Trial reportNeuron2012
Reduction of hippocampal hyperactivity improves cognition in amnestic mild cognitive impairment.
Trial report in Neuron, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 555 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase 2a Levetiracetam Trial for AD-Associated Network Hyperexcitability
Network-Level Mechanisms for Preclinical Alzheimer's Disease Development
Prevalence of Epilepsy and Sleep Wake Disorders in Alzheimer Disease
Neuroimaging Epigenetics of Prospective Postpartum Depression Biomarkers
Who cites it
555 citing papers in PubMed, 3 syntheses or guidelines pooled it, 917 citations in OpenAlex.
- Effect of levetiracetam on cognition in patients with cognitive decline: A systematic review and meta-analysis of randomized controlled trials.Epilepsia open · 2025Pooled it
- Effect of Levetiracetam on Cognition: A Systematic Review and Meta-analysis of Double-Blind Randomized Placebo-Controlled Trials.CNS drugs · 2024Pooled it
- Cortical excitability and plasticity in Alzheimer's disease and mild cognitive impairment: A systematic review and meta-analysis of transcranial magnetic stimulation studies.Ageing research reviews · 2022Pooled it
- Baseline Functional Connectivity Predicts Who Will Benefit From Neuromodulation: Evidence From Primary Progressive Aphasia.Neurorehabilitation and neural repair · 2026Trial
- Safety, tolerability, and efficacy outcomes of the Investigation of Levetiracetam in Alzheimer's disease (ILiAD) study: a pilot, double-blind placebo-controlled crossover trial.Epilepsia open · 2024Trial
- Modulation of hippocampal activity in schizophrenia with levetiracetam: a randomized, double-blind, cross-over, placebo-controlled trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Trial
- Improvement of mnemonic discrimination with acute light exercise is mediated by pupil-linked arousal in healthy older adults.Neurobiology of aging · 2024Trial
- A Randomized-Controlled Trial Targeting Cognition in Early Alzheimer's Disease by Improving Sleep with Trazodone (REST).Journal of Alzheimer's disease : JAD · 2024Trial
- Trial
- Levetiracetam restores GABAergic function and network homeostasis following Vps35 deficiency in excitatory neurons.Translational neurodegeneration · 2026Article
- Characterizing hippocampal activation during pattern separation with multi-echo fMRI in cognitively normal older adults.Brain imaging and behavior · 2026Article
- Golgi dysfunction in Alzheimer disease: from human multiomic signatures to therapeutic targets.Experimental & molecular medicine · 2026Review
- Excitation-inhibition imbalance links amyloid pathophysiology to cognition in non-demented individuals.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Co-activation of Selective Nicotinic Acetylcholine Receptor Subtypes Is Required for Neuroprotection against Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Modernizing cognitive assessment in Alzheimer's disease.Nature aging · 2026Article
- Large-Scale Neural Recording Technologies for Investigating Circuit Dysfunction and Functional Biomarker Discovery in Animal Models of Alzheimer's Disease.International journal of molecular sciences · 2026Review
- Impaired spatial coding and neuronal hyperactivity in the medial entorhinal cortex of aged APP knock-in mice.Cell reports · 2026Article
- Dynamic recovery of piriform cortex function and its impact on cognitive processing speed following mild COVID-19.BMC neurology · 2026Article
- Therapeutic targeting of fibrin-microglia interactions ameliorates Alzheimer's disease-related hyperexcitability and brain network dysfunction.bioRxiv : the preprint server for biology · 2026Article
495 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.