The role of Alzheimer’s disease pathology in frontotemporal dementia related syndromes
Bibliographic record
Abstract
Abstract Background Corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP) are two syndromes associated with frontotemporal lobar degeneration (FTLD) with heterogeneous presentation and progression. Co‐pathology of FTLD and Alzheimer’s disease (AD) has been described and could influence the clinical presentation of CBS and PSP. The goal of this study is to evaluate the role of AD pathology in CBS and PSP, by analyzing functional and structural neuroimaging and memory performance. Method Patients with a clinical diagnosis of PSP and CBS (n=15) and AD (n=18) underwent functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI). Patients were separated according to AD biomarker positivity (CBS‐PSP‐AD, n=6) and negativity (CBS‐PSP‐noAD, n=9) based on the presence of AD biomarkers in cerebrospinal fluid. FMRI images were preprocessed to assess connectivity differences in the default mode network (DMN). DTI was analyzed to trace the bilateral superior longitudinal fasciculus (SLF) and extract its fractional anisotropy and mean diffusivity. Verbal learning and memory were assessed with the California Verbal Learning Test (CVLT‐II) and the Consortium to Establish a Registry for Alzheimer’s disease (CERAD) of the Toronto Cognitive Assessment, and the z‐scores were compared between groups. Result The DMN showed reduced functional connectivity in the groups with AD biomarker positivity (CBS‐PSP‐AD and AD patients) relative to the CBS‐PSP‐noAD group. Specifically, reduced connectivity was observed between the left angular gyrus and the left (T(23) = ‐4.02, p‐FDR= 0.02) and right (T(23) = ‐3.48, p‐FDR=0.04) lateral parietal regions in AD vs CBS‐PSP‐noAD. Reduced connectivity was found between the left angular gyrus, the posterior cingulate cortex (T(11) = ‐4.72, p‐FDR=0.02) and the right hippocampus (T(11) = ‐3.94, p‐FDR=0.04) in CBS‐PSP‐AD vs CBS‐PSP‐noAD. No differences were found in DMN connectivity in AD vs CBS‐PSP‐AD. SLF tractography metrics showed no difference between groups. Both CBS‐PSP‐AD and AD patients had significantly worse delayed memory scores than the CBS‐PSP‐noAD group (post‐hoc p‐FDR=0.01). Conclusion There are similarities between AD positive biomarker groups (CBS‐PSP‐AD and AD patients) in functional connectivity and memory scores, with these groups differing from the CBS‐PSP‐noAD patients. These results suggest that pathology can mediate functional connectivity patterns and influence clinical manifestation.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.001 | 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".