ArticleFrontiers in aging neuroscience2026
APOE ε4 as a predictor of cognitive decline and its interaction with hippocampal volume in Alzheimer's disease.
Article 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 2 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
2 citing papers in PubMed, 1 synthesis or guideline pooled it.
- APOE ε4-associated hippocampal atrophy trajectories across the Alzheimer's disease continuum: a systematic review, meta-analysis, and longitudinal validation.Frontiers in aging neuroscience · 2026Pooled it
- APOE ε4 Allele Dose and Time to Clinical Conversion from Mild Cognitive Impairment to Alzheimer's Disease Dementia: An ADNI Survival Analysis.Biomedicines · 2026Article
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background/Introduction: The apolipoprotein E (APOE) ε4 allele is the strongest known genetic risk factor for late-onset Alzheimer's disease, and hippocampal atrophy is among the most reliable structural biomarkers of neurodegeneration. While both are independently associated with cognitive decline, whether APOE ε4 dose modulates the hippocampal volume-cognition relationship longitudinally in sporadic Alzheimer's disease remains underexplored at adequate statistical power. Methods: This study analyzed data from 2,417 Alzheimer's Disease Neuroimaging Initiative participants with complete APOE genotypes, intracranial volume-adjusted hippocampal volumes, and longitudinal cognitive assessments spanning a mean follow-up of 4.2 years and up to 19.3 years with an average of 4.9 visits per participant. Linear mixed-effects models with random intercepts and slopes per subject estimated cognitive trajectories across the Mini-Mental State Examination (MMSE), Clinical Dementia Rating Sum of Boxes (CDR-SB), and Alzheimer's Disease Assessment Scale Cognitive Subscale 13 (ADAS-Cog13) as a function of time, APOE ε4 dose, and ICV-adjusted hippocampal volume, including their three-way interaction and adjusting for age, sex, education, baseline diagnosis, and depression. Cox proportional hazards models were used to assess conversion risk. Results: A clear APOE ε4 dose-response gradient was observed at baseline across all cognitive and hippocampal measures (all p < 0.001). Linear mixed-effects models revealed a significant three-way interaction of time × APOE ε4 dose × hippocampal volume on MMSE ( Discussion/Conclusion: These findings demonstrate that APOE ε4 genotype significantly modulates the longitudinal relationship between hippocampal volume and cognitive decline, supporting the integration of APOE genotype and structural hippocampal imaging for refined individual risk stratification in Alzheimer's disease.
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