The authors of this study have observed that patients with amnestic mild cognitive impairment (aMCI) show increased fMRI activation in the dentate gyrus/CA3 region of the hippocampus compared to controls. Elevated hippocampal activation has been previously observed in conditions that confer risk for Alzheimer’s disease. Animal studies have indicated that overactivity of specific hippocampal circuits contributes to cognitive impairment. The authors used the antiepileptic drug levetiracetam (125 mg BID) to reduce hippocampal activation in aMCI subjects to levels that did not differ from control subjects. This low-dose levetiracetam was observed to improve task-related memory performance in aMCI subjects (compared to their memory performance under placebo). Contrary to the view that greater hippocampal activation might serve a beneficial function, these results support the view that increased hippocampal activation in aMCI is a dysfunctional condition and that targeting excess hippocampal activity has therapeutic potential in amnestic MCI.
Bakker A, Krauss GL, Albert MS, Speck CL, Jones LR, Stark CE, Yassa MA, Bassett SS, Shelton AL, Gallagher M: Reduction of hippocampal hyperactivity improves cognition in amnestic mild cognitive impairment. Neuron 74(3): 467-474 (2012).