IC‐P‐039: Changes in cerebral blood flow in presymptomatic mutation Carriers of Familial Frontotemporal Dementia (FTD‐3), Measured with MRI
Bibliographic record
Abstract
Frontotemporal dementia linked to chromosome 3 (FTD-3) is an autosomal dominantly inherited neurodegenerative disease caused by a truncating mutation in CHMP2B (1). The disease is characterized by insidious and progressive changes in personality, behaviour and cognition (2). The protein CHMP2B is a part of the ESCRTIII complex necessary for endosomal trafficking and protein degradation (1,3). Studies in presymptomatic CHMP2B-mutation carriers have shown both localized cortical (4) and more generalized brain atrophy (5). The purpose of this study is to assess functional change in the presymptomatic stage of the disease as indicated by local changes in cerebral blood flow (CBF). Presymptomatic mutation carriers and first-degree related non-carriers were MRI-scanned with a spin-echo sequence sensitive mainly to CBF in capillaries. CBF images were co-registered to structural T1-images (6). Perfusion data were extracted from 9 regions-of-interest (ROIs), normalized to white matter, and statistically compared between carriers and non-carriers. The Montreal Brain Template defined the 9 ROIs, which were preselected based on the previous studies of structural changes: including frontal, temporal, parietal, and occipital lobes, hippocampus, basal ganglia and cerebellum. Data were normalized to white matter in order to smooth inter-individual differences. We included 8 carriers and 7 first-degree related family non-carriers. Comparing carriers with non-carriers, the former showed decreased mean CBF values at the capillary level in all ROIs, with significant changes in capillary CBF in the parietal (mean change 14 %; p = 0.03) and occipital (mean change 9 %; p = 0.02) lobes. Decreased cerebral blood flow can be measured in presymptomatic CHMP2B mutation carriers with statistically significant differences in the occipital- and parietal lobes. Alterations in CBF possibly affect the whole brain. Data indicate that FTD-3 pathology might involve brain capillaries. This may impact the understanding of the pathogenesis involving endosomal dysfunction and implicates involvement of the vasculature in FTD-3 pathobiology. References: 1) Nature Genetics 2005; 37:806-8. 2) Neurology 2002; 59:1585-94. 3) JNEN 2003; 33: 884-91. 4) NeuroImage 2009; 45: 713-21. 5) Dement Geriatr Cogn Disord 2009;27:182-6. 6) Brain Warping Ed. A W Toga 1999;133-42.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".