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

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.

Aqueous extract of lavender (Lavandula angustifolia) improves the spatial performance of a rat model of Alzheimer’s disease

“…Based on the cholinergic hypothesis, AD patients may have defects in cholinergic system, which is associated with memory and learning [14] . Indeed, increasing the level of acetylcholine (ACh) in the brain may be an effective therapy for AD treatment.…”

“…Memory function is likely to be formed by numerous discrete neural networks that can be disrupted by the pathophysiological processes in AD [14] . The hippocampus, a well-known brain region involved in memory consolidation, is especially susceptible to AD.…”

Model‐free group analysis shows altered BOLD FMRI networks in dementia

“…1G1H). This default mode network has received increasing attention in recent years, including dementia studies [Buckner et al, 2005;Celone et al, 2006;Lustig et al, 2003;Rombouts et al, 2005a]. These studies suggest that activity in this network could be particularly sensitive to differentiate (early) dementia from healthy aging.…”

“…The additional modeling flexibility may result in an increased sensitivity toward the detection of signals of interest, e.g., Greicius et al successfully applied an ICA-based analysis to compare FMRI data of demented patients and healthy elderly in an a priori defined network of interest . Celone et al used group ICA by concatenating subjects' data [Calhoun et al, 2001] to study FMRI activation in AD, MCI, and healthy elderly [Celone et al, 2006]. Most applications of model-free methods to FMRI data analysis, however, have until recently been limited to the analysis of single sessions as it has not been clear how to generalize model-free approaches to the investigations of multiple subjects/multiple groups.…”

Can multi-modal neuroimaging evidence from hippocampus provide biomarkers for the progression of amnestic mild cognitive impairment?

“…The reason may be that the aMCI patients in that study were very mildly impaired based on the Clinical Dementia Rating, MMSE, and neuropsychological data, as well as performance of the fMRI memory task similar to controls. By separating the aMCI spectrum into two subgroups, the milder end and the more impaired end, Celone and colleagues demonstrated hyperactivation in the bilateral hippocampus in very mild aMCI, but hypoactivation in more impaired aMCI in an associative face-name encoding paradigm [65] .…”