Reduction of hippocampal hyperactivity improves cognition in amnestic mild cognitive impairment
Arnold Bakker, Gregory L Krauss, Marilyn S Albert, Caroline L Speck, Lauren R Jones, Craig E Stark, Michael A Yassa, Susan S Bassett, Amy L Shelton, Michela Gallagher, Arnold Bakker, Gregory L Krauss, Marilyn S Albert, Caroline L Speck, Lauren R Jones, Craig E Stark, Michael A Yassa, Susan S Bassett, Amy L Shelton, Michela Gallagher
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.
Copyright © 2012 Elsevier Inc. All rights reserved.
Figures
![Figure 1. Task designed to tax hippocampal…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3351697/bin/nihms369300f1.jpg)
![Figure 2. Levetiracetam treatment normalizes increased dentate…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3351697/bin/nihms369300f2.jpg)
Figure 3. Levetiracetam treatment improves task-related memory…
Figure 3. Levetiracetam treatment improves task-related memory performance on critical lure items in patients with…
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- Randomized Controlled Trial
- Research Support, N.I.H., Extramural
- Aged
- Aged, 80 and over
- Amnesia / complications
- Brain Mapping
- Case-Control Studies
- Choice Behavior / drug effects
- Cognitive Dysfunction / drug therapy*
- Cognitive Dysfunction / etiology
- Cognitive Dysfunction / pathology*
- Double-Blind Method
- Female
- Hippocampus / blood supply
- Hippocampus / drug effects*
- Hippocampus / physiopathology*
- Humans
- Image Processing, Computer-Assisted
- Levetiracetam
- Magnetic Resonance Imaging
- Male
- Middle Aged
- Neuropsychological Tests
- Nootropic Agents / therapeutic use*
- Oxygen / blood
- Photic Stimulation
- Piracetam / analogs & derivatives*
- Piracetam / therapeutic use
- Statistics as Topic
- Nootropic Agents
- Levetiracetam
- Oxygen
- Piracetam
- Full Text Sources
- Other Literature Sources
- Medical
- Miscellaneous
![Figure 3. Levetiracetam treatment improves task-related memory…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3351697/bin/nihms369300f3.jpg)
Source: PubMed