Abstract

The definition of test cut-offs is a critical determinant of many paired and unitary measures of diagnostic or screening test accuracy, such as sensitivity and specificity, positive and negative predictive values, and correct classification accuracy. Revision of test cut-offs from those defined in index studies is frowned upon as a potential source of bias, seemingly accepting any biases present in the index study, for example related to sample bias. Data from a large pragmatic test accuracy study examining the Mini-Addenbrooke’s Cognitive Examination (MACE) were interrogated to determine optimal test cut-offs for the diagnosis of dementia and mild cognitive impairment (MCI) using either the maximal Youden index or the maximal correct classification accuracy. Receiver operating characteristic (ROC) and precision recall (PR) curves for dementia and MCI were also plotted, and MACE predictive values across a range of disease prevalences were calculated. Optimal cut-offs were found to be a point lower than those defined in the index study. MACE had good metrics for the area under the ROC curve and for the effect size (Cohen’s d) for both dementia and MCI diagnosis, but PR curves suggested the superiority for MCI diagnosis. MACE had high negative predictive value at all prevalences, suggesting that a MACE test score above either cut-off excludes dementia and MCI in any setting.

Highlights

  • The Mini-Addenbrooke’s Cognitive Examination (MACE) is a shortened version of the Addenbrooke’s Cognitive Examination-Revised (ACE-R) and ACE-III developed by Mokken scaling analysis of these longer instruments [1]

  • Whom were diagnosed with dementia

  • Examination suggested that the optimal test cut-offs differ slightly from those suggested in the index study, being a point lower for both high-sensitivity (≤24/30 vs. ≤25/30) and high-specificity (≤20/30 vs. ≤21/30) cut-offs

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Summary

Introduction

The Mini-Addenbrooke’s Cognitive Examination (MACE) is a shortened version of the Addenbrooke’s Cognitive Examination-Revised (ACE-R) and ACE-III developed by Mokken scaling analysis of these longer instruments [1]. In the index MACE study, two cut-off points were identified in the cohort examined 82, corticobasal syndrome 21, controls 78): ≤25/30 had high sensitivity (0.85) and high specificity (0.87); and ≤21/30 had high specificity (1.00), and an abnormal score was almost certain to have come from a dementia patient. The general applicability of these MACE cut-offs for the diagnosis of dementia and mild cognitive impairment (MCI) has not been widely examined. A Spanish translation administered to a cohort of mixed dementia patients and controls (n = 175) with relatively low educational experience found that a cut-off between 16/30 and 17/30 had optimal sensitivity (0.867) and specificity (0.870) for dementia diagnosis [2]

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