[O2–01–06]: FRONTO‐SUBCORTICAL HYPOPERFUSION IN PRESYMPTOMATIC FTD IS ASSOCIATED WITH BEHAVIORAL MEASURES, BUT NOT COGNITIVE DEFICITS: THE GENFI STUDY
Bibliographic record
Abstract
Frontotemporal dementia (FTD) is a highly heritable neurodegenerative condition. Genetic mutations in the three genes account for the majority of genetic FTD: Chromosome 9 open reading frame 72 (C9orf72), progranulin (GRN), and microtubule-associated protein tau (MAPT). We hypothesize that in pre-symptomatic mutation carriers, regional hypoperfusion in frontal regions will associate with behavioral and cognitive measures. In the large multi-centre pre-symptomatic genetic FTD study(GENFI), we previously identified “regions of interest (ROIs) of cerebral hypoperfusion” using a voxel-based analysis (VBA) of Arterial Spin Labeling MRI data from presymptomatic mutation carriers (n=95; C9orf72=30, GRN=48, MAPT=17) vs. non-carrier controls (n=100). These hypoperfusion ROIs were then associated with cognitive and behavioural measures using multiple linear regression. Specifically, in these models, the dependent variables included: global cognition (Mini-Mental State Examination), executive function (Trail making test A and B), language (Boston naming and verbal fluency), logical memory (immediate and delayed recall), working memory (forward and backward digit span), and behavioural measures (Cambridge Behavior Inventory-Revised [CBI-R] and FTD rating scale). Analyses were repeated after stratifying on mutation, and all models were adjusted for age, sex, and education. The hypoperfusion ROIs in carriers identified from the VBA included: paracingulate, orbitofrontal/insula, frontal pole (right), putamen, frontal pole (bilateral), and middle frontal gyrus/inferior frontal gyrus/superior frontal gyrus (MFG, IFG, SFG). No associations were observed between ROIs and cognitive domains in carriers or non-carriers. In the ROI-behavior analyses using CBI-R score, significant interactions were observed between cerebral perfusion and carrier-status across the ROIs. In carriers only, hypoperfusion in the paracingulate region [β 0.16 (95% CI:0.23,0.04) p <0.001, p-interaction <0.001], frontal pole (right) [β 0.14 (95% CI:0.06,0.22) p<0.001, p-interaction 0.01], putamen [β 0.20 (95% CI:0.06,0.34) p= 0.006, p-interaction =0.01], frontal pole (bilateral) [β 0.14 (95% CI:0.06,0.22) p <0.001, p-interaction 0.008], and MFG/IFG/SFG [β 0.13 (95% CI: 0.06,0.21) p <0.001, p-interaction 0.01] was strongly associated with behaviour features. No ROI-behavior associations were observed in non-carriers. In subsequent mutation stratified analyses, we found that observed associations were driven by MAPT carriers. Cerebral hypoperfusion within frontal-subcortical regions in presymptomatic FTD is associated with early behavioral changes but not with cognitive deficits.
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
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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.007 | 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".