The neural correlates of verbal short-term memory in Alzheimer's disease: an fMRI study.

Although many studies have shown diminished performance in verbal short-term memory tasks in Alzheimer's disease, few studies have explored the neural correlates of impaired verbal short-term memory in Alzheimer's disease patients. In this fMRI study, we examined alterations in brain activation patterns during a verbal short-term memory recognition task, by differentiating encoding and retrieval phases. Sixteen mild Alzheimer's disease patients and 16 elderly controls were presented with lists of four words followed, after a few seconds, by a probe word. Participants had to judge whether the probe matched one of the items of the memory list. In both groups, the short-term memory task elicited a distributed fronto-parieto-temporal activation that encompassed bilateral inferior frontal, insular, supplementary motor, precentral and postcentral areas, consistent with previous studies of verbal short-term memory in young subjects. Most notably, Alzheimer's disease patients showed reduced activation in several regions during the encoding phase, including the bilateral middle frontal and the left inferior frontal gyri (associated with executive control processes) as well as the transverse temporal gyri (associated with phonological processing). During the recognition phase, we found decreased activation in the left supramarginal gyrus and the right middle frontal gyrus in Alzheimer's disease patients compared with healthy seniors, possibly related to deficits in manipulation and decision processes for phonological information. At the same time, Alzheimer's disease patients showed increased activation in several brain areas, including the left parahippocampus and hippocampus, suggesting that Alzheimer's disease patients may recruit alternative recognition mechanisms when performing a short-term memory task. Overall, our results indicate that Alzheimer's disease patients show differences in the functional networks underlying memory over short delays, mostly in brain areas known to support phonological processing or executive functioning.