O5‐01‐06: Baseline CSF p‐tau and fibrillary amyloid load predict mesial temporal hypometabolism in 24 months' follow‐up in cognitively normal subjects
Bibliographic record
Abstract
Identification of cognitively normal (CN) individuals destined to develop hypometabolism has immediate applications on preventive clinical trials. Current biomarker progression models of Alzheimer's disease propose abnormal tau hyperphosphorylation preceding hypometabolism. From the Alzheimer's Disease Neuroimaging Initiative (ADNI), we investigated whether combined measures of amyloid and tau pathology predict subsequent hypometabolism in cognitively normal subjects. CN individuals (n=108) who had CSF total tau (t-tau), phospho-tau181p (p-tau), Aβ1–42, [18F]FDG and [18F]Florbetapir measurements in baseline and 24 month follow-up were analyzed. Subjects were dichotomized using CSF Aβ1–42, t-tau and p-tau published cutoffs, and further divided in [18F]Florbetapir positive and negative. [18F]FDG and [18F]Florbetapir PET SUVRs were computed using the pons and cerebellum as reference regions, respectively. We tested our hypothesis using voxel-based linear model, which included 24 month [18F]FDG PET SUVR changes as a response variable and global [18F]Florbetapir PET SUVR, CSF Aβ1–42, t-tau, p-tau status as factors; model was corrected for age, gender and APOE4 status. Were FDR corrected (p < 0.001). Table 1 summarizes the study demographics. Figure 1 shows areas in which metabolic declines in [F]FDG were predicted by the interaction of baseline p-tau and [F]Florbetapir PET status. [F]FDG SUVRs did not differ between the groups composed by the dichotomization of CSF p-tau and Global [F]Florbetapir PET. In contrast, the group with abnormal CSF p-tau and [F]Florbetapir PET status had 20-30% lower follow-up [F]FDG SUVRs mean in the mesial temporal structures. Voxel-based factorial using CSF Aβ1–42 or t-tau values showed no significant results. The present results support the conceptual framework in which pathological levels of brain amyloidosis and hyperphosphorylated tau precedes metabolic declines in preclinical stages of AD. In fact, the regions displaying the highest rate of hypometabolism are confined to brain circuits vulnerable to early stages of tau pathology as described by Braak. The present data also support previous research indicating the coexistence of amyloid and p-tau pathology as determinants of disease progression.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".