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Review

Addenbrooke’s cognitive examination III in the diagnosis of dementia: a critical review

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Pages 441-447 | Published online: 15 Feb 2019

Abstract

Addenbrooke’s cognitive examination III is a screening test that is composed of tests of attention, orientation, memory, language, visual perceptual and visuospatial skills. It is useful in the detection of cognitive impairment, especially in the detection of Alzheimer’s disease and fronto-temporal dementia. The aim of this study is to do a critical review of the Addenbrooke’s cognitive examination III. The different language versions available and research about the different variables that have relationship with the performance of the subject in the ACE-III are listed. The ACE-III is a detection technique that can differentiate patients with and without cognitive impairment, is sensitive to the early stages of dementia, and is available in different languages. However, further research is needed to obtain optimal cutoffs for the different versions and to evaluate the impact of different age, gender, IQ, and education variables on the performance of the test.

Introduction

The Addenbrooke’s cognitive examination (ACE) was developed by Hodges et al as an extended cognitive screening technique, designed to detect dementia and differentiate Alzheimer dementia from fronto-temporal dementia.Citation1 It was also developed to overcome the neuropsychological omissions present in the Mini Mental State Examination (MMSE).Citation2 The aim of ACE was to be a screening technique that evaluates the principal cognitive functions and grants free access to health professionals.Citation3 In this way, ACE turns into a brief cognitive screening tool, which takes 15–20 minutes to administer and is useful in the detection of dementia syndromes.Citation4

The ACE is composed of tests of attention, orientation, memory, language, visual perception and visuospatial skills.Citation3 All of these measures have significant correlations with the classical neuropsychological tests.Citation4

The aim of this study is to critically review the Addenbrooke’s cognitive examination III.

Description of ACE-III

The ACE-III was developed to remove the MMSE elements from the ACE and ACE-R, as the MMSE was no longer open access in the year 2001.Citation5 Because of this, recent guidelines have provided alternatives to the MMSE, and the ACE-III has been recommended by the Department of Health and the Alzheimer’s Society in the UK.Citation6 In this way, the MMSE items present in the ACE-R were substituted for by similar items.Citation1 For example, in the attention section the spelling of the word “WORLD” backwards was omitted, leaving only the subtraction of serial 7s. In the language section, the written command “close your eyes” was omitted, the denomination of a pencil and clock was replaced by a book and a spoon, and the three-step command was replaced by three single-step commands, due to the lack of sensitivity to cognitive impairment.Citation1,Citation4 Finally, in the same section, the writing of a single sentence was replaced by writing two or more sentences. In the visuospatial section, the intersecting pentagons were replaced with intersecting lemnisci.Citation3 Hence, with these changes the administration of the ACE-III makes scoring the MMSE void.Citation4 As the ACE-III is designed to address the weakness of the ACE-R, the verbal repetition item was modified due to the poor performance of this item in healthy adults.Citation3

As previously described, the ACE-III is composed of five cognitive domains, attention, memory, language, verbal fluency, and visuospatial abilities. The ACE-III takes ~20 minutes to complete (). Similarly to the ACE-R, the total score of the ACE-III is based on a maximum score of 100, with higher scores indicating better cognitive functioning.

Table 1 Cognitive domain, tasks, and sub-total score of ACE-III

The index study of the ACE-III demonstrated high sensitivity and specificity, with cutoffs recommended as for the ACE-R as follows: 1) 88 (sensitivity =1.0; specificity =0.96) and 2) 82 (sensitivity =0.93; specificity =1.0).Citation4

Correlation of ACE-III with neuropsychological tests

It has been demonstrated that the subtests of the ACE-III have significant correlations with neuropsychological tests in that domain. The memory domain of the ACE correlated with two classical neuropsychological tests of memory, Free and Cued Selective Reminding Test and the Rey Auditory Verbal Learning Test.Citation4,Citation7 The language domain correlated with the Boston Naming Test, the attention domain correlated with tests that evaluate attention and executive functions (the trail making test, memory span, Stroop test), and the fluency scores correlated with executive functions.Citation7 Therefore, the administration of this screening technique quickly provides the clinician with a neuropsychological profile.

The cutoff points of ACE-III show strong correlations with the cutoff points of the ACE-R,Citation4 suggesting that this screening technique is capable of differentiating patients with and without cognitive impairment, and mild cognitive impairment (MCI).Citation3 In addition, the ACE-III performance has broader clinical implications in that it relates to carer reports of functional impairment in most common dementias.Citation8

Comparison of the ACE-III with other screening techniques

In different studies that compare the ability to discriminate healthy people and people with dementia, the ACE-III showed similar results to other screening techniquesCitation9 (MoCACitation10 and RUDASCitation11).

Like the other screening techniques (MMSE, MOCA, RUDAS), the ACE-III provides the clinician with a quick and brief global cognitive screen of the patient specifying both the overall cognitive profile and measures of each of the evaluated domains.Citation9,Citation10 In this way, ACE-III provides the clinician with a more comprehensive assessment view of the cognitive profile of the patient, helping to provide a differential diagnosis.Citation12 Moreover, as the ACE-III includes different scores for each domain, in addition of the general score, it allows for tracking the progression of cognitive deficits over time.Citation13

The MMSE lacks sensitivity to identify fronto-temporal dementias, whereas the ACE-III had demonstrated accuracy for detecting fronto-temporal dementia.Citation4 An important limitation of the MMSE is the lack of sensitivity for the early stages of dementia,Citation14 whereas the ACE-III had demonstrated accuracy in detecting MCI. The ACE-III showed better sensitivity for detecting dementia compared to the MMSE.Citation15 The ACE-III more efficiently identifies everyday functional impairments compared with both the MMSE and MoCA.Citation16

Despite the above considerations, the MMSE continues to be the preferred screening instrument for many neurologists. For this reason, a conversion table between ACE-III and MMSE has been developed and is used for clinical and research purposes.Citation17

In addition, a study by Larner investigated the relationship between administration time and diagnostic accuracy in cognitive screening tests. The author reports positive correlations between the accuracy and time of administration of the test and significant correlations between the accuracy and the number of items included in the test. These observations suggest that tests with more items (ie, longer tests) are more accurate.Citation18 The number of items of the MMSE is 30 compared with the ACE-III, which have 100 items.

Utility of the ACE-III in the detection of cognitive impairment

Dementia has been declared a global challenge, causes a great burden for the families of the patients, and leads to enormous global annual costs, which are expected to increase significantly in the next few decades.Citation20Citation22 Although several risk factors are implicated, the principal risk factor is age, and wit aging and growing populations dementia is becoming more prevalent.Citation22 Therefore, it is essential that a sensitive and specific screening tool that not only identifies patients with dementia but also identifies them in the early stages of the disease will be widely used to allow earlier diagnosis and intervention and to postpone dementia.Citation23

MCI

MCI is the prodromal phase associated with brain disorders, including of Alzheimer’s disease,Citation24 Parkinson’s disease,Citation25 cerebrovascular disease,Citation26 and fronto-temporal dementia.Citation27

The ACE-III has shown high diagnostic accuracy for MCI, being the memory domain the most sensitive in early stages of Alzheimer’s disease patients.Citation7 Moreover, the ACE-III has demonstrated high diagnostic accuracy in individuals with subjective cognitive impairment.Citation28

Dementia

The ACE-III, like its predecessors, was designed for the detection of dementias in early stages.Citation3 Good levels of sensitivity have been reported in the distinction between healthy controls and patients with some type of dementia in initial stages.Citation4,Citation7

Research reports that ACE-III is one of the most sensitive screening tools for the detection of dementia, compared to other screening tests such as MMSE and MOCA.Citation3 It has been reported that a cutoff point of 61 on the ACE-III is sensitive for distinguishing mild dementia from moderate dementia.Citation16

Considering that the ACE-III has properties similar to that of its predecessors, it can be considered to be a useful instrument for longitudinal follow-ups as its predecessors.Citation29,Citation30

In addition, the value of ACE-III for discriminating between Alzheimer’s dementia and fronto-temporal dementia has been reported.Citation4,Citation7,Citation28,Citation31 Patients with Alzheimer dementia and fronto-temporal dementia showed significant differences in the performance on the different components of the ACE: orientation, attention, and memory were worse in Alzheimer patients, while the fluency with letters, language, and names were worse in patients with fronto-temporal dementia. Mathuranath, using the ACE and the ACE-R,Citation1,Citation3 translated this scoring pattern into an index that is considered useful for the differentiation of both types of dementia (the VLOM ratio). Many different researchers have shown the usefulness of the new version of the ACE.Citation4,Citation7,Citation28,Citation31

On the other hand, the usefulness of the annualized change rates (ARC) in the total ACE scores was reported. This can be calculated using the total score in the previous and current ACE and the number of months between both evaluations, according to this formula: ARC of ACE = [(last ACE score-baseline ACE score)/(months between evaluation)] × 12.Citation29,Citation30

Stroke

Stroke can involve physical and cognitive impairments. To the best of our knowledge, there is only one study that studied the utility of the ACE-III in the detection of cognitive impairment after stroke.Citation19 As an advantage, the ACE-III not only provides the clinician with a cutoff point but also shows an estimated cognitive profile of the patient.Citation7 In this way, it provides the clinician with useful information about the cognitive functions of the patient. Moreover, the application of a screening tool can accelerate the diagnostic process of cognitive deficit after stroke and implementing cognitive rehabilitation.Citation32

It is fundamental when interpreting the cutoff points after stroke to understand that because many of the subtests of the ACE-III cannot be evaluated. In this way, the vast majority of patients after stroke score below the cutoff point.Citation19 This is due to the fact that many patients after the stroke typically present with motor difficulties, which negatively impacts the motor output subtests (example: drawing) and often have difficulties in the with language, many times because they present with aphasia.Citation33

Parkinson

Currently, there are no studies that have studied the accuracy of ACE-III in the seeking of cognitive impairment in Parkinson disease (PD). Nevertheless, the coping of the wire cube, present in the visuospatial domain of ACE-III, has correlated significantly with a poor performance on other cognitive domains, suggesting that is a sensitive detector of cognitive impairment in PD.Citation34

Variables to consider in the interpretation of the cutoff points

Previous studies with the ACE-R have shown that the cutoff points are influenced by sociodemographic variables.Citation35,Citation36 In several studies, with the ACE-III in several studies, the influence of demographic variables has been considered as seen to be an important variable to take into account when interpreting the suggested cutoff points and to improve diagnostic accuracy.Citation9,Citation38,Citation40,Citation44,Citation46

Years of education

The years of education are an important variable that must be taken into account in order to correctly interpret the cutoff points of the ACE III. Level of education has been observed to have an effect on the accuracy of this screening test in the diagnosis of dementiaCitation15,Citation37Citation40 and may be attributable to the presence of items dependent on the level of education or literacy,Citation40 such as the use of irregular words, phonemic verbal fluency,Citation41 naming task,Citation42 and constructional abilities.Citation43 Previous investigations have shown that the level of education has a significant impact on both the total score and the scores of the domains.Citation44,Citation45 Thus, different cut points have been proposed depending on years of educationCitation44 and correction factors have been proposed to adjust the raw scores and equivalent scores with cutoff values.Citation46

Age

It has been found that people over 75 years old score less on the ACE-R in comparison with younger people.Citation47,Citation48 Interpretation of the cognitive profile is thus limited by age, suggesting that age is an independent predictor of performance.Citation9,Citation15,Citation40 It has been shown that all sub-scores of the ACE-III were influenced by age, being orientation, repetition of three words, and serial subtraction of the less affected by this variable.Citation38 Hence, it is essential to ensure appropriate cutoff point for older age groups, because the prevalence of cognitive impairment increases with age.Citation9,Citation38

IQ

It has been suggested that the cutoff points for screening techniques should be adjusted depending on the premorbid IQ of the patient, for better sensitivity in the detection of dementia.Citation49 In previous studies, the cutoff scores of the MMSECitation50 and MOCACitation49 have been associated with premorbid IQ. Likewise, the ACE-III cutoff points were also affected by variation in premorbid IQ.Citation40 Therefore, the cutoff points must be adjusted to the premorbid IQ values to ensure correct interpretation.

Translation of different languages

Mirza et al (2017) performed a review of all the reports of translation and cultural adaptation procedures of the cognitive examination of Addenbrooke version III (ACE-III) and its predecessors.Citation51 In this review, it was reported that the first version of ACE is available in 12 languages, the revised version in 16 languages and the third version in 4 languages. Stott et al (2017) reported that only two studies evaluated the ACE-III, but in these studies the ACE-III showed very similar results to those of the ACE-R and these results could be applied equally to the ACE-R.Citation40

In , the different versions of ACE-III currently available are listed.

Table 2 Different versions of ACE-III currently available

ACE mobile

ACE mobile was designed by Newman et al (2018) to support users of the ACE-III by guiding and automating the administration, rule adherence, scoring, and reporting. The new version of the ACE-III, ACE mobile, is an iPad version. The aim is to support the clinician in capturing accurate measurement with zero measurement error. ACE mobile is very effective at reducing errors when compared with the standard paper-and-pen test. ACE mobile is currently provided as a free tool, with no restrictions for clinical use, available on iTunes.Citation52

M-ACE

The Mini-Addenbrooke’s Cognitive Examination (M-ACE) is a short version of the ACE and was developed and validated in dementia patients.Citation3,Citation53 The M-ACE consists of 5 items with a maximum score of 30. Hsieh et al (2014) identified two cutoffs: 1) ≤25/30 has both high sensitivity and specificity and 2) ≤21/30 is almost certainly a score to have come from a dementia patient regardless of the clinical setting. It has been found to be superior to the MMSE and MoCA in diagnostic utility. Although relatively good levels of sensitivity have been reported, the use of this tool should be questioned in clinical trials where high specificity and low false positive rates are more desirable.Citation18,Citation24

Conclusion

The ACE-III is a screening technique that is capable of differentiating patients with and without cognitive impairment and is sensitive to the early stages of dementia.

Unlike other screening tests (MMSE, MOCA, RUDAS), the ACE-III provides the clinician with a brief multi-component cognitive profile, since it provides specific scores for different cognitive domains: attention, memory, verbal fluency, language, and visuospatial function. It has been demonstrated that the subtests of the ACE-III have significant correlations with neuropsychological test specific for that domain.

Currently, in addition to the English version there are versions in Spanish, Italian, Chinese, Portuguese, Egyptian Arabic, and Thai.

ACE-III is influenced by demographic variables including age, education, and IQ. All of these are considered to be important variables to take into account when interpreting the suggested cutoff points in order to improve diagnostic accuracy.

Future investigations should investigate the utility of the ACE-III in other neurological and psychiatric pathologies, such as head trauma and mood disorders.

Disclosure

The authors report no conflicts of interest in this work.

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