Tau-related reduction of glucose metabolism in mild cognitive impairment occurs independently of APOE ε4 genotype and is gradually modulated by β-amyloid
Bibliographic record
Abstract
Abstract Background PET imaging studies have shown that spatially distributed measurements of β-amyloid are significantly correlated with glucose metabolism in Mild Cognitive Impairment (MCI) independently of the APOE ε4 genotype. In contrast, the relationship between tau and glucose metabolism at different stages of Alzheimer’s Disease (AD) has not been fully understood. Objective We hypothesize that spatially distributed scores of tau PET are associated with an even stronger reduction of glucose metabolism, independent of the APOE ε4 genotype and gradually modulated by β-amyloid. Methods We applied a cross-sectional statistical analysis to concurrent [18F]flortaucipir PET, [18F]florbetapir PET, and 2-[18F]fluoro-2-deoxyglucose (FDG) PET images from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. We employed a Singular Value Decomposition (SVD) approach to the cross-correlation matrix between tau and the FDG images, as well as between tau and β-amyloid PET images. The resulting SVD-based tau scores are associated with cortical regions where a reduced glucose metabolism is maximally correlated with distributed patterns of tau, accounting for the effect of spatially distributed β-amyloid. Results From a population of MCI subjects, we found that the SVD-based tau scores had their maximal spatial representation within the entorhinal cortex and the lateral inferior temporal gyrus, and were significantly correlated with glucose metabolism in several cortical regions, independently from the confounding effect of the β-amyloid scores and APOE ε4. Moreover, β-amyloid gradually modulated the association between tau and glucose metabolism. Conclusions Our approach uncovered spatially distributed patterns of the tau-glucose metabolism relationship after accounting for the β-amyloid effects. We showed that the SVD-based tau scores have a strong relationship with decreasing glucose metabolism. By highlighting the more significant role of tau, rather than β-amyloid, on the reduction of glucose metabolism, our results could have important consequences in the therapeutic treatment of AD.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| 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".