An early fMRI marker of semantic memory deficits in people with amnestic mild cognitive impairment

Semantic memory deficits in Alzheimer's disease have often been reported. However, the nature of changes in semantic memory at pre-dementia stage is less extensively studied. By acquiring functional magnetic resonance imaging (fMRI) during a semantic memory task, we examined brain activity that could be affected by early disease processes in patients with amnestic Mild Cognitive Impairment (aMCI). We applied fMRI during the Semantic Object Retrieval Task (SORT), a task where subjects answered at each trial whether a pair of words presented would bring to mind a particular object. Trials of “Binds” probe object memory (e.g., humps and desert) whereas “NonBinds” do not (e.g., humps and mirror). We thus compared blood oxygen level dependent (BOLD) signal recorded from aMCI patients (N=6; mean age: 72.7±8.3 yr; CDR=0.5) to that of age-matched normal control (NC) subjects (N=6; mean age: 67.3±9.8 yr; CDR=0). Participants in both groups took longer to respond to NonBinds compared to Binds. No group differences in reaction time or accuracy were observed (p > .05). FMRI data showed that NC subjects demonstrated greater BOLD signal during Binds compared to NonBinds in left supramarginal gyrus and precuneus whereas no such differences were observed in the aMCI group (FWE < .05). Overall, NC subjects had greater activations than aMCI patients during Binds in bilateral medial frontal lobe, left insula, left caudate, and left post-central gyrus (p < .005, corrected at cluster size > 50 voxels), but NonBind-associated activations did not differ between groups. NC subjects had greater brain response elicited by trials that required retrieval of object memory compared to trials that did not. In contrast, aMCI patients showed no such differential brain activation while demonstrating less brain activity than NC subjects during memory retrieval. Our findings suggest that neural integrity in the regions involved in object memory retrieval is compromised in individuals with aMCI even when behavioral performance is not impaired. Presumably, changes in these brain regions indicate an early sign of semantic memory deficits that may become behaviorally measurable only at a later stage.