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

• Published in: Journal of Alzheimer's disease Vol. 105; no. 1; pp. 65 - 76
• Main Authors: Arriola-Infante, José Enrique, García-Roldán, Ernesto, García-Solís, David, Marín-Cabañas, Alba Marta, Luque-Tirado, Andrea, Almodóvar-Sierra, Ángela, Sánchez-Arjona, María Bernal, Maillet, Didier, Franco-Macías, Emilio
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.05.2025
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - diagnosis; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - psychology; Amyloid beta-Peptides - cerebrospinal fluid; Biomarkers - cerebrospinal fluid; Cognitive Dysfunction - cerebrospinal fluid; Cognitive Dysfunction - diagnosis; Cognitive Dysfunction - diagnostic imaging; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Positron-Emission Tomography; Retrospective Studies; Sensitivity and Specificity; memory; cognition; normative data; biomarkers; cognitive reserve; neuropsychological tests; Alzheimer's disease
• ISSN: 1387-2877; 1875-8908
• DOI: 10.1177/13872877251325759

Background With 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. Objective To compare the sensitivity of different TMA-93 cutoffs in detecting AD pathology. Methods A 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. Results A 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. Conclusions The 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.