Diagnosing Mild Cognitive Impairment (MCI) in clinical trials: a systematic review Blossom Christa Maree Stephan, 1 Thais Minett, 2 Emma Pagett, 2 Mario Siervo, 3 Carol Brayne, 2 Ian G McKeith 3 To cite: Christa Maree Stephan B, Minett T, Pagett E, et al. Diagnosing Mild Cognitive Impairment (MCI) in clinical trials: a systematic review. BMJ Open 2013;3:e001909. doi:10.1136/bmjopen-2012- 001909 ▸ Prepublication history and additional material for this paper are available online. To view these files please visit the journal online (http://dx.doi.org/10.1136/ bmjopen-2012-001909). Received 15 August 2012 Revised 7 January 2013 Accepted 9 January 2013 This final article is available for use under the terms of the Creative Commons Attribution Non-Commercial 2.0 Licence; see http://bmjopen.bmj.com 1 Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK 2 Department of Public Health and Primary Care, Cambridge University, Cambridge, UK 3 Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK Correspondence to Dr Blossom Christa Maree Stephan; blossom.stephan@ncl.ac.uk ABSTRACT Objective: To describe how criteria for amnestic Mild Cognitive Impairment (aMCI) have been operationalised in randomised controlled clinical trials (RCTs). Design: Systematic review. Information sources: EMBASE, PubMed and PSYCHInfo were searched from their inception to February 2012. Electronic clinical trial registries were also searched (February 2012). Study selection: RCTs were included where participant selection was made using Petersen et al-defined aMCI. There was no restriction on intervention type or the outcome tested. Data extraction: For each trial, we extracted information on study design, demographics, exclusion criteria and the operationalisation strategy for the five aMCI diagnostic criteria including: (1) memory complaint, (2) normal general cognitive function, (3) memory impairment, (4) no functional impairment and (5) no dementia. Results: 223 articles and 278 registered trials were reviewed, of which 22 met inclusion criteria. Various methods were applied for operationalising aMCI criteria resulting in variability in participant selection. Memory complaint and assessment of general cognitive function were the most consistently measured criteria. There was large heterogeneity in the neuropsychological methods used to determine memory impairment. It was not possible to assess the impact of these differences on case selection accuracy for dementia prediction. Further limitations include selective and unclear reporting of how each of the criteria was measured. Conclusions: The results highlight the urgent need for a standardised approach to map aMCI. Lack of uniformity in clinical diagnosis, however, is not exclusively a problem for MCI but also for other clinical states such as dementia including Alzheimer’s disease, Lewy Body, frontotemporal or vascular dementia. Defining a uniform approach to MCI classification, or indeed for any classification concept within the field of dementia, should be a priority if further trials are to be undertaken in the older aged population based on these concepts. INTRODUCTION As new preventative strategies for dementia are developed, methods to select persons accurately for clinical trial involvement will be needed. In this perspective, Mild Cognitive Impairment (MCI), an intermediate state between normal ageing and dementia, has ARTICLE SUMMARY Article focus ▪ Accurate identification of individuals at risk of dementia or with predementia is important for clinical trial enrolment. ▪ Diagnosis of predementia is usually made using the amnestic form of Mild Cognitive Impairment (aMCI). While specific criteria for implementation exist, there is no operationalisation protocol. ▪ Research Question: How have criteria for aMCI been operationalised in randomised controlled clinical trials? Key messages ▪ Various methods have been applied for operatio- nalising aMCI criteria in randomised controlled clinical trials resulting in variability in participant selection. ▪ The results highlight the urgent need for a stan- dardised approach to map aMCI. ▪ Lack of specific methods for clinical diagnosis is not a problem unique to the field of MCI. Across studies there continues to be inconsistency in the instruments and methodology used to diag- nose Alzheimer’s disease and Vascular Dementia, including its prodromal stage, Vascular Cognitive Impairment no Dementia. Revision of diagnostic criteria should be a research priority. Strengths and limitations of this study ▪ The review focuses on predementia defined using aMCI. However, not all clinical trials on predementia cognitive states have used this def- inition of MCI. ▪ We chose to focus on aMCI as this is one of the commonly applied definitions in clinical and research practice. Christa Maree Stephan B, Minett T, Pagett E, et al. BMJ Open 2013;3:e001909. doi:10.1136/bmjopen-2012-001909 1 Open Access Research