Semantic Intrusion Errors Differentiate Between Amnestic MCI who are Plasma p-tau217+ From p-tau217-After Adjusting for Initial Learning Strength

Rosie E Curiel^1*David Vaillancourt²Alexandra Ortega¹Elizabeth A Crocco¹Kirsten Crenshaw¹Stephanie M Remedios¹Breton Michael Asken³Melissa Armstrong⁴Idaly V Uribe⁵Wei-en Wang²Monica Rosselli⁶Malek Adjouadi⁷Michael Marsiske³Warren Barker⁵Steven DeKosky⁸Glenn Smith³Ranjan Duara⁵David A. Loewenstein¹

• ¹Center for Cognitive Neuroscience and Aging, Leonard M. Miller School of Medicine, University of Miami, Miami, Florida, United States
• ²Department of Applied Physiology and Kinesiology, College of Health and Human Performance, University of Florida, Gainesville, Florida, United States
• ³Department of Clinical and Health Psychology, College of Public Health and Health Professions, University of Florida, Gainesville, Florida, United States
• ⁴Department of Neurology, College of Medicine, University of Florida, Gainesville, Florida, United States
• ⁵Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami, United States
• ⁶Department of Psychology, Charles E. Schmidt College of Science, Florida Atlantic University, Boca Raton, Florida, United States
• ⁷Center for Advanced Technology and Education, College of Engineering and Computing, Florida International University, Miami, Florida, United States
• ⁸McKnight Brain Institute, J. Crayton Pruitt Family Department of Biomedical Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, Florida, United States

Background: Semantic intrusion errors (SIEs) are associated with Mild Cognitive Impairment (MCI) due to Alzheimer's Disease (AD). It is unknown whether accounting for maximum learning capacity still leads to an increase in SIEs when elevated plasma p-tau217, a biological indicator of underlying AD, is present.Methods: One hundred fifty-eight older adult participants completed the LASSI-L, a sensitive cognitive challenge test designed to elicit SIEs. Of these, 108 were clinically diagnosed with amnestic MCI (aMCI). Fifty-eight individuals met or exceeded a plasma p-tau217 positivity of >.55 pg/ml, while 50 individuals scored below this threshold.Results: After adjusting for demographic covariates and maximum learning capacity, the aMCI p-tau217+ group evidenced more SIEs compared to aMCI p-tau217-on the first (List B1; p=.035) and second trials of the competing list (List B2; p=.006). Biological predictors such as ApoE ɛ4 status, higher p-tau217, and older age were predictors of an elevated number of SIEs [List B2: F (3,104) = 10.92; p=.001; R=.489)].Unlike previous studies that used amyloid PET or other plasma biomarkers, individuals with aMCI p-tau217+ evidenced more SIEs, even after adjusting for their initial learning capacity, a covariate that has not been studied previously. These findings support that SIEs are more prevalent in the presence of underlying AD pathology and occur independent of learning deficits.