Early anterior cingulate involvement is seen in presymptomatic MAPT P301L mutation carriers
Bibliographic record
Abstract
Abstract Background PET imaging of glucose metabolism has revealed presymptomatic abnormalities in genetic FTD but has not been explored in MAPT P301L mutation carriers. This study aimed to explore the patterns of presymptomatic hypometabolism and atrophy in MAPT P301L mutation carriers. Methods Eighteen asymptomatic members from five families with a P301L MAPT mutation were recruited to the study, six mutation carriers, and twelve mutation-negative controls. All participants underwent standard behavioural and cognitive assessment as well as [18F]FDG-PET and 3D T1-weighted MRI brain scans. Regional standardised uptake value ratios (SUVR) for the PET scan and volumes calculated from an automated segmentation for the MRI were obtained and compared between the mutation carrier and control groups. Results The mean (standard deviation) estimated years from symptom onset was 12.5 (3.6) in the mutation carrier group with a range of 7 to 18 years. No differences in cognition were seen between the groups, and all mutation carriers had a global CDR plus NACC FTLD of 0. Significant reduction in [18F] FDG uptake in the anterior cingulate was seen in mutation carriers (mean 1.25 [standard deviation 0.07]) compared to controls (1.36 [0.09]). A similar significant reduction was also seen in grey matter volume in the anterior cingulate in mutation carriers (0.60% [0.06%]) compared to controls (0.68% [0.08%]). No other group differences were seen in other regions. Conclusions Anterior cingulate hypometabolism and atrophy are both apparent presymptomatically in a cohort of P301L MAPT mutation carriers. Such a specific marker may prove to be helpful in stratification of presymptomatic mutation carriers in future trials.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 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".