Age and Ageing Advance Access originally published online on September 19, 2007
Age and Ageing 2007 36(6):685-686; doi:10.1093/ageing/afm112
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Addenbrooke's Cognitive Examination-Revised (ACE-R) in day-to-day clinical practice
The diagnostic accuracy of Addenbrookes Cognitive Examination (ACE) as a brief ‘bedside’ cognitive screening instrument [1] has led to its widespread adoption. Nonetheless, certain weaknesses have been identified in the ACE, prompting the development of the Addenbrooke's Cognitive Examination-Revised (ACE-R) [2]. The ACE-R has been reported to have excellent sensitivities and specificities (>0.8) for the diagnosis of dementia at cut-off scores of 88/100 and 82/100 in the setting of a university hospital clinic [2]. However, the question remains as to how ACE-R might fare in a pragmatic study which reflects day-to-day clinical practice. A prospective study of ACE-R in consecutive new referrals to the Cognitive Function Clinic was undertaken, following the principles of previous studies of the ACE in this setting [3]. As this was an audit of practice, institutional ethical committee approval was not sought.Of 100 patients seen (M:F = 51:49; age range 24–85 years, mean age = 60.9 ± 11.6 years), 46 were diagnosed with dementia, due to Alzheimer's disease (AD; n = 33), frontotemporal dementia (8), vascular dementia (2), dementia with Lewy bodies (1), and other causes (2). Working diagnoses in the non-demented group were mild cognitive impairment (18), affective disorder (10), and ‘purely subjective memory impairment’ (25); one patient was thought to be malingering. The frequencies of demented versus non-demented and of the differential diagnoses of dementia were similar to those seen in previous cohorts from this clinic.
ACE-R was completed, in around 10–15 minutes, by 99 patients. The one exception was a patient with profound amnesia and visual agnosia due to autosomal dominant AD owing to a presenilin-1 mutation [4].
Applying the principles of evidence-based diagnosis [5], various parameters were calculated from clinical diagnoses and ACE-R scores at cutoffs of 88 and 82 (Table 1). These showed excellent sensitivity (>0.95), commensurate with the index paper, and hence large negative likelihood ratios (<0.1), but much poorer specificity (<0.75) and hence unimportant (1–2) or small (2–5) positive likelihood ratios. Positive predictive values (PPV) were modest (<0.8).
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Because of the relatively unselected nature of this cohort, and specifically the absence of a normal control group (all patients had at least a complaint of impaired cognition, usually of memory, hence their referral), a lower cut-off value (75/100) was also examined [3]. This showed improved specificity (>0.9) without seriously comprising sensitivity (>0.9). Moreover, PPV approached 0.9, the negative likelihood ratio remained large (<0.1), and positive likelihood ratio was now on the moderate/large threshold (=10).
Receiver operating characteristic (ROC) curve was constructed (not shown), with area under the curve (AUC) of 0.95 (95% CI = 0.90–0.99), indicating excellent diagnostic accuracy (AUC = 0.5 indicates a test providing no added information, AUC = 1 indicates a test providing perfect discrimination).
This study reflects clinical practice in that there was no selection of patients by disease category, no application of exclusion criteria, and no control group of normal individuals. It showed ACE-R to have high patient acceptability and excellent diagnostic accuracy for dementia. It confirmed the findings of better sensitivity but lower PPV at higher cut-off values as reported in the index study [2]. However, using these cutoffs specificity was poor, and although negative likelihood ratios indicated large diagnostic gain (for the exclusion of dementia) positive likelihood ratios were at best small. Since no exclusion criteria were applied in the selection of this cohort (i.e. there was no selection bias other than referral bias), and there was no normal control group, the casemix was perhaps different from that in the index paper, and hence it was thought justifiable to examine a lower cut-off value (75/100). This improved specificity and positive likelihood ratio (for the diagnosis of dementia). As in the index paper, the effect of education on ACE-R was not examined in this study; age was found to have relatively little effect [2].
Hence, this pragmatic study confirms the diagnostic accuracy of the ACE-R and demonstrates its utility in day-to-day clinical practice, but suggests that lower cutoffs than those indicated in the index paper may be necessary to optimise diagnostic gain.
- ACE-R is easy to use and patient acceptable.
- ACE-R has excellent sensitivity.
- Test specificity and positive predictive value may be improved by using lower cutoffs.
- ACE-R has excellent diagnostic accuracy (area under ROC curve).
Acknowledgements
No financial disclosures or conflict of interest.
Cognitive Function Clinic, Walton Centre for Neurology and Neurosurgery, Lower Lane, Fazakerley, Liverpool L9 7LJ, UK
Email: a.larner{at}thewaltoncentre.nhs.uk
References
- Mathuranath PS, Nestor PJ, Berrios GE, et al. A brief cognitive test battery to differentiate Alzheimer's disease and frontotemporal dementia. Neurology (2000) 55:1613–20.
[Abstract/Free Full Text] - Mioshi E, Dawson K, Mitchell J, et al. The Addenbrooke's Cognitive Examination Revised (ACE-R): a brief cognitive test battery for dementia screening. Int J Geriatr Psychiatry (2006) 21:1078–85.[CrossRef][Web of Science][Medline]
- Larner AJ. An audit of the Addenbrooke's Cognitive Examination (ACE) in clinical practice. 2. Longitudinal change. Int J Geriatr Psychiatry (2006) 21:698–9.[CrossRef][Web of Science][Medline]
- Larner AJ, Ray PS, Doran M. The R269H mutation in presenilin-1 presenting as late-onset autosomal dominant Alzheimer's disease. J Neurol Sci (2007) 252:173–6.[CrossRef][Web of Science][Medline]
- Qizilbash N. Evidence-based diagnosis. In: Evidence-Based Dementia Practice—Qizilbash N, Schneider LS, Chui H, et al, eds. (2002) Oxford: Blackwell. 18–25.
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  H. J. Woodford and J. George Addenbrooke's Cognitive Examination - Revised in day-to-day clinical practice Age Ageing, May 1, 2008; 37(3): 350 - 350. [Full Text] [PDF]
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