Tau accumulation using [<sup>18</sup>F]MK6240 PET is associated with increase in executive dysfunction in prodromal AD
Bibliographic record
Abstract
Abstract Background Decline in executive function has been noted to precede other forms of cognitive decline in the prodromal stage of Alzheimer’s disease (Clark et al., 2011). The D‐KEFS Color‐Word Interference test (CWIT) is a cognitive test that measures executive function across several conditions. Few studies have explored the relationship between tau deposition and executive dysfunction. However, to date, no study has explored this relationship in prodromal AD. This study aimed at exploring such associations. Method We looked at cognitively unimpaired and impaired elderly individuals from the TRIAD cohort in Montreal, QC who underwent neuropsychological evaluations across 2 time points. In vivo tau accumulation was assessed at baseline with [18F]‐MK6240 PET. Standardized uptake value ratio was calculated 90‐110 minutes post‐injection using cerebellar grey matter as the reference region. Voxel‐wise linear regression models were applied with the rate of change of CWIT condition 3 and 4 completion times as predictor variables with tau tracer binding being the response variable. Age, sex, education, Geriatric Depression Scale score, APOEε4, diagnostic group, and amyloid‐β status were included as covariates in regression models. Results were corrected for multiple comparisons using random field theory with a cluster threshold of p < .001. Result A total of 105 (CN=65;MCI=36;AD=4) individuals were included in this analysis, with mean follow‐up time of neuropsychological evaluation being 15.9 months. We found that brain [18F]‐MK6240 uptake was correlated with change in D‐KEFS CWIT condition 3 and 4 completion times, with a greater pattern of association in condition 3 (inhibition). For condition 3, associations were strongest in the precuneus, posterior cingulate, and primarily right dorsal frontal and parietal regions. For condition 4 (flexibility), we found a strong association in the left temporal pole and left dorsal frontal regions. Conclusion These results support previous claims that tau follows a distinct regional distribution similar to that of the dorsal attention network which is related to higher order cognitive function such an inhibition and switching (Hansson et al., 2017). Additionally, given that most individuals in this study were CN or MCI, our findings suggest that tau pathology is associated with a decrease in executive function even in prodromal stages 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 | 0.000 | 0.001 |
| 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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".