Diagnostic accuracy of a two-cut-off approach using the FAQ/MMSE ratio and FAQ for clinical preselection of patients for anti-amyloid therapy

Background Anti-amyloid therapies for Alzheimer’s disease (AD) require efficient patient selection. The Clinical Dementia Rating (CDR) scale is the reference standard for staging, but it is time-consuming to administer. Simple tools to distinguish early-stage cognitive impairment (CDR 0.5–1) from more advanced stages (CDR 2–3) would therefore be of substantial clinical value. Methods Participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohorts 1–3 with CDR ≥0.5 were analysed. Three logistic regression models using Mini–Mental State Examination (MMSE), Functional Assessment Questionnaire (FAQ) or the FAQ/MMSE ratio as predictors were developed. Two cut-offs per model were selected to ensure minimum sensitivity and specificity of 0.99, defining rule-out, rule-in and intermediate (uncertain) zones. Performance was assessed using discrimination, calibration and decision curve analysis. Results Among 1533 ADNI participants with CDR ≥0.5, two-thirds (n=1022) were assigned to the training set and one-third (n=511) to the test set. FAQ/MMSE and FAQ showed excellent discrimination (area under the curve, AUC 0.97–0.98), outperforming MMSE (AUC 0.94–0.95). FAQ/MMSE demonstrated the best overall performance, although differences compared with FAQ were small and not statistically significant. Dual cut-offs for FAQ/MMSE (0.67 and 1.44) and FAQ (12 and 27) enabled clinically meaningful stratification, with 80% and 70% of participants classified into high-confidence zones, respectively. Results were consistent across the training and test sets. Conclusions The FAQ/MMSE ratio and FAQ score show high accuracy in distinguishing early-stage (CDR 0.5–1) from more advanced cognitive impairment (CDR 2–3). These simple measures may support the clinical preselection of patients for further evaluation in the context of anti-amyloid therapy.