How accurate are the Addenbrooke's Cognitive Examination III (ACE-III) and mini-ACE for the screening of dementia and mild cognitive impairment (MCI)?

Why is recognising dementia important?

The number of people being diagnosed with dementia is expected to increase significantly over the next 10 years. There is therefore an increasing need for tools that can assess memory and learning to aid the diagnosis of dementia and MCI. The ACE-III and mini-ACE are currently used in clinical practice, but the evidence for their accuracy to identify dementia has not been fully established.

What was the aim of this review?

The aim of this review was to find out how accurate the ACE-III and mini-ACE are in identifying dementia and MCI across a range of healthcare settings. The test is performed on a patient who is suspected to have dementia.

What was studied in this review?

The ACE-III has 21 questions, with a total score of 100. The test is performed with the patient who presented with, or is suspected to have, dementia. The questions cover five different areas of brain function, and a higher score indicates better function. The mini-ACE is shorter, with only five questions, and a total score of 30. The thresholds describe the score at which a diagnosis of dementia should be considered and these are usually 82 or 88/100 for the ACE-III and 21 or 25/30 for the mini-ACE.

The ACE-III and mini-ACE are not used on their own to make a diagnosis of dementia, but help clinicians when used in addition to other clinical information and investigations.

What are the main results of the review?

This review included seven studies with a total of 1711 patients; four studies examined the ACE-III, and three examined the mini-ACE. We did not combine the study information statistically due to significant differences between the studies.

The ability of both the ACE-III and the mini-ACE to identify patients with either dementia or MCI was variable (between 70% and 99% of people were correctly identified as having dementia and between 64% and 95% for MCI). However, there was more variability between the studies in the number of false positives identified by the tests (between 0% and 96% of people were incorrectly identified as having dementia and between 8% and 54% of people were incorrectly identified as having MCI). At the lower test thresholds, there were fewer false positive diagnoses of dementia (between 64% and 100% of people correctly identified as not having dementia or MCI).

How reliable are the results of this review?

There were some issues with the methods used by studies: the way in which patients were identified and enrolled into the studies, and the way in which the ACE-III and mini-ACE were carried out were not well described. The studies were small and did not study enough people to be confident about the results. These issues mean that the accuracy of the ACE-III and mini-ACE may have appeared better than it actually was.

Who do the results of this review apply to?

The average age in all the studies was over 60 years. The proportion of people with dementia was different between studies (range: 15% to 55.6%). All of the studies were conducted in a specialist setting, so we do not know if the ACE-III or mini-ACE could be used in general practice or the community. Four studies were in the UK, two were in China, and one in Japan.

What are the implications of this review?

Overall, the quality, size, and number of included studies has not allowed a definitive conclusion on whether the ACE-III or the mini-ACE should be used to identify dementia or MCI. These findings can only be used in a hospital setting, as none of the studies investigated community or general populations. The ACE-III or mini-ACE should only be used as part of a clinical assessment when making a diagnosis of dementia, and should not be relied upon alone. More research is needed to investigate the ACE-III and mini-ACE in different healthcare settings, languages, and cultures.

How up to date is this review?

The review authors searched for and included studies up to April 2019.

Authors' conclusions: 

There is insufficient information in terms of both quality and quantity to recommend the use of either the ACE-III or mini-ACE for the screening of dementia or MCI in patients presenting with, or at high risk of, cognitive decline. No studies were conducted in a primary care setting so the accuracy of the ACE-III and mini-ACE in this setting are not known. Lower thresholds (82 for the ACE-III, and 21 for the mini-ACE) provide better specificity with acceptable sensitivity and may provide better clinical utility. The ACE-III and mini-ACE should only be used to support the diagnosis as an adjunct to a full clinical assessment. Further research is needed to determine the utility of the ACE-III and mini-ACE for the detection of dementia, dementia sub-types, and MCI. Specifically, the optimal thresholds for detection need to be determined in a variety of settings (primary care, secondary care (inpatient and outpatient), and community services), prevalences, and languages.

Read the full abstract...
Background: 

The number of new cases of dementia is projected to rise significantly over the next decade. Thus, there is a pressing need for accurate tools to detect cognitive impairment in routine clinical practice. The Addenbrooke's Cognitive Examination III (ACE-III), and the mini-ACE are brief, bedside cognitive screens that have previously reported good sensitivity and specificity. The quality and quantity of this evidence has not, however, been robustly investigated.

Objectives: 

To assess the diagnostic test accuracy of the ACE-III and mini-ACE for the detection of dementia, dementia sub-types, and mild cognitive impairment (MCI) at published thresholds in primary, secondary, and community care settings in patients presenting with, or at high risk of, cognitive decline.

Search strategy: 

We performed the search for this review on 13 February 2019. We searched MEDLINE (OvidSP), Embase (OvidSP), BIOSIS Previews (ISI Web of Knowledge), Web of Science Core Collection (ISI Web of Knowledge), PsycINFO (OvidSP), and LILACS (BIREME). We applied no language or date restrictions to the electronic searches; and to maximise sensitivity we did not use methodological filters. The search yielded 5655 records, of which 2937 remained after we removed duplicates. We identified a further four articles through PubMed 'related articles'. We found no additional records through reference list citation searching, or grey literature.

Selection criteria: 

Cross-sectional studies investigating the accuracy of the ACE-III or mini-ACE in patients presenting with, or at high risk of, cognitive decline were suitable for inclusion. We excluded case-control, delayed verification and longitudinal studies, and studies which investigated a secondary cause of dementia. We did not restrict studies by language; and we included those with pre-specified thresholds (88 and 82 for the ACE-III, and 21 or 25 for the mini-ACE).

Data collection and analysis: 

We extracted information on study and participant characteristics and used information on dementia and MCI prevalence, sensitivity, specificity, and sample size to generate 2×2 tables in Review Manager 5. We assessed methodological quality of included studies using the QUADAS-2 tool; and we assessed the quality of study reporting with the STARDdem tool.

Due to significant heterogeneity in the included studies and an insufficient number of studies, we did not perform meta-analyses.

Main results: 

This review identified seven studies (1711 participants in total) of cross-sectional design, four examining the accuracy of the ACE-III, and three of the mini-ACE. Overall, the majority of studies were at low or unclear risk of bias and applicability on quality assessment. Studies were at high risk of bias for the index test (n = 4) and reference standard (n = 2). Study reporting was variable across the included studies. No studies investigated dementia sub-types. The ACE-III had variable sensitivity across thresholds and patient populations (range for dementia at 82 and 88: 82% to 97%, n = 2; range for MCI at 88: 75% to 77%, n = 2), but with more variability in specificity (range for dementia: 4% to 77%, n = 2; range for MCI: 89% to 92%, n = 2). Similarly, sensitivity of the mini-ACE was variable (range for dementia at 21 and 25: 70% to 99%, n = 3; range for MCI at 21 and 25: 64% to 95%, n = 3) but with more variability specificity (range for dementia: 32% to 100%, n = 3; range for MCI: 46% to 79%, n = 3). We identified no studies in primary care populations: four studies were conducted in outpatient clinics, one study in an in-patient setting, and in two studies the settings were unclear.

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