TMA-93 (binding by images): Cutoffs optimization based on Alzheimer's disease biomarkers

BackgroundWith the arrival of new disease-modifying treatments for Alzheimer's disease (AD), feasible cognitive tests, also for illiterate patients, are needed to screen those requiring deeper evaluation among individuals presenting with memory complaints. The TMA-93, a brief binding memory test, has proven useful for diagnosing early AD, and is supported by normative data that accounts for age and cognitive reserve.ObjectiveTo compare the sensitivity of different TMA-93 cutoffs in detecting AD pathology.MethodsA retrospective analysis was performed on a biobank sample of patients with confirmed AD pathology via amyloid PET or cerebrospinal fluid (CSF) biomarkers. The sensitivity of six TMA-93 cutoffs was evaluated: the 10th, 15th, and 20th percentiles based on traditional norming (TN) and regression-based norming (RBN). False negatives (FN) characteristics were also analyzed.ResultsA total of 270 AD-positive patients (96 by amyloid-PET, 174 by CSF biomarkers) were included, comprising 224 with mild cognitive impairment and 46 with mild dementia. The 15th percentile using RBN demonstrated substantial sensitivity (80.4%), higher than that of the 10th percentile, and also provided a more uniform distribution across normative groups compared to the TN approach. Higher global cognition (Mini-Mental State Examination score) and, in patients over 70, lower cognitive reserve (Cognitive Reserve Questionnaire), were linked to a greater likelihood of FN results.ConclusionsThe 15th percentile cutoff based on RBN, accounting for age and cognitive reserve, improves sensitivity for detecting AD pathology, making it a valuable screening tool for memory complaints. Future normative data from biomarker-negative subjects may enhance the sensitivity of cognitive tests.