SynthesisFrontiers in aging neuroscience2026
APOE ε4-associated hippocampal atrophy trajectories across the Alzheimer's disease continuum: a systematic review, meta-analysis, and longitudinal validation.
Synthesis in Frontiers in aging neuroscience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Geometric Fragility in Alzheimer's Disease: Probing the Loss of Hippocampal Hierarchical Abstraction via Contrastive Point Cloud Modeling.bioRxiv : the preprint server for biology · 2026Article
Corrections and comments
- Update ofAPOE2025
Authors and funding
7 authors.
Funding
Abstract
Background: Predicting patient-specific neurodegenerative trajectories is essential for targeted interventions in Alzheimer's disease. Although the APOE-ε4 allele is the predominant genetic risk factor for hippocampal atrophy, whether its structural impact reflects a static developmental phenotype or an accelerated neurodegenerative process conditional on amyloid pathology remains unresolved. Objectives: To quantify the effect of APOE-ε4 on hippocampal volume via cross-sectional meta-analysis, and to validate the gene-dose effect through independent longitudinal modeling in two cohorts. Eligibility criteria: Original observational neuroimaging studies reporting hippocampal volume stratified by APOE genotype in human participants across the Alzheimer's disease continuum. Information sources: PubMed, Embase, Web of Science, and Cochrane Library were searched from inception to August 2025. Risk of bias: Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS) adapted for cross-sectional studies. Included studies and synthesis of results: The meta-analysis included 18 studies ( Limitations: Biomarker-stratified analyses used baseline-only CSF measurements subject to time-varying confounding and should be interpreted as exploratory. Moderate between-cohort heterogeneity was observed for the heterozygote effect ( Conclusions and implications: These findings provide two-cohort evidence for a dose-dependent APOE-ε4 effect on hippocampal atrophy rates. Exploratory biomarker-stratified analyses in ADNI suggest this acceleration may be conditional on amyloid-β positivity, a hypothesis requiring validation with time-varying causal models. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251243460, PROSPERO: CRD420251243460.
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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.