Core outcome measures for interventions to prevent or slow the progress of dementia for people living with mild to moderate dementia: systematic review and consensus recommendations

Lucy Webster, Derek Groskreutz, Anna Grinbergs-Saull, Rob Howard, John T. O'Brien, Gail Mountain, Sube Banerjee, Bob Woods, Robert Perneczky, Louise Lafortune, Charlotte Roberts, Jenny McCleery, James Pickett, Frances Bunn, David Challis, Georgina Charlesworth, Katie Featherstone, Chris Fox, Claire Goodman, Roy JonesSarah Lamb, Esme Moniz-Cook, Justine Schneider, Sasha Shepperd, Claire Surr, Jo Thompson-Coon, Clive Ballard, Carol Brayne, Alistair Burns, Linda Clare, Peter Garrard, Patrick Kehoe, Peter Passmore, Clive Holmes, Ian Maidment, Louise Robinson, Gill Livingston*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: There are no disease-modifying treatments for dementia. There is also no consensus on disease modifying outcomes. We aimed to produce the first evidence-based consensus on core outcome measures for trials of disease modification in mild-to-moderate dementia.

METHODS AND FINDINGS: We defined disease-modification interventions as those aiming to change the underlying pathology. We systematically searched electronic databases and previous systematic reviews for published and ongoing trials of disease-modifying treatments in mild-to-moderate dementia. We included 149/22,918 of the references found; with 81 outcome measures from 125 trials. Trials involved participants with Alzheimer's disease (AD) alone (n = 111), or AD and mild cognitive impairment (n = 8) and three vascular dementia. We divided outcomes by the domain measured (cognition, activities of daily living, biological markers, neuropsychiatric symptoms, quality of life, global). We calculated the number of trials and of participants using each outcome. We detailed psychometric properties of each outcome. We sought the views of people living with dementia and family carers in three cities through Alzheimer's society focus groups. Attendees at a consensus conference (experts in dementia research, disease-modification and harmonisation measures) decided on the core set of outcomes using these results. Recommended core outcomes were cognition as the fundamental deficit in dementia and to indicate disease modification, serial structural MRIs. Cognition should be measured by Mini Mental State Examination or Alzheimer's Disease Assessment Scale-Cognitive Subscale. MRIs would be optional for patients. We also made recommendations for measuring important, but non-core domains which may not change despite disease modification.

LIMITATIONS: Most trials were about AD. Specific instruments may be superseded. We searched one database for psychometric properties.

INTERPRETATION: This is the first review to identify the 81 outcome measures the research community uses for disease-modifying trials in mild-to-moderate dementia. Our recommendations will facilitate designing, comparing and meta-analysing disease modification trials in mild-to-moderate dementia, increasing their value.

TRIAL REGISTRATION: PROSPERO no. CRD42015027346.

Original languageEnglish
Article numbere0179521
Number of pages22
JournalPLoS ONE
Volume12
Issue number6
DOIs
Publication statusPublished - 29 Jun 2017

Bibliographical note

© 2017 Webster et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

All data available UCL Discovery: http://discovery.ucl.ac.uk/1543119.

Keywords

  • Journal Article

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