O1‐08‐01: THE NIH‐EXAMINER IS SENSITIVE TO COGNITIVE CHANGES IN ASYMPTOMATIC AND MILDLY SYMPTOMATIC FAMILIAL FRONTOTEMPORAL DEMENTIA
Bibliographic record
Abstract
At least 20% of cases of frontotemporal dementia (FTD) are caused by dominantly inherited mutations. As pharmaceutical agents are developed to treat familial FTD, mutation carriers in the presymptomatic and mildly symptomatic stages offer a unique opportunity for dementia prevention. There is a need for validated clinical endpoints that are sensitive to change in these early stages. The NIH-EXAMINER is a battery of executive function tests that is sensitive to early changes in sporadic FTD. We investigated whether the NIH-EXAMINER battery could detect longitudinal changes in cognition in mutation carriers before conversion to dementia. 52 mutation carriers (C9orf72, MAPT and GRN) with at least two acquisitions of EXAMINER data and a global Clinical Dementia Rating Scale (CDR) score < 1 (mean age=50.15; SD=12.82), were compared to 36 non-mutation carrier family members (mean age=49.37; SD=13.7). The NIH-EXAMINER yields an executive function (EF) composite, which includes measures of cognitive control, working memory and verbal fluency. We fitted linear mixed effects models (LME) with the EF composite score as the outcome variable and a random intercept for subject. We evaluated baseline differences and differential rates of decline between carriers and noncarriers by specifying a group*time interaction, covarying for age, education and gender. We fit a LME model to assess whether longitudinal changes in the EF composite were associated with changes in clinical symptomology (CDR Sum of Boxes, CDR-SB). We compared these results to Trail Making Test Part B (Trails B), a paper-and-pencil executive measure. Unstandardized regression coefficients (b) are reported below Carriers performed worse than noncarriers at baseline (b=-.32, p=.015), and there was a significant group*time interaction (b=-.14, p=.044), indicating that carriers had a more negative slope over time. Decreasing longitudinal EF performance was associated with increased clinical symptomology (CDR-SB,b=-.24, p<.001). The interaction coefficient was in the same direction but reduced by 30% when we restricted the analysis to carriers with CDR = 0 (b=-.09, p=.208). In contrast, carriers and noncarriers did not differ at baseline (b=31.33, p=.194) or in their rate of change on Trails B (b=13.51, p=.616). In familial FTD mutation carriers, the NIH-EXAMINER is sensitive to cognitive changes that precede conversion to dementia.
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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 | 0.009 | 0.016 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 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) | 0.003 | 0.001 |
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".