Characterizing the Clinical Features and Atrophy Patterns of <i>MAPT</i> -Related Frontotemporal Dementia With Disease Progression Modeling
Bibliographic record
Abstract
<h3>Background and Objective</h3> Mutations in the <i>MAPT</i> gene cause frontotemporal dementia (FTD). Most previous studies investigating the neuroanatomical signature of <i>MAPT</i> mutations have grouped all different mutations together and shown an association with focal atrophy of the temporal lobe. The variability in atrophy patterns between each particular <i>MAPT</i> mutation is less well-characterized. We aimed to investigate whether there were distinct groups of <i>MAPT</i> mutation carriers based on their neuroanatomical signature. <h3>Methods</h3> We applied Subtype and Stage Inference (SuStaIn), an unsupervised machine learning technique that identifies groups of individuals with distinct progression patterns, to characterize patterns of regional atrophy in <i>MAPT-</i>associated FTD within the Genetic FTD Initiative (GENFI) cohort study. <h3>Results</h3> Eighty-two <i>MAPT</i> mutation carriers were analyzed, the majority of whom had P301L, IVS10+16, or R406W mutations, along with 48 healthy noncarriers. SuStaIn identified 2 groups of <i>MAPT</i> mutation carriers with distinct atrophy patterns: a temporal subtype, in which atrophy was most prominent in the hippocampus, amygdala, temporal cortex, and insula; and a frontotemporal subtype, in which atrophy was more localized to the lateral temporal lobe and anterior insula, as well as the orbitofrontal and ventromedial prefrontal cortex and anterior cingulate. There was one-to-one mapping between IVS10+16 and R406W mutations and the temporal subtype and near one-to-one mapping between P301L mutations and the frontotemporal subtype. There were differences in clinical symptoms and neuropsychological test scores between subtypes: the temporal subtype was associated with amnestic symptoms, whereas the frontotemporal subtype was associated with executive dysfunction. <h3>Conclusion</h3> Our results demonstrate that different <i>MAPT</i> mutations give rise to distinct atrophy patterns and clinical phenotype, providing insights into the underlying disease biology and potential utility for patient stratification in therapeutic trials.
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 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 | 0.001 |
| 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".