P4‐054: Cerebral cortical atrophy, brain infarcts, and clinical expression of Alzheimer pathology: Findings from The Nun Study
Bibliographic record
Abstract
The observation that not all who meet neuropathologic criteria for Alzheimer's disease (AD) are demented has stimulated interest in the concept of cognitive reserve. Loss of cerebral cortical tissue is hypothesized to contribute to the loss of cognitive reserve. Vascular factors may also be important in cognitive reserve. Among those who meet neuropathologic criteria for AD, atrophy and brain infarcts may distinguish between those who resist clinical expression of AD (asymptomatic AD) and those who become demented (symptomatic AD). The Nun Study is a longitudinal study of aging in 678 participants 75+ years; 237 met CERAD neuropathologic criteria for AD. Cerebral cortical atrophy, brain infarcts, and neuropathologic diagnosis of AD were determined by gross and microscopic postmortem examinations. Cerebral cortical atrophy was strongly associated with symptomatic AD. This association persisted after adjustment for age at death, education, and APOE-e4 in logistic regression models of the presence of any atrophy (odds ratio [OR]=6.58, 95% CI=2.92–15.95), and showed an increasing impact of atrophy from mild (OR=4.82; 95% CI=2.08–12.08) to moderate levels (OR=9.75; CI=2.00–37.19). Severe levels of atrophy showed a strong, significant association (OR=111.83; 95% CI=15.07–1000+), but confidence limits could not be accurately calculated due to the paucity of subjects with severe atrophy and asymptomatic AD (1/22 or 4.5%). Frontal (OR=3.08; 95% CI=1.71–5.62), temporal (OR=5.29; 95% CI=2.71–10.98) and parietal atrophy (OR=6.33; 95% CI=2.10–27.46) were all significantly associated with symptomatic AD; occipital atrophy was not a significant predictor, but few individuals (n=6) showed atrophy in this region. Large or lacunar brain infarcts were also significantly associated with symptomatic AD (OR=2.56; 95% CI=1.33–5.08) and remained significant in the presence of atrophy except for higher (moderate or severe) levels of atrophy. The presence of atrophy and brain infarcts significantly reduced the ability to resist clinical expression of AD pathology. Although the impacts of these pathologies are largely independent, brain infarcts may have a reduced contribution to symptomatic AD at more severe levels of atrophy. Studies of the association and interactions of brain pathologies on clinical expression of AD pathology may provide insight into mechanisms and predictors of cognitive reserve.
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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 | 0.003 | 0.006 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".