Free and Cued Selective Reminding Test sensitivity

We read with great interest the recent article by Teichmann et al. [1], who presented results of the Free and Cued Selective Reminding Test (FCSRT) accuracy to differentiate typical (amnestic) Alzheimer’s disease (AD) from other neurodegenerative diseases. The authors assessed FCSRT in a group of 992 individuals, most of them with the diagnosis of AD, and stated that FCSRT would have a sensitivity of 100% and a specificity of 75% to diagnose typical AD. A diagnostic test for amnestic variant of AD that is very sensitive and specific in early stages of dementia would be extremely useful to distinguish it more accurately from other neurodegenerative diseases, especially in the context of possible disease-modifying therapy, probably effective in early or prodromic phases. FCSRT has been suggested by the International Working Group as a test to characterize amnestic syndrome of hippocampal type [2] and in fact has been demonstrating high correlation with AD pathology [3] and high sensitivity to predict mild cognitive impairment conversion to dementia [4]. However, we consider that the methods used to analyze the test performance introduced some bias to the results. The authors stated, in the methods section, that FCSRT was used to select patients to enter the study, rather than other test or set of tests, that would diagnose a patient as having amnestic variant of AD; that is, all patients with amnestic hippocampal syndrome were selected by the same instrument that is in fact being tested. Indeed, the sensitivity described in table 1 was 100%, both for AD dementia as for prodromal AD. The use of biomarkers for AD does not help in the mitigation of this bias, as this simply implies that patients included in the study had most likely AD pathology. Both the sensitivity and specificity of a test must be established regardless of the means for which the true diagnosis was established. In other words, the diagnostic test being evaluated should not be a part of the information used to establish the diagnosis [5]. Because there is no gold standard test for the presence of hippocampal amnestic deficits, it would be more useful to compare FCSRT with a larger