Biomarker‐Driven Patterns of Hippocampal Subfield Atrophy in Amnestic Mild Cognitive Impairment
Bibliographic record
Abstract
BACKGROUND: Hippocampal atrophy is a well-established hallmark of Alzheimer's disease (AD), closely associated with cognitive decline and disease progression, even in the earliest symptomatic stages. Despite growing evidence that subfield-specific atrophy patterns could serve as sensitive biomarkers for early diagnosis and tracking disease progression, there remains a significant gap in understanding how these subfields are differentially impacted across different stages of AD. In this study, we explore longitudinal rates of atrophy in hippocampal subfields in individuals with amnestic mild cognitive impairment (MCI). METHOD: Hippocampal subfields volumes were extracted from volumetric, T1-weighted MRI images from the Alzheimer's Disease Neuroimaging Initiative using Freesurfer (v 7.4.1). We included individuals with MCI who underwent cerebrospinal fluid (CSF) collection and MRI studies at baseline and after 1 year. Participants were categorized according to baseline CSF levels of amyloid and phosphorylated-tau proteins as: A-T-, A+T-, A-T+, and A+T+. Using generalized linear models, we evaluated the effect of biomarker subgroups on hippocampal subfield atrophy rates, controlling for age, sex, and whole hippocampal volume. RESULT: Table 1 summarizes demographic data for each biomarker group. Using the A-T- group as reference, higher rates of atrophy were observed in the A-T+ group in the subiculum, bilaterally. The A+T- group showed differences in the left presubiculum and in the subiculum, bilaterally. In the A+T+ group, faster atrophy was observed in the bilateral parasubiculum, bilateral subiculum, bilateral presubiculum, bilateral CA1, right CA4, and right dentate gyrus (granule cell and molecular layers) - Figure 1. CONCLUSION: This study reveals distinct patterns of hippocampal subfield atrophy in amnestic MCI, according to amyloid-beta (A) and phosphorylated tau (T) biomarker profiles. The A-T+ group exhibited a unique pattern of subfield vulnerability, primarily affecting the subiculum, suggesting that tau pathology alone may target specific regions of the hippocampus. In contrast, the A+T+ group showed widespread atrophy across multiple subfields, indicating that combined amyloid and tau pathology leads to more extensive hippocampal degeneration. These findings highlight the potential of subfield-specific atrophy patterns as sensitive biomarkers for differentiating early AD stages and tracking disease progression. Future studies should investigate how these patterns correlate with cognitive decline and their predictive value for dementia conversion.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".