Behavioral and Electrophysiological Correlates of Memory Binding Deficits in Patients at Different Risk Levels for Alzheimer's Disease

Abstract

Deficits in visual short-term memory (VSTM) binding have been proposed as an early and specific marker for Alzheimer?s disease (AD). However, no studies have explored the neural correlates of this domain in clinical categories involving different risk levels of conversion to AD. To bridge such a gap, we assessed underlying electrophysiological modulations in patients with mild cognitive impairment (MCI), patients in the MCI stages of familial AD carrying the mutation E280A of the presenilin-1 gene (MCI-FAD), and healthy controls. Moreover, we compared the behavioral performance of both patient groups. Participants completed a change-detection VSTM task assessing recognition of changes between shapes or shape-color bindings, presented in two consecutive arrays (i.e., study and test). Changes always occurred in the test array and consisted of new features replacing studied features (shape only) or features swapping across items (shape-color binding). Both MCI and MCI-FAD patients performed worse than controls in the shape-color binding condition. Moreover, multi-domain MCI patients were outperformed by pure amnestic and non-amnestic MCI patients. Early electrophysiological activity (100-250 ms) was significantly reduced in both clinical groups, particularly over fronto-central and parieto-occipital regions. However, shape-color binding performance was similar between MCI and MCI-FAD. Our results support the validity of the VSTM binding test in the early detection of AD and highlight the importance of studies comparing samples at different risk for AD conversion.