Differential cognitive correlates of tau and neurofilament light chain in cerebrospinal fluid of frontotemporal lobar degeneration patients with and without Alzheimer’s markers
Bibliographic record
Abstract
Abstract Background Frontotemporal lobar degeneration (FTLD) phenotypes can be associated with Alzheimer’s disease (AD). It is unknown whether differences exist in relationship between markers of degeneration such as tau and neurofilament light chain (NFL) and cognition between FTLD with and without AD. Method 40 FTLD patients were included in this study: (A) 31 FTLD without AD [5 behavioral variant FTD, 11 corticobasal syndrome (CBS), 1 non‐fluent variant primary progressive aphasia (nfvPPA), 12 progressive supranuclear palsy (PSP), 2 semantic variant PPA (svPPA); age (67.74±10.28); sex (20M:11F)]; and (B) 9 FTLD positive for AD [6 CBS‐AD, 1 nfvPPA‐AD, 1 PSP‐AD, 1 svPPA‐AD; age (66±8.46); sex (5M:4F)]. CSF levels of Aβ42, phosphorylated tau (p‐tau) & total tau (t‐tau) were measured using sandwich ELISA and AD pathology was deemed present if p‐tau > 68 pg/mL and Aβ42 to t‐tau index < 0.8. CSF NFL was measured using SIMOA. Full neuropsychological battery was completed, controlled for age/education. Result In the FTLD cohort, significant relationships were observed between CSF t‐tau and CDR sum of boxes (r=0.599, p=.001) and MOCA (r=‐0.530, p=.004). In FTLD group, digit span backwards (DSB) was significantly associated with CSF t‐tau (r=‐0.492, p=.009) & NFL (r=‐0.427, p=.02); while verbal fluency, Trail Making Test part A & digit span forward (DSF) were only related to NFL (r=‐0.410, p=.03; r=0.463, p=.02; r=‐0.374, p=.05, respectively). In the FTLD‐AD cohort, MOCA was significantly associated with CSF p‐tau (r=‐1.00, p<.0001) & t‐tau (r=‐0.887, p=.02); memory and executive function tests including California verbal learning test 30s recall, DSB & DSF were significantly associated with CSF t‐tau (r=‐0.788, p=.04; r=‐0.836, p=.04; r=‐0.760, p=.07, respectively); while verbal fluency & category fluency were significantly associated with CSF markers of NFL (r=‐0.841, p=.04; r=‐1.00, p<.0001), p‐tau (r=‐0.981, p<.001; r=‐1.00, p<.0001), & t‐tau (r=‐0.984, p<.001; r=‐0.977, p=.004). Conclusion In both FTLD with and without AD, overall severity was related to CSF t‐tau but executive function in FTLD without AD was related to CSF NFL while in FTLD‐AD it was related to p‐tau and t‐tau. The presence of AD in FTLD phenotypes alters relationship to NFL, which may be indicative of differences in extent of degeneration.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".