brien JT. The prevalence and incidence of dementia with Lewy bodies: a systematic review of population and clinical studies. Psychol Med. 2014;44(4):673–683. doi: 10.1017/S0033291713000494. - DOI - PubMed
1. Mueller C, Ballard C, Corbett A, Aarsland D. The prognosis of dementia with Lewy bodies. Lancet Neurol. 2017;16(5):390–398. doi: 10.1016/S1474-4422(17)30074-1. - DOI - PubMed
1. Senkevich K, Rudakou U, Gan-Or Z. New therapeutic approaches to Parkinson's disease targeting GBA, LRRK2 and Parkin. Neuropharmacology. 2022;202:108822. doi: 10.1016/j.neuropharm.2021.108822. - DOI - PubMed
1. Usman MB, Bhardwaj S, Roychoudhury S, Kumar D, Alexiou A, Kumar P, et al. Immunotherapy for Alzheimer's disease: current scenario and future perspectives. J Prev Alzheimers Dis. 2021;8(4):534–551. - PubMed
1. Patel B, Irwin DJ, Kaufer D, Boeve BF, Taylor A, Armstrong MJ. Outcome measures for dementia with Lewy body clinical trials: a review. Alzheimer Dis Assoc Disord. 2021;6:66. - PMC - PubMed

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

Affiliations

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

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical