A-214 A Novel Computerized Cognitive Test for the Detection of MCI and its Association with Neurodegeneration in Alzheimer’s Disease Prone Brain Regions

Abstract Objective: First, to determine whether a digitized cognitive stress test, the Loewenstein-Acevedo Scales for Sematic Interference and Learning, Brief Computerized Version (LASSI-BC) could differentiate between Cognitively Unimpaired (CU) and amnestic Mild Cognitive Impairment (aMCI) groups. Second, to correlate LASSI-BC performance to volumetric reductions in Alzheimer’s disease (AD)-prone regions. Methods: 111 elders underwent a clinical and neuropsychological evaluation, along with the LASSI-BC. All participants were independent community-dwellers, had knowledgeable informants, and did not meet DSM-V criteria for any active neuropsychiatric disorder, Mood Disorder or Psychotic Disorder. Eighty-seven participants (51 CU; 36 aMCI) underwent MRI imaging. The volumes of 12 AD-prone regions were related to LASSI-BC and other memory indices correcting for False Discovery Rate (FDR). Results: After adjusting for initial learning ability, the failure to recover from proactive semantic interference (frPSI) of LASSI-BC successfully differentiated between groups. Measures of frPSI were associated with volumetric reductions in AD-prone regions (hippocampus, amygdala, inferior temporal-lobes, precuneus and posterior cingulate) in aMCI cohort. A combination of maximum learning capacity and frPSI on the LASSI-BC yielded an area under ROC curve of 0.876 with greater sensitivity and specificity when compared to other traditional tests (e.g., HVLT). Conclusions: Performance on the LASSI-BC successfully discriminated between diagnostic groups and is significantly associated with volumetric loss among aMCI individuals. This is significant as diagnostic cognitive tests of preclinical and prodromal AD should also be required to exhibit sensitivity to biomarkers of AD (e.g., amyloid, tau, and neurodegeneration in AD-prone regions), which may address some of the most critical challenges facing clinical trials.