Relationships between fine memory discrimination and tau burden in two independent cohorts of older adults

Cognitive assessments sensitive to the integrity of the medial temporal lobe, an area vulnerable to early tau deposition, may serve as low-cost adjunctive markers of underlying tau pathology in older adults. The Mnemonic Similarity Task (MST) is a fine memory discrimination task designed to assess hippocampal integrity. The current cross-sectional study utilized baseline data from two AD prevention trials (the Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) study and the Exercise in Adults with Mild Memory Problems (EXERT) trial) to examine relationships between MST performance, amyloid-beta, tau, and hippocampal volume. We additionally explored relationships between performance on a traditional memory test, Logical Memory, and AD-related brain measures. Poorer fine memory discrimination was associated with higher tau as assessed by PET in A4 (N = 407, 59% female, mean age = 71.66, age range = 65-85) and CSF (p-tau181, total tau) in EXERT (N = 41, 61% female, mean age = 74.10, age range = 65-89). Poorer fine memory discrimination was also associated with higher amyloid PET in A4 and smaller hippocampal volume in EXERT. Poorer delayed recall on Logical Memory was associated with higher tau and amyloid burden in A4 and with lower hippocampal volume in EXERT. Poorer retention on Logical Memory was associated with higher tau in Braak I and amyloid in A4 and with CSF tau and lower hippocampal volume in EXERT. These results support the potential of fine memory discrimination as measured by the MST as an adjunctive, accessible screening measure associated with higher tau in cognitively normal, amyloid positive older adults and older adults with amnestic MCI.