Altered resting state networks in mild cognitive impairment and mild Alzheimer's disease: an fMRI study

Abstract

Activity and reactivity of the default mode network in the brain was studied using functional magnetic resonance imaging (fMRI) in 28 nondemented individuals with mild cognitive impairment (MCI), 18 patients with mild Alzheimer's disease (AD), and 41 healthy elderly controls (HC). The default mode network was interrogated by means of decreases in brain activity, termed deactivations, during a visual encoding task and during a nonspatial working memory task. Deactivation was found in the default mode network involving the anterior frontal, precuneus, and posterior cingulate cortex. MCI patients showed less deactivation than HC, but more than AD. The most pronounced differences between MCI, HC, and AD occurred in the very early phase of deactivation, reflecting the reactivity and adaptation of the network. The default mode network response in the anterior frontal cortex significantly distinguished MCI from both HC (in the medial frontal) and AD (in the anterior cingulate cortex). The response in the precuneus could only distinguish between patients and HC, not between MCI and AD. These findings may be consistent with the notion that MCI is a transitional state between healthy aging and dementia and with the proposed early changes in MCI in the posterior cingulate cortex and precuneus. These findings suggest that altered activity in the default mode network may act as an early marker for AD pathology.

Figure 1

Transverse sections with Z‐statistics of average deactivation in controls, MCI, and AD (top) during the face‐encoding task (P < 0.05, corrected). Z‐scores are color‐coded from 3.1 (red) to 6.2 (yellow). The graphs show the estimated responses with standard deviations. The underlying structural image is the average image of all controls and patients; left in image is left in the brain. MCI show less deactivation in the medial frontal gyrus than controls (middle). AD show a change in the early phase of deactivation (temporal derivative) compared to both MCI and controls (bottom) in the anterior cingulate gyrus.

Figure 2

Transverse sections with Z‐statistics of average deactivation in controls, MCI, and AD in the working memory task (P < 0.05, corrected). The underlying structural image is the average image of all controls and patients; left in image is left in the brain. MCI patients only show significant deactivation in the increased WM load condition (2BACK). AD patients only show deactivation in the 1BACK condition. Z‐scores are color‐coded from 3.1 (red) to 8.5 (yellow) for 1BACK, and from 3.1 to 9.9 for 2BACK.

Figure 3

Differences in deactivation during the working‐memory task between patients and controls. The graphs show the estimated responses with standard deviations. Differences in this task are only significant for the very early phase of the deactivation response represented by the parameter estimate of the temporal derivative. 1B = simple working memory; 2B = increased working memory load.