Alterations in Memory Networks in Mild Cognitive Impairment and Alzheimer's Disease: An Independent Component Analysis

TLDR

Memory function is supported by distributed neural networks that are disrupted by the pathophysiological processes of Alzheimer’s disease. The study aimed to use multivariate analytic techniques to examine memory‑related fMRI activity across normal aging, mild cognitive impairment, and mild Alzheimer’s disease. Multivariate analytic techniques, specifically independent component analysis of fMRI data, were applied to 52 participants to identify memory‑related networks during an associative memory task. Independent component analysis revealed that hippocampal activation and parietal deactivation exhibit a reciprocal relationship that changes nonlinearly across the normal–MCI–AD spectrum, with less‑impaired MCI showing hippocampal hyperactivation and greater parietal deactivation, while more‑impaired MCI and mild AD display hypoactivation and loss of deactivation, accompanied by increased neocortical attentional activity, indicating that hippocampal‑based memory system dysfunction is linked to parietal network alterations and early AD pathology.

Abstract

Memory function is likely subserved by multiple distributed neural networks, which are disrupted by the pathophysiological process of Alzheimer's disease (AD). In this study, we used multivariate analytic techniques to investigate memory-related functional magnetic resonance imaging (fMRI) activity in 52 individuals across the continuum of normal aging, mild cognitive impairment (MCI), and mild AD. Independent component analyses revealed specific memory-related networks that activated or deactivated during an associative memory paradigm. Across all subjects, hippocampal activation and parietal deactivation demonstrated a strong reciprocal relationship. Furthermore, we found evidence of a nonlinear trajectory of fMRI activation across the continuum of impairment. Less impaired MCI subjects showed paradoxical hyperactivation in the hippocampus compared with controls, whereas more impaired MCI subjects demonstrated significant hypoactivation, similar to the levels observed in the mild AD subjects. We found a remarkably parallel curve in the pattern of memory-related deactivation in medial and lateral parietal regions with greater deactivation in less-impaired MCI and loss of deactivation in more impaired MCI and mild AD subjects. Interestingly, the failure of deactivation in these regions was also associated with increased positive activity in a neocortical attentional network in MCI and AD. Our findings suggest that loss of functional integrity of the hippocampal-based memory systems is directly related to alterations of neural activity in parietal regions seen over the course of MCI and AD. These data may also provide functional evidence of the interaction between neocortical and medial temporal lobe pathology in early AD.