In subjects with Mild Cognitive Impairment (MCI) memory disorders indicate a high risk for conversion to Alzheimer's disease (AD). The objective of this study was to delineate the differences in brain activation between amnestic MCI and age-matched healthy controls (HC) during a verbal working memory task. The verbal working memory task was a delay match to sample design. Brain activation was measured using functional magnetic resonance imaging. There were 8 subjects in each group and were matched for performance. The task was analyzed as an event-related design. Group differences were calculated using Analysis of Covariance (ANCOVA) with statistical significance at p < 0.05 corrected. Both groups activated a wide network in the posterior and frontal areas of the brain. There was higher activation in the parietal and frontal lobes in the MCI compared to the HC during the maintenance phase. There were no areas in the HC that activated higher than the MCI subjects. Response time in the task in the HC group was correlated to the left hippocampus during encoding phase and to the parietal and frontal areas during the recall phase. In the MCI group there was strong correlation to the inferior and middle temporal gyrii during encoding, the middle frontal gyrus during the maintenance phase, and hippocampus during recall phase. The activation differences between groups may be compensatory mechanisms within the MCI group for the effects of the putative AD neuropathology. This has been the first study that has examined verbal working memory in MCI.

Visual perception has been shown to be altered in Alzheimer disease (AD) patients, and it is associated with decreased cognitive function. Galantamine is an active cholinergic agent, which has been shown to lead to improved cognition in mild to moderate AD patients. This study examined brain activation in a group of mild AD patients after a 3-month open-label treatment with galantamine. The objective was to examine the changes in brain activation due to treatment. There were 2 tasks to visual perception. The first task was a face-matching task to test the activation along the ventral visual pathway, and the second task was a location-matching task to test neuronal function along the dorsal pathway. Brain activation was measured using functional magnetic resonance imaging. There were 5 mild AD patients in the study. There were no differences in the task performance and in the cognitive scores of the Consortium to Establish a Registry for Alzheimer's Disease battery before and after treatment. In the location-matching task, we found a statistically significant decrease in activation along the dorsal visual pathway after galantamine treatment. A previous study found that AD patients had higher activation in the location-matching task compared with healthy controls. There were no differences in activation for the face-matching task after treatment. Our data indicate that treatment with galantamine leads to more efficient visual processing of stimuli or changes the compensatory mechanism in the AD patients. A visual perception task recruiting the dorsal visual system may be useful as a biomarker of treatment effects.

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