ArticleNeurology2010
Longitudinal fMRI in elderly reveals loss of hippocampal activation with clinical decline.
Article in Neurology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06919926 (A Randomized, Within-subject, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of AGB101), which is not on this map. Cited by 183 papers, 6 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.
A Randomized, Within-subject, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of AGB101 (Low-dose Levetiracetam, 220 mg, Extended Release Tablet) for the Treatment of Hippocampal Overactivity in the Elderly
Who cites it
183 citing papers in PubMed, 6 syntheses or guidelines pooled it, 292 citations in OpenAlex.
- Translation of task-evoked negative BOLD response into aging and Alzheimer's disease: a systematic review of the current literature.Journal of translational medicine · 2025Pooled it
- Mitochondrial dysfunction, oxidative stress, neuroinflammation, and metabolic alterations in the progression of Alzheimer's disease: A meta-analysis of in vivo magnetic resonance spectroscopy studies.Ageing research reviews · 2021Pooled it
- Understanding brain resilience in superagers: a systematic review.Neuroradiology · 2021Pooled it
- Resting State Abnormalities of the Default Mode Network in Mild Cognitive Impairment: A Systematic Review and Meta-Analysis.Journal of Alzheimer's disease : JAD · 2019Pooled it
- Potential neuroimaging biomarkers of pathologic brain changes in Mild Cognitive Impairment and Alzheimer's disease: a systematic review.BMC geriatrics · 2016Pooled it
- Specific and disease stage-dependent episodic memory-related brain activation patterns in Alzheimer's disease: a coordinate-based meta-analysis.Brain structure & function · 2015Pooled it
- Response of the medial temporal lobe network in amnestic mild cognitive impairment to therapeutic intervention assessed by fMRI and memory task performance.NeuroImage. Clinical · 2015Trial
- Chemotherapy-induced amenorrhea: a prospective study of brain activation changes and neurocognitive correlates.Brain imaging and behavior · 2013Trial
- Reduction of hippocampal hyperactivity improves cognition in amnestic mild cognitive impairment.Neuron · 2012Trial
- Before the task begins: linking resting-state gamma oscillations to face-name associative memory.Cognitive neurodynamics · 2026Article
- Characterizing hippocampal activation during pattern separation with multi-echo fMRI in cognitively normal older adults.Brain imaging and behavior · 2026Article
- Ontological Analysis of Brain Proteostasis Highlights the Sex-Dependent Trajectory of ApoE Isoform-Specific Regulation.bioRxiv : the preprint server for biology · 2026Article
- Evaluating the peripheral nervous system pathology of Alzheimer's disease utilizing a functional human NMJ microphysiological system.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- How Do Amyloid Pathology and Aberrant Neuronal Activity Disrupt Plasticity and Memory in Alzheimer's Disease?The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2026Review
- Selective weakening of population-coupled synaptic activity in vivo in a mouse model of amyloid-beta pathology.Nature communications · 2026Article
- Excitation-inhibition homeostasis in Alzheimer's disease: a selective multiscale review of mechanisms, sex differences, and therapeutic opportunities.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- The rise and deceleration of neuronal excitability in aging and Alzheimer's disease: Mechanisms, implications, and therapeutic targets.Ageing research reviews · 2026Review
- Exploring the pathogenic mechanisms of dementia risk factors: a task-fMRI study of mild cognitive impairment.Frontiers in neuroscience · 2026Article
- Elevated functional magnetic resonance imaging activity in cognitively normal participants predicts future dementia.Brain communications · 2026Article
- Longitudinal biomarker studies in human neuroimaging: capturing biological change of Alzheimer's pathology.Alzheimer's research & therapy · 2025Review
123 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundPrevious cross-sectional fMRI studies in subjects with prodromal Alzheimer disease (AD) have reported variable results, ranging from hypoactivation, similar to patients with AD, to paradoxically increased activation or hyperactivation compared to cognitively normal older individuals. We have hypothesized that subjects in early phases of prodromal AD may experience a period of hippocampal hyperactivation, followed by loss of hippocampal activation as the disease progresses.
methodsWe studied 51 older individuals without dementia (Clinical Dementia Rating [CDR] at baseline of 0, n = 21, and 0.5, n = 30) with longitudinal clinical and neuropsychological assessments, as well as fMRI during a face-name associative memory paradigm. Whole brain and region-of-interest analyses were applied to the longitudinal fMRI data.
resultsSubjects classified as CDR 0 at baseline showed no difference in fMRI activity over 2 years, whereas those who were CDR 0.5 at baseline demonstrated a decrease in fMRI activity in the right hippocampus (p < 0.001). Dividing the subjects on the basis of their clinical and neuropsychological change over the 2 years, we found that subjects with more rapid decline demonstrated both the highest hippocampal activation at baseline, and the greatest loss of hippocampal activation. These findings remained significant after accounting for age, hippocampal volume, and APOE epsilon4 carrier status.
conclusionsClinical decline is associated with loss of hippocampal activation in older subjects. Longitudinal fMRI provides a reliable indicator of brain activation over time, and may prove useful in identifying functional brain changes associated with cognitive decline on the trajectory toward clinical Alzheimer disease.
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.