Outcome measures for Alzheimer's disease: A global inter-societal Delphi consensus

Tim S Ellison¹, Stefano F Cappa^{2

3}, Dawne Garrett⁴, Jean Georges⁵, Takeshi Iwatsubo^{6

7}, Joel H Kramer⁸, Maryna Lehmann⁹, Constantine Lyketsos¹⁰, Andrea B Maier^{11

12

13

14}, Jennifer Merrilees⁸, John C Morris¹⁵, Sharon L Naismith¹⁶, Flavio Nobili^{17

18}, Marco Pahor¹⁹, Dimity Pond²⁰, Louise Robinson²¹, Pinar Soysal^{22

23}, Mathieu Vandenbulcke^{24

25}, Christopher J Weber²⁶, Pieter Jelle Visser^{27

28

29}, Michael Weiner^{30

31}, Giovanni B Frisoni^{32

33}

Affiliations

¹ PharmaGenesis London, London, UK.
² Scuola Universitaria Superiore IUSS Pavia, Pavia, Italy.
³ Dementia Research Center, IRCCS Mondino Foundation, Pavia, Italy.
⁴ Royal College of Nursing, London, UK.
⁵ Alzheimer Europe, Luxembourg, Luxembourg.
⁶ Unit for Early and Exploratory Clinical Development, The University of Tokyo Hospital, Tokyo, Japan.
⁷ Department of Neuropathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
⁸ Department of Neurology, Memory and Aging Center, University of California, San Francisco, California, USA.
⁹ World Dementia Council, George, South Africa.
¹⁰ Richman Family Precision Medicine Center of Excellence in Alzheimer's Disease, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University and Medicine, Baltimore, USA.
¹¹ Department of Medicine and Aged Care, The Royal Melbourne Hospital, The University of Melbourne, Melbourne, Victoria, Australia.
¹² Faculty of Behavioural and Movement Sciences, Department of Human Movement Sciences, Vrije Universiteit, Amsterdam Movement Sciences, Amsterdam, Netherlands.
¹³ Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
¹⁴ Centre for Healthy Longevity, National University Health System, Singapore, Singapore.
¹⁵ Department of Neurology, Washington University, St. Louis, Missouri, USA.
¹⁶ School of Psychology, The University of Sydney, Sydney, New South Wales, Australia.
¹⁷ UO Clinica Neurologica, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Policlinico San Martino, Genova, Italy.
¹⁸ Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Child and Mother Health, University of Genoa, Genova, Italy.
¹⁹ Department of Aging and Geriatric Research, Institute on Aging, University of Florida College of Medicine, Gainesville, Florida, USA.
²⁰ Faculty of Health and Medicine, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.
²¹ Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.
²² Department of Geriatric Medicine, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey.
²³ European Society of Geriatric Medicine, Dementia Special Interest Group.
²⁴ Neuropsychiatry, Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium.
²⁵ Geriatric Psychiatry, University Psychiatric Centre KU Leuven, Leuven, Belgium.
²⁶ Alzheimer's Association, Chicago, Illinois, USA.
²⁷ Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, Netherlands.
²⁸ Alzheimer Center, Department of Neurology, Neuroscience Campus Amsterdam, Amsterdam University Medical Center, VU Medical Center, Amsterdam, Netherlands.
²⁹ Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Karolinska Institute, Stockholm, Sweden.
³⁰ San Francisco Veterans Affairs Medical Center, San Francisco, California, USA.
³¹ Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA.
³² Laboratory of Neuroimaging of Aging (LANVIE), University of Geneva, Geneva, Switzerland.
³³ Memory Clinic, Department of Readaptation and Geriatrics, Geneva University and University Hospitals, Geneva, Switzerland.

PMID: 36749854
PMCID: PMC11010236
DOI: 10.1002/alz.12945

Outcome measures for Alzheimer's disease: A global inter-societal Delphi consensus

Tim S Ellison et al. Alzheimers Dement. 2023 Jun.

. 2023 Jun;19(6):2707-2729.

doi: 10.1002/alz.12945. Epub 2023 Feb 7.

Authors

Affiliations

¹ PharmaGenesis London, London, UK.
² Scuola Universitaria Superiore IUSS Pavia, Pavia, Italy.
³ Dementia Research Center, IRCCS Mondino Foundation, Pavia, Italy.
⁴ Royal College of Nursing, London, UK.
⁵ Alzheimer Europe, Luxembourg, Luxembourg.
⁶ Unit for Early and Exploratory Clinical Development, The University of Tokyo Hospital, Tokyo, Japan.
⁷ Department of Neuropathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
⁸ Department of Neurology, Memory and Aging Center, University of California, San Francisco, California, USA.
⁹ World Dementia Council, George, South Africa.
¹⁰ Richman Family Precision Medicine Center of Excellence in Alzheimer's Disease, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University and Medicine, Baltimore, USA.
¹¹ Department of Medicine and Aged Care, The Royal Melbourne Hospital, The University of Melbourne, Melbourne, Victoria, Australia.
¹² Faculty of Behavioural and Movement Sciences, Department of Human Movement Sciences, Vrije Universiteit, Amsterdam Movement Sciences, Amsterdam, Netherlands.
¹³ Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
¹⁴ Centre for Healthy Longevity, National University Health System, Singapore, Singapore.
¹⁵ Department of Neurology, Washington University, St. Louis, Missouri, USA.
¹⁶ School of Psychology, The University of Sydney, Sydney, New South Wales, Australia.
¹⁷ UO Clinica Neurologica, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Policlinico San Martino, Genova, Italy.
¹⁸ Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Child and Mother Health, University of Genoa, Genova, Italy.
¹⁹ Department of Aging and Geriatric Research, Institute on Aging, University of Florida College of Medicine, Gainesville, Florida, USA.
²⁰ Faculty of Health and Medicine, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.
²¹ Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.
²² Department of Geriatric Medicine, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey.
²³ European Society of Geriatric Medicine, Dementia Special Interest Group.
²⁴ Neuropsychiatry, Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium.
²⁵ Geriatric Psychiatry, University Psychiatric Centre KU Leuven, Leuven, Belgium.
²⁶ Alzheimer's Association, Chicago, Illinois, USA.
²⁷ Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, Netherlands.
²⁸ Alzheimer Center, Department of Neurology, Neuroscience Campus Amsterdam, Amsterdam University Medical Center, VU Medical Center, Amsterdam, Netherlands.
²⁹ Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Karolinska Institute, Stockholm, Sweden.
³⁰ San Francisco Veterans Affairs Medical Center, San Francisco, California, USA.
³¹ Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA.
³² Laboratory of Neuroimaging of Aging (LANVIE), University of Geneva, Geneva, Switzerland.
³³ Memory Clinic, Department of Readaptation and Geriatrics, Geneva University and University Hospitals, Geneva, Switzerland.

PMID: 36749854
PMCID: PMC11010236
DOI: 10.1002/alz.12945

Abstract

Introduction: We aim to provide guidance on outcomes and measures for use in patients with Alzheimer's clinical syndrome.

Methods: A consensus group of 20 voting members nominated by 10 professional societies, and a non-voting chair, used a Delphi approach and modified GRADE criteria.

Results: Consensus was reached on priority outcomes (n = 66), measures (n = 49) and statements (n = 37) across nine domains. A number of outcomes and measurement instruments were ranked for: Cognitive abilities; Functional abilities/dependency; Behavioural and neuropsychiatric symptoms; Patient quality of life (QoL); Caregiver QoL; Healthcare and treatment-related outcomes; Medical investigations; Disease-related life events; and Global outcomes.

Discussion: This work provides indications on the domains and ideal pertinent measurement instruments that clinicians may wish to use to follow patients with cognitive impairment. More work is needed to develop instruments that are more feasible in the context of the constraints of clinical routine.

Keywords: Alzheimer's disease; Delphi; consensus; dementia; measures; outcomes.

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Conflict of interest statement

CONFLICT OF INTEREST

S.F.C. has received speaker fees from, and participated in advisory boards organized by, Biogen, F. Hoffmann-La Roche Ltd., Nutricia. T.S.E. is an employee of PharmaGenesis London, a medical communications consultancy based in the UK. G.B.F. has received funding from the following private donors under the supervision of the Private Foundation of Geneva University Hospitals: A.P.R.A. – Association Suisse pour la Recherche sur la Maladie d’Alzheimer, Genève; Fondation Segré, Genève; Ivan Pictet, Genève; Fondazione Agusta, Lugano; Fondation Chmielewski, Genève; Nicole et René Keller, Genève; Fondation Minkoff, Genève; Race Against Dementia Foundation, London, UK; F. Hoffmann-La Roche Ltd.; OM Pharma; EISAI Pharmaceuticals; Biogen Pharmaceuticals. G.B.F’s competitive research projects are funded by H2020, Innovative Medicines Initiative (IMI), IMI2, Swiss National Science Foundation, and VELUX Foundation. In the past 36 months, G.B.F. has received consulting fees from Biogen, Diadem, F. Hoffmann-La Roche Ltd., and payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing or educational events from Biogen, F. Hoffmann-La Roche Ltd. (all to his institution). G.B.F. reports no conflicts of interest for the current manuscript. D.G. is a former professional lead for older people and dementia care at the Royal College of Nursing, UK, and a board member of the International psychogeriatric Association. J.G. is the Executive Director of Alzheimer Europe, which receives grants and support for its activities from the EU health and research programs and from private and public organizations and institutions. T.I. has served as a consultant or advisory board member for Eisai, Biogen, and F. Hoffmann-La Roche Ltd., and is funded by the Japan Agency for Medical Research and Development. J.H.K. has served as a consultant for Biogen and has received royalties from Pearson, Inc. C.L. has served as a consultant or advisory board member for AstraZeneca, GlaxoSmithKline, Eisai, Novartis, Forest Laboratories, Supernus Pharmaceuticals, Adlyfe, Takeda, Wyeth, Lundbeck, Merz Pharma, Eli Lilly and Company, Pfizer, Genentech, Elan Corporation, NFL Players Association, NFL Benefits Office, Avanir Pharmaceuticals, Zinfandel Pharmaceuticals, Bristol Myers Squibb, Abbvie, Janssen Pharmaceuticals, Orion Pharma, Otsuka Pharmaceutical, Laboratoires Servier, Astellas Pharma, F. Hoffmann-La Roche Ltd., Karuna, SVB Leerink, Maplight Therapeutics, Axsome Therapeutics, Global Institute on Addictions, GW Research Limited, and Merck. A.B.M. has received fees from Abbott Laboratories and Nutricia for serving as a consultant and an advisory board member, and for teaching lessons. J.M. has been funded by National Institutes of Health (NIH) grants #5R0I AF062639, R01 AG0567152, and P01AG019724. J.C.M. has been funded by NIH grants # P30 AG066444, P01AG003991, P01AG026276, U19 AG032438, and U19 AG024904. Neither J.C.M. nor his family owns stock or has equity interest (outside of mutual funds or other externally directed accounts) in any pharmaceutical or biotechnology company. S.L.N. has received fees from Nutricia and F. Hoffmann-La Roche Ltd., for speaking or participating in workshops. S.L.N. is a consultant for Brain Protection Company, and has served as an advisory board member for Alzheimer’s Disease Research Foundation Australia. F.N. has received fees from Bial, Biogen, GE Healthcare, and F. Hoffmann-La Roche Ltd., for teaching lessons and for serving as a consultant and advisory board member. D.P. is an Honorary Professor at the University of Newcastle, Australia, and in the past three years has served as a consultant for Biogen and F. Hoffmann-La Roche Ltd. D.P. is part of a group that runs GP training for Dementia Training Australia. M.L., M.P., L.R., P.S., and M.V. report no conflicts of interest. P.J.V. received a research grant from Biogen, which was paid to the University. C.J.W. is a full-time employee of the Alzheimer’s Association. M.W. has served as a consultant for: Acumen Pharmaceuticals, Alzeca Biosciences, Alzheon, Inc., AlzPath, Anven Biosciences, Baird Equity Capital, BioClinica, Cerecin, Cytox, Dolby Family Ventures, Duke University, Eli Lilly and Company, FUJIFILM-Toyama Chemical Co., Garfield Weston Foundation, Genentech, Guidepoint Global, Indiana University, Japanese Organization for Medical Device Development, Inc. (JOMDD), NervGen Pharma, Nestle/Nestec, NIH, Merck Sharp & Dohme Ltd., PeerView Internal Medicine, Patient-Centered Outcomes Research Institute / Patient-Powered Research Network (PCORI/PPRN), F. Hoffmann-La Roche Ltd., T3D Therapeutics, University of Southern California (USC), Medscape, Eisai, and Vida Ventures. M.W. has acted as a speaker/lecturer for: The Buck Institute for Research on Aging, China Association for Alzheimer’s Disease (CAAD), Japan Society for Dementia Research, and the Korean Dementia Society. M.W. has traveled with support from: the University of Southern California (USC), NervGen Pharma, The American Society of Functional Neuroradiology, and the Clinical Trials on Alzheimer’s Disease conference. M.W. holds stock with Alzeca Biosciences, AlzPath, and Anven Biosciences, and has stock options with Alzheon, Inc. M.W. receives research support from the following sources: NIH; Department of Defense; PCORI; California Department of Public Health; University of Michigan; Siemens; Biogen; The Larry L. Hillblom Foundation; Alzheimer’s Association; The State of California; Johnson & Johnson; Kevin and Connie Shanahan; GE Healthcare; Vanderbilt University Medical Center; Australian Catholic University (Healthy Brain Initiative-Brain Health Registry); The Stroke Foundation; and the Veterans Administration.

Figures

**FIGURE 1**
Delphi consensus process. The steps outlined by Rosenfeld et al. were followed and the GRADE approach was used. The consensus group (n = 18) completed online surveys between April and July 2021 (rounds 1 and 2) and voted anonymously at a live virtual meeting in September 2021 (round 3). Abbreviation: GRADE, Grading of Recommendations Assessment, Development, and Evaluation system

**FIGURE 2**
Systematic literature search strategy for studies reporting outcomes of importance for assessing disease progression in symptomatic Alzheimer’s clinical syndrome published between 26 July 2019 and 1 October 2021 (an update to the searches performed by Tochel et al. 2019). The exclusion criteria were non-English language, review article, editorial, protocol, no human participants (i.e., in vitro or animal studies), not about Alzheimer’s clinical syndrome or mild cognitive impairment, not reporting outcomes of importance to patients, caregivers, or healthcare professionals

See this image and copyright information in PMC

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Outcome measures for Alzheimer's disease: A global inter-societal Delphi consensus

Affiliations

Outcome measures for Alzheimer's disease: A global inter-societal Delphi consensus

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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