Relationships between cerebrovascular health and tau PET uptake are associated with global cognition
Bibliographic record
Abstract
Abstract Background Brain accumulation of tau and cerebrovascular dysfunction are both important contributors to AD pathogenesis, but associations between vascular health and tau levels, and their effects on clinical outcome, are poorly understood. We investigated these associations in a cross‐sectional study, by performing comparisons between cerebral blood flow (CBF), measured with ASL perfusion MRI, and tau PET uptake, measured with [18F]flortaucipir (FTP). In a subgroup, we assessed relationships between tau uptake and a CSF marker of vascular health known to be associated with impaired cognition, soluble platelet‐derived growth factor beta (sPDGFR‐β). Method We conducted discovery and replication analyses using data from USC (n=68) and ADNI (n=136), respectively. Voxelwise analyses assessed relationships between CBF and FTP standardized uptake value ratio (SUVR), the results of which were used to mask the replication analysis. Secondary analyses were performed on the replication dataset with a gray matter mask. Analyses were corrected for age, sex, gray matter volume, and diagnosis (when appropriate), with voxelwise and cluster‐level thresholds of p<0.001 and p<0.05, respectively. General linear models were used to determine if CBF‐FTP relationships differed between diagnostic groups, as well as between high and low performance on the Montreal Cognitive Assessment (MoCA), a measure of global cognition. Mediation models assessed the relationship between tau, sPDGFR‐β, and cognition. Result In the discovery cohort, we observed negative CBF‐FTP correlations mainly in lateral and inferior temporal regions, that were largely replicated in the ADNI cohort. Secondary analyses demonstrated that early negative CBF‐FTP correlations increased in spatial extent and strength of correlation with increased disease severity. Stronger negative CBF‐FTP correlations were observed in participants with more advanced diagnoses and in those with poorer global cognitive performance. sPDGFR‐β was a significant mediator of the relationship between inferior temporal tau uptake and MoCA. Conclusion Our results provide evidence that associations between the cerebrovascular system and tau binding may affect cognition across the AD spectrum. Importantly, the sPDGFR‐β analysis suggests that vascular dysfunction may contribute to cognitive impairment via elevations in tau, potentially caused by reduced tau clearance. Future, longitudinal studies are needed to explore the complex temporal relationship between tau deposition and vascular health.
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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 | 0.008 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| 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".