Progression of neuropsychiatric symptoms in pre‐dementia <i>GRN</i> and <i>C9orf72</i> mutation carriers
Bibliographic record
Abstract
Abstract Background Neuropsychiatric symptoms (NPS) are common in frontotemporal dementia (FTD) patients and may precede the clinical diagnosis of dementia. We hypothesized that GRN and C9orf72 mutation carriers have increased baseline burden and rates of progression of NPS compared to non‐carriers prior to the onset of dementia. To investigate, we examined a longitudinal cohort of FTD mutation carriers and non‐carrier family members. Method We analyzed data from 80 participants (21 C9orf72+ mutation carriers, 10 GRN+ mutation carriers, and 49 non‐carrier family members (NCs); mean±SD age in years: 47±13, 51±9, and 54±13 respectively) recruited through the University of British Columbia FTD Study. NPS were assessed annually with Neuropsychiatric Inventory (NPI), Frontal Behavioural Inventory (FBI) and Iowa Scale of Personality Change (ISPC) with a mean follow‐up of 5.8 years. For ISPC, we used both the “Change” (“Now” minus “Before”) and the “Now” measures. If a participant developed FTD during the follow‐up (N=2), we only analyzed observations collected before the conversion. We initially compared the baseline burden of NPI, FBI and ISPC adjusted for age and sex, among C9orf72+ carriers, GRN+ carriers and NCs. We then used random‐intercept mixed models to compare the rates of progression of NPS among genetic groups using total NPI, FBI, ISPC change and ISPC now scores as outcome measures and genetic status, sex, respective baseline scores, expected years to onset (EYO) and genetic group*EYO interaction term as dependent variables. Result There were no significant group differences in baseline demographic features or neuropsychiatric measures. In longitudinal assessments, NCs demonstrated minimal change in NPS measures. GRN+ carriers had significantly higher progression rates of NPI (p<0.0001) and ISPC “Now” (p=0.0004) compared to NCs. However, there were no significant differences in the NPS progression rates between C9orf72+ carriers and NCs. Conclusion Although there was no baseline difference in the burden of NPS among the genetic groups, GRN+ carriers had a faster progression of NPS compared to NCs prior to the onset of dementia. Future work is warranted to investigate the potential association between the NPS trajectories and structural/functional brain changes in FTD mutation carriers.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 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".