Title | Reduction of hippocampal hyperactivity improves cognition in amnestic mild cognitive impairment. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Bakker, A, Krauss, GL, Albert, MS, Speck, CL, Jones, LR, Stark, CE, Yassa, MA, Bassett, SS, Shelton, AL, Gallagher, M |
Journal | Neuron |
Volume | 74 |
Issue | 3 |
Pagination | 467-74 |
Date Published | 2012 May 10 |
ISSN | 1097-4199 |
Keywords | Aged, Aged, 80 and over, Amnesia, Brain Mapping, Case-Control Studies, Choice Behavior, Double-Blind Method, Female, Hippocampus, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Mild Cognitive Impairment, Neuropsychological Tests, Nootropic Agents, Oxygen, Photic Stimulation, Piracetam, Statistics as Topic |
Abstract | Elevated hippocampal activation is observed in conditions that confer risk for Alzheimer's disease, including amnestic mild cognitive impairment (aMCI). Studies in relevant animal models have indicated that overactivity in selective hippocampal circuits contributes to cognitive impairment. Here, we tested the effect of reducing hippocampal activation in aMCI. Under placebo treatment, hippocampal activation in the dentate gyrus/CA3 was elevated in aMCI patients compared to a healthy control group. By using a low dose of the antiepileptic levetiracetam hippocampal activation in aMCI was reduced to a level that did not differ from the control group. Compared to aMCI memory performance under placebo, performance in the scanning task was significantly improved under drug treatment. 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. |
DOI | 10.1016/j.neuron.2012.03.023 |
Alternate Journal | Neuron |
PubMed ID | 22578498 |
PubMed Central ID | PMC3351697 |
Grant List | P50 AG005146 / AG / NIA NIH HHS / United States R01 AG034613 / AG / NIA NIH HHS / United States RC2 AG036419 / AG / NIA NIH HHS / United States RC2 AG036419-01 / AG / NIA NIH HHS / United States RC2AG036419 / AG / NIA NIH HHS / United States T32 AG027668 / AG / NIA NIH HHS / United States |
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