APOE ε4-associated hippocampal atrophy trajectories across the Alzheimer's disease continuum: a systematic review, meta-analysis, and longitudinal validation.
The 4 matches
- [1] § Methods › Meta-analysis strategy ↔ meta/meta.R, lines 120–261 · score 0.65 · bias corrected, meta regression, trim, Baujat, multiverse, fill
- [2] § Methods › Statistical models ↔ ADNI/adni_analysis.py, lines 67–95 · score 0.62 · field strength, APOE4 dosage, ADNI model, baseline diagnosis, ICV, Sex
- [3] § Results › Establishing the baseline effect and sources of heterogeneity ↔ meta/meta.R, lines 120–261 · score 0.59 · bias corrected, meta regressions, trim, female, fill, uncorrected
- [4] § Methods › Statistical models ↔ ADNI/adni_analysis.py, lines 133–170 · score 0.52 · field strength, baseline diagnosis interaction, CN, ICV, sex, age
Paper
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The authors' code
R · 505 lines · 30 KB · no license · 2 matches
meta.R at commit 09b915a, no license · at the source
Overview
- Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, Xinjiang, China
- Shenzhen X-Institute, Shenzhen, China
- College of Mathematics and System Science, Xinjiang University, Urumqi, Xinjiang, China
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 (N = 4, 311) and indicated reduced hippocampal volume in carriers (ICV-corrected stratum: SMD = −0.41, 95% CI [−0.67, −0.16], p = 0.004; I2 = 74.0%), with the effect absent in uncorrected analyses. Longitudinal gene-dose models, run independently in the post-QC NACC LMM sample (N = 3, 239; imaging extraction N = 3, 248) and ADNI (N = 1, 150) cohorts and combined via fixed-effect meta-analysis, demonstrated a dose-dependent acceleration of hippocampal atrophy: homozygotes exhibited a pooled additional volume loss of −58.25 mm3/
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 (I2 = 63.0%).
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://
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wyqmath/admeta
09b915a36aec7144152e2946681423fc39d8d70e, 22 May 2026Availability: 1 check, the latest on 27 September 2026: the link answers
- 27 September 2026: the link answers
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meta.R — R, 505 lines, 2 matches, shown from its source - README.md — Text, 64 lines, shown from its source
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Data availability statement
The code used for the meta-analysis and longitudinal modeling is publicly available in the GitHub repository: https://
Reproduced under the paper's license (CC BY), from the paper cited above.
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Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, pages, dates, 7 authors, 5 keywords, 1 funder, 72 references.
Cite
This paper
Cai, M., Lei, H., Zhang, Y., Zou, J., Cao, W., Wang, Y., & Wei, K. (2026). APOE ε4-associated hippocampal atrophy trajectories across the Alzheimer's disease continuum: a systematic review, meta-analysis, and longitudinal validation. Frontiers in aging neuroscience, 18, 1847611. https://
BibTeX
@article{cai2026apoe,
author = {Cai, Minnuo and Lei, Hang and Zhang, Yuetong and Zou, Jiaxiang and Cao, Wanjing and Wang, Yiquan and Wei, Kai},
title = {{APOE ε4-associated hippocampal atrophy trajectories across the Alzheimer's disease continuum: a systematic review, meta-analysis, and longitudinal validation}},
journal = {Frontiers in aging neuroscience},
year = {2026},
month = jul,
volume = {18},
pages = {1847611},
publisher = {Frontiers Media SA},
issn = {1663-4365},
doi = {10.3389/
url = {https://
pmid = {42459526},
pmcid = {PMC13369312}
}
RIS
TY - JOUR
AU - Cai, Minnuo
AU - Lei, Hang
AU - Zhang, Yuetong
AU - Zou, Jiaxiang
AU - Cao, Wanjing
AU - Wang, Yiquan
AU - Wei, Kai
TI - APOE ε4-associated hippocampal atrophy trajectories across the Alzheimer's disease continuum: a systematic review, meta-analysis, and longitudinal validation
T2 - Frontiers in aging neuroscience
J2 - Front Aging Neurosci
PY - 2026
DA - 2026/
VL - 18
SP - 1847611
SN - 1663-4365
PB - Frontiers Media SA
DO - 10.3389/
UR - https://
LA - en
ER -
CSL-JSON
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