O4‐03‐06: LONGITUDINAL ASSOCIATION BETWEEN APATHY AND COGNITIVE DECLINE IN PRE‐ AND POST‐SYMPTOMATIC GENETIC FRONTOTEMPORAL DEMENTIA
Bibliographic record
Abstract
Apathy is common in frontotemporal dementia (FTD), and is associated with worse prognosis. However, the effect of apathy on function and cognition, and its relevance before clinical diagnosis remain unclear. Here we examine longitudinal apathy-related and cognitive changes in pre-symptomatic gene carriers and patients in the Genetic FTD Initiative (GENFI) cohort. Five hundred and thirty-five participants were included: 211 pre-symptomatic mutation carriers, 122 clinically affected mutation carriers, and 202 family members without mutations (control group). A clinical and cognitive assessment was undertaken at baseline, year 1 and year 2. Apathy was measured by a clinical impression of severity clinical scale (0-3), and the Motivation subscale of the Revised Cambridge Behavioural Inventory (CBI-R, 0-20). A Latent Growth Curve model (LGCM) was implemented to assess longitudinal change in apathy measures, and in a composite cognitive score for executive functions. Univariate LGCM of all groups on apathy scores fitted the data well (χ2(5)=2.26, p=0.81, Root Mean Square Error of Approximation (RMSEA)=0.00, Comparative Fit Index (CFI)=1.00), with a significant longitudinal increase for pre-symptomatic carriers (est=0.63, se=0.29, z=2.20, p=0.03) and patients (est=1.63, se=0.48, z=3.40, p<0.001), but not controls. When included in the model, the time to expected year of onset (EYO) correlated with apathy changes in pre-symptomatic group (Std all=0.65 p=0.01). Bivariate LGCM across all subjects (χ2/df=2.17, RMSEA=0.05, CFI=0.97) indicated a significant association between increase in apathy scores and decline in executive function (Std all=−0.99, p=0.01). Executive performance in pre-symptomatic carriers declines significantly (est=−0.19, se=0.05, z=−4.09, p<0.001) and faster approaching the expected age at onset of symptoms (decline ∼ EYO: Std all=−0.46, p<0.001). We have demonstrated that apathy progresses in pre-symptomatic FTD, more so as one approaches the time of expected onset of symptoms. Furthermore, apathy interacts with the progression of executive impairment. The neural mediators of the relationship between apathy and cognitive decline are being investigated through MRI of this study cohort, but the current longitudinal analysis suggest that apathy may be a modifiable factor to protect function and cognition in those at risk of FTD.
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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 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 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 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| 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".