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.