Abstract
BackgroundThere 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 findingsWe 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.LimitationsMost trials were about AD. Specific instruments may be superseded. We searched one database for psychometric properties.InterpretationThis 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 registrationPROSPERO no. CRD42015027346.
Highlights
The number of people with dementia is increasing globally
If a treatment that could delay the progression of all mild-to-moderate dementia by 50% became available in 2020, it is estimated that this could reduce the percentage of people living with dementia who are at the severe stage from 14% to 2% by 2050 [4]
We found that trials to date for disease modification in mild to moderate dementia had used 81 different outcome measures
Summary
In the UK it is estimated that a third of people born in 2015 will develop dementia during their lifetime [1]. People living with dementia are currently offered management to improve their symptoms but there are no disease modifying treatments to halt or delay the progression of underlying disease pathologies. If a treatment that could delay the progression of all mild-to-moderate dementia by 50% became available in 2020, it is estimated that this could reduce the percentage of people living with dementia who are at the severe stage from 14% to 2% by 2050 [4]. There are no disease-modifying treatments for dementia. There is 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
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