Executive function deficits in genetic frontotemporal dementia: results from the GENFI study
Bibliographic record
Abstract
Abstract Background Executive dysfunction is a core feature of frontotemporal dementia (FTD). Whilst there has been extensive research into such impairments in sporadic FTD, there has been little research in the familial forms. Methods 752 individuals were recruited in total: 214 C9orf72 , 205 GRN and 86 MAPT mutation carriers, stratified into asymptomatic, prodromal and fully symptomatic, and 247 mutation negative controls. Attention and executive function were measured using the Weschler Memory Scale-Revised (WMS-R) Digit Span Backwards (DSB), the Wechsler Adult Intelligence Scale-Revised Digit Symbol task, the Trail Making Test Parts A and B, the Delis-Kaplan Executive Function System Color Word Interference Test and verbal fluency tasks (letter and category). Linear regression models with bootstrapping were used to assess differences between groups. Correlation of task score with disease severity was also performed, as well an analysis of the neuroanatomical correlates of each task. Results Fully symptomatic C9orf72, GRN and MAPT mutation carriers were significantly impaired on all tasks compared with controls (all p<0.001), except on the WMS-R DSB in the MAPT mutation carriers (p=0.147). Whilst asymptomatic and prodromal C9orf72 individuals also demonstrated deficits compared with controls, neither the GRN or MAPT asymptomatic or prodromal mutation carriers showed significant differences. All tasks significantly correlated with disease severity in each of the genetic groups (all p<0.001). Conclusions Individuals with C9orf72 mutations show difficulties with executive function from very early on in the disease and this continues to deteriorate with disease severity. In contrast, similar difficulties occur only in the later stages of the disease in GRN and MAPT mutation carriers. This differential performance across the genetic groups will be important in neuropsychological task selection in upcoming clinical 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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 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".