Neurodevelopmental effects of genetic frontotemporal dementia mutations revealed by total intracranial volume differences
Bibliographic record
Abstract
ABSTRACT Background and Objectives Converging evidence hints at neurodevelopmental effects in people at risk of genetic frontotemporal dementia (FTD), including associations between FTD-causing mutations and neurodevelopmental disorders, and differences in young adult mutation carriers compared to familial non-mutation carriers in total intracranial volume (TIV) and cognition. We aimed to investigate TIV and educational attainment differences between adult mutation carriers and familial non-mutation carriers, as measures of the structural and functional neurodevelopmental effects of the FTD-causing genetic mutations. Methods This cross-sectional cohort study was facilitated through the FTD Prevention Initiative (FPI). Participants, aged 18 to 86 years, were pathogenic mutation carriers of GRN , MAPT , or C9orf72 , or familial non-carriers. ANCOVAs were computed per gene to compare outcome means for the main effect of group by carrier status, while controlling for birth decade, sex, and visit site (to account for unique scanners and educational systems). Pearson’s correlations were used to examine associations between TIV and education. Results Nine-hundred two mutation carriers (mean±SD; age=50.0±13.2 years, sex=55% female, n ( GRN )=298, n( MAPT )=187, n ( C9orf72 )=417) were compared to 532 familial non-carriers (age=48.0±12.9 years, sex=58% female, n ( GRN )=201, n( MAPT )=114), n ( C9orf72 )=217). Consistent with prior findings in young adults, GRN carriers showed larger TIV compared to familial non-carriers (95% confidence interval [CI]=1431994-1457123, p =0.049, η 2 p =0.008). Larger TIV correlated with higher years of education in GRN carriers (95% CI=0.01-0.24, r (295)=0.12, p =0.03) and GRN non-carriers (95% CI=0.08-0.34, r(198)=0.21, p =0.002). MAPT carriers demonstrated smaller TIV than non-carriers (95% CI=1417819-1450628, p =0.039, η 2 p =0.02). Models with C9orf72 and education as outcome variables did not reveal significant differences. Discussion In support of the neurodevelopmental hypothesis of FTD, GRN and MAPT mutations are linked to likely structural neurodevelopmental changes in TIV, some of which correlate to years of education. These findings motivate further research to identify mechanisms by which FTD mutations influence neurodevelopment and ascertain their suitability as targets for interventions.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Direct model labels (unvalidated)
Per-model category and study-design labels from the labeling rounds. They are machine output, unvalidated, and the disagreement between models ships as data. No study design here is MEDLINE-validated yet.
| Model arm | Categories | Study design | Confidence |
|---|---|---|---|
| gemma | no category Domain: not available · Genre: Empirical About the Canadian research system: no · About a Canadian topic: no | Observational | high |
| gpt | no category Domain: not available · Genre: Empirical About the Canadian research system: no · About a Canadian topic: no | Observational | high |
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| 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 | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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, unvalidatedLabeled directly by 2 models reading the full record.
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".