ArticleBrain communications2021
The human hippocampus and its subfield volumes across age, sex and APOE e4 status.
Article in Brain communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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.
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.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Age-related differences in hippocampal subfield volumes across the human lifespan: A meta-analysis.Hippocampus · 2023Pooled it
- Accelerated hippocampal atrophy in APOE ε4 homozygotes and females: Longitudinal findings from the Tohoku Medical Megabank MRI study.Neuroradiology · 2026Article
- Lifetime Cannabis Use Is Associated With Brain Volume and Cognitive Function in Middle-Aged and Older Adults.Journal of studies on alcohol and drugs · 2026Article
- High-resolution MRI evidence for age- and sex-related changes in hippocampal subfield volume during healthy aging.GeroScience · 2026Article
- Diaschisis as Cerebello-Cortical Loop Dysfunction in Acute Ischemic Stroke: A Network Framework for Outcome Variability.Brain sciences · 2026Review
- The apolipoprotein gene: a modulating role on brain volume and cognitive function in carriers of the fragile X premutation.Neurobiology of disease · 2026Article
- Amyloid-Frontiers in aging neuroscience · 2026Article
- Sex-specific trajectories of hippocampal aging: structural changes and asymmetry across the lifespan.Neuroradiology · 2025Article
- Differential Roles of Neuro-Inflammatory Regulator, MAPK11 in Cortex and Hippocampus Following Post-Stroke Cognitive Impairments in Rats.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Gut microbiota and blood metabolites: unveiling their roles in hippocampal volume changes through Mendelian randomization and mediation analysis.Metabolic brain disease · 2025Article
- Impact ofProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Lower hippocampal volumes at baseline are associated with higher volume loss in healthy elderly.Frontiers in aging neuroscience · 2025Article
- Structural and functional sex differences in medial temporal lobe subregions at midlife.BMC neuroscience · 2024Article
- Blood biomarkers of neurodegeneration associate differently with amyloid deposition, medial temporal atrophy, and cerebrovascular changes in APOE ε4-enriched cognitively unimpaired elderly.Alzheimer's research & therapy · 2024Article
- Association Between Hippocampal Volumes and Cognition in Cerebral Amyloid Angiopathy.Neurology · 2024Article
- Alzheimer's disease genetic risk and changes in brain atrophy and white matter hyperintensities in cognitively unimpaired adults.Brain communications · 2024Article
- Prior infections are associated with smaller hippocampal volume in older women.Frontiers in dementia · 2024Article
- Consistent genes associated with structural changes in clinical Alzheimer's disease spectrum.Frontiers in neuroscience · 2024Article
- Proof-of-concept recall-by-genotype study of extremely low and high Alzheimer's polygenic risk reveals autobiographical deficits and cingulate cortex correlates.Alzheimer's research & therapy · 2023Article
- Astrocytes display ultrastructural alterations and heterogeneity in the hippocampus of aged APP-PS1 mice and human post-mortem brain samples.Journal of neuroinflammation · 2023Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Female sex, age and carriage of the apolipoprotein E e4 allele are the greatest risk factors for sporadic Alzheimer's disease. The hippocampus has a selective vulnerability to atrophy in ageing that may be accelerated in Alzheimer's disease, including in those with increased genetic risk of the disease, years before onset. Within the hippocampal complex, subfields represent cytoarchitectonic and connectivity based divisions. Variation in global hippocampal and subfield volume associated with sex, age and apolipoprotein E e4 status has the potential to provide a sensitive biomarker of future vulnerability to Alzheimer's disease. Here, we examined non-linear age, sex and apolipoprotein E effects, and their interactions, on hippocampal and subfield volumes across several decades spanning mid-life to old age in 36 653 healthy ageing individuals. FMRIB Software Library derived estimates of total hippocampal volume and Freesurfer derived estimates hippocampal subfield volume were estimated. A model-free, sliding-window approach was implemented that does not assume a linear relationship between age and subfield volume. The annualized percentage of subfield volume change was calculated to investigate associations with age, sex and apolipoprotein E e4 homozygosity. Hippocampal volume showed a marked reduction in apolipoprotein E e4/e4 female carriers after age 65. Volume was lower in homozygous e4 individuals in specific subfields including the presubiculum, subiculum head, cornu ammonis 1 body, cornu ammonis 3 head and cornu ammonis 4. Nearby brain structures in medial temporal and subcortical regions did not show the same age, sex and apolipoprotein E interactions, suggesting selective vulnerability of the hippocampus and its subfields. The findings demonstrate that in healthy ageing, two factors-female sex and apolipoprotein E e4 status-confer selective vulnerability of specific hippocampal subfields to volume loss.
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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.