A novel computerized cognitive test for the detection of MCI and its association with neurodegeneration in Alzheimer’s disease prone brain regions

Abstract During the prodromal stage of Alzheimer’s disease (AD), neurodegenerative changes can be identified by measuring volumetric loss in AD-prone brain regions on MRI. Cognitive assessments sensitive enough to measure the early brain-behavior manifestations of AD and correlate with biomarkers of neurodegeneration are needed to identify and monitor individuals at risk for dementia. Weak sensitivity to early cognitive change has been one major limitation of traditionally used assessment tools. In this study, we focused on expanding our previous work by determining 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. A second focus was to correlate LASSI-BC performance to volumetric reductions in AD-prone regions. Data was gathered from 127 older adults who were comprehensively evaluated and administered the LASSI-BC. Eighty-seven of these participants (51 CU; 36 aMCI) underwent MRI imaging. The volumes of 12 AD-prone brain regions were related to LASSI-BC and other memory indices correcting for False Discovery Rate (FDR). Results indicated that, even after adjusting for initial learning ability, the failure to recover from proactive semantic interference (frPSI) on the LASSI-BC differentiated between CU and aMCI groups. An optimal combination of frPSI and initial learning strength on the LASSI-BC yielded an area under the ROC curve of .876 (76.1% sensitivity, 82.7% specificity). Further, LASSI-BC measures of frPSI were associated with volumetric reductions in AD prone regions including the hippocampus, amygdala, inferior temporal lobes, precuneus and posterior cingulate.