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. 2017 Jun 29;12(6):e0179521.
doi: 10.1371/journal.pone.0179521. eCollection 2017.

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  1 , Derek Groskreutz  2 , Anna Grinbergs-Saull  3 , Rob Howard  1 , John T O'Brien  4 , Gail Mountain  5 , Sube Banerjee  6 , Bob Woods  7 , Robert Perneczky  8   9   10 , Louise Lafortune  11 , Charlotte Roberts  12 , Jenny McCleery  13 , James Pickett  3 , Frances Bunn  14 , David Challis  15 , Georgina Charlesworth  16 , Katie Featherstone  17 , Chris Fox  18 , Claire Goodman  14 , Roy Jones  19 , Sarah Lamb  20 , Esme Moniz-Cook  21 , Justine Schneider  22 , Sasha Shepperd  23 , Claire Surr  24 , Jo Thompson-Coon  25 , Clive Ballard  26 , Carol Brayne  11 , Alistair Burns  27 , Linda Clare  25   28 , Peter Garrard  29 , Patrick Kehoe  30 , Peter Passmore  31 , Clive Holmes  32 , Ian Maidment  33 , Louise Robinson  34 , Gill Livingston  1   35   36
Affiliations

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 et al. PLoS One. .

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.

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Conflict of interest statement

Competing Interests: Professor John O'Brien reports personal fees from GE Healthcare, personal fees from TauRx, personal fees from Cytox, grants and personal fees from Avid/Lilly, personal fees from Axona, personal fees from Pirimal, outside the submitted work. Professor Sube Banerjee reports grants and personal fees from Abbvie, personal fees and non-financial support from Lilly, personal fees from Eleusis, personal fees from Daval International, personal fees from Boehringer-Ingelheim, personal fees from Axovant, personal fees from Lundbeck, personal fees from Nutricia, outside the submitted work; and has been involved as the principal investigator in a series of NIHR grants that has developed the DEMQOL system for the measurement of health related quality of life in dementia. This instrument is available freely and the author receives no financial benefit from its use. Professor Sarah Lamb reports grants from NIHR Health Technology Assessment Programme, during the conduct of the study. Professor Clive Ballard reports grants and personal fees from Lundbeck, grants and personal fees from Acadia, personal fees from Roche, personal fees from Orion, personal fees from GSK, personal fees from Otusaka, personal fees from Heptares, personal fees from Lilly, outside the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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