Detection of cerebrospinal fluid biomarkers changes of Alzheimer's disease using a cognitive stress test in persons with subjective cognitive decline and mild cognitive impairment

Introduction: Early and accurate detection of Alzheimer’s disease (AD) is crucial. The Loewenstein Acevedo Scales for Semantic Interference and Learning (LASSI-L) has demonstrated diagnostic value versus amyloid/FDG PET, but its relationship with cerebrospinal fluid (CSF) biomarkers has not been examined. We evaluated the association between LASSI-L scores and CSF biomarkers and the ability of LASSI-L to detect amyloid and tau pathology in subjective cognitive decline (SCD) and amnestic mild cognitive impairment (MCI). Methods: We enrolled 179 memory-clinic patients without functional impairment who underwent comprehensive neuropsychological testing, LASSI-L, and CSF biomarkers (Aβ1-42/Aβ1-40 ratio and p-tau181). Group comparisons, correlations, effect sizes, and ROC analyses were performed. Results: LASSI-L scores correlated significantly with CSF Aβ1-42/Aβ1-40, particularly measures of recovery from proactive semantic interference and delayed recall. A logistic regression including LASSI-L delayed recall and age achieved 0.749 accuracy and AUC 0.785 for detecting abnormal amyloid. Conclusion: Findings support the biological validity of LASSI-L and its semantic interference paradigm in early AD, highlighting the utility of sensitive cognitive challenge tests in evaluations of suspected early AD.