Cross-Sectional and Longitudinal Hippocampal Atrophy, Not Cortical Thinning, Occurs in Amyloid-Negative, p-Tau-Positive, Older Adults With Non-Amyloid Pathology and Mild Cognitive Impairment
Bibliographic record
Abstract
Introduction Alzheimer's disease (AD) is a degenerative disease characterized by pathological accumulation of amyloid and phosphorylated tau. Typically, the early stage of AD, also called mild cognitive impairment (MCI), shows amyloid pathology. A small but significant number of individuals with MCI do not exhibit amyloid pathology but have elevated phosphorylated tau levels (A-T+ MCI). We used CSF amyloid and phosphorylated tau to identify the individuals with A+T+ and A-T+ MCI as well as cognitively normal (A-T-) controls. To increase the sample size, we leveraged the Global Alzheimer's Association Interactive Network and identified 137 MCI+ and 61 A-T+ MCI participants. We compared baseline and longitudinal, hippocampal, and cortical atrophy between groups. Methods We applied ComBat harmonization to minimize site-related variability and used FreeSurfer for all measurements. Results Harmonization reduced unwanted variability in cortical thickness by 3.4% and in hippocampal volume measurement by 10.3%. Cross-sectionally, widespread cortical thinning with age was seen in the A+T+ and A-T+ MCI groups (p < 0.0005). A decrease in the hippocampal volume with age was faster in both groups (p < 0.05) than in the controls. Longitudinally also, hippocampal atrophy rates were significant (p < 0.05) when compared with the controls. No longitudinal cortical thinning was observed in A-T+ MCI group. Discussion A-T+ MCI participants showed similar baseline cortical thickness patterns with aging and longitudinal hippocampal atrophy rates as participants with A+T+ MCI, but did not show longitudinal cortical atrophy signature.
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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 | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| 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".