MRI correlates of neuropsychiatric symptom progression in pre‐dementia <i>GRN</i> and <i>C9orf72</i> mutation carriers
Bibliographic record
Abstract
Abstract Background Frontotemporal dementia (FTD) patients with mutations in the C9orf72 or the GRN genes frequently exhibit neuropsychiatric symptoms (NPS), which may precede the onset of dementia. We hypothesized that the burden and progression of NPS in pre‐dementia mutation carriers are associated with structural abnormalities detectable in brain MRI. Method We analyzed data from 42 participants before onset of dementia (11 C9orf72+ mutation carriers, 8 GRN+ mutation carriers, and 23 non‐carrier family members (NCs); mean±SD age: 46y±11, 50y±9, and 53y±8 respectively) recruited through the University of British Columbia FTD Study. Participants were assessed longitudinally for NPS with Neuropsychiatric Inventory (NPI), Frontal Behavioural Inventory (FBI) and Iowa Scale of Personality Change (ISPC) (mean follow‐up: 8.4y). Participants also underwent 1.5T MRI at the first and third annual visits (mean interval: 28±8m). If a participant developed FTD during the follow‐up (N=2), we only analyzed observations collected before the conversion. We processed T1‐weighted MRI to calculate annualized volumetric changes in the grey‐matter, the white‐matter and the hypointense white‐matter signal‐abnormalities (WMSA), within the entire brain and lobar region‐of‐interests. We applied a random‐slope model to the NPI, FBI and ISPC scores to estimate subject‐specific slopes of their progression. Then, we applied a linear model to evaluate the association between the estimated slopes and the MRI measures, among the genetic groups. Covariates included sex, age, baseline assessment scores, baseline WMSA and total white‐matter volumes. Result There were non‐significant baseline group differences in the MRI or NPS measures. Overall, a higher rate of frontal lobar WMSA accumulation was associated with a higher rate of NPI score increase. However, GRN+ carriers had a faster progression of NPS compared to NCs, and the higher NPI slope was associated with a higher rate of frontal lobar white‐matter volume loss. The FBI and ISPC slopes were not significantly associated with the MRI measures. Conclusion Prior to the onset of FTD, the emergence of NPS in mutation carriers may be correlated with the degree of frontal lobar white‐matter lesions. In GRN+ carriers, the progression of NPS, as represented by NPI score increases, may also be associated with frontal white‐matter volume loss.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".