Spectrum Effect and Spectrum Bias in the Screening Test Performance for Amnestic Mild Cognitive Impairment: What are the Clinical Implications?

Background: A single cutoff is widely used to screen amnestic mild cognitive impairment (aMCI). However, results of screening test performance are never adjusted for spectrum effect and spectrum bias. Objectives: To assess the potential impact of spectrum effect and spectrum bias on screening test performance and clinical decision. Methods: The ability of the combination of Memory Impairment Screen (MIS), the Isaacs Set Test (IST), and the Mini-Mental State Examination (MMSE) to distinguish aMCI (n = 3,330) from patients with subjective cognitive complaints (SCC) (n = 1,522) was investigated across a wide range of age and educational backgrounds. The spectrum effect was defined as the variation of the sensitivity and/or the specificity across different subgroups. A spectrum bias was highlighted if the likelihood ratio (LR) observed in a subgroup of subjects statistically differed from the LR observed in the overall sample. Results: For the MIS-IST pairing, the overall sensitivity and specificity were equal to 72.5% and 75.2%, the positive LR (LR+) and the negative LR (LR-) were equal to 2.91 and 0.37, respectively. Across the different age-education subgroups, the sensitivities ranged from 43.7% to 92.5% and specificities from 39.3% to 95.2%. LR+ and LR- ranged from 1.51 to 9.10 and 0.13 to 0.59, respectively. A statistically significant spectrum bias was found in some subgroups and may result in differences between the post-test probabilities. Similar results were also found for the MMSE. Conclusion: These findings could potentially affect the clinician's decision with a possible greater impact in elderly patients with a lower educational level.