Cognitive Evolution in Tysabri (natalizumab)-Treated Multiple Sclerosis Patients (P4.171)
Bibliographic record
Abstract
OBJECTIVE: The objectives are to understand the impact of natalizumab on cognition beyond two years of therapy and to investigate whether baseline characteristics are predictive of clinical response. BACKGROUND: Cognitive dysfunction affects 40-60% of MS patients and progresses over time. Its presence is a major predictor of further deterioration in the short term. Natalizumab has shown to be superior to placebo in preserving cognitive function for the first two years of therapy. DESIGN/METHODS: This is a single-center, 24-month, observational study. Sixty-three patients treated with natalizumab were assessed prior to monthly infusions using the CogState battery and the SDMT. The Beck depression questionnaire (BDI-II) was also administered at baseline and every 4th month prior to infusion. Patient demographics, MS treatment history, EDSS, MSSS, and natalizumab treatment duration were collected at baseline. Patients with cognitive impairment from other causes (i.e., depression; >18 on BDI-II) were excluded. A linear mixed model was conducted with time on natalizumab (4 years, n=12) as a between-subjects factor, time point as a within-subjects factor, and age, EDSS, type of MS and number of prior drug treatments as covariates. The current data are from the 12-month interim analysis. RESULTS: Irrespective of time on natalizumab, significant improvements were observed at the group level in executive function (p<.0001), verbal memory (p<.0001), and working memory (p<.0001), whereas processing speed (p=.19) and attention (p=.15) remain unchanged. Only one patient had clinically meaningful decline, defined as a decline of 1 or more standard deviations over three consecutive months on two or more CogState tests (comprised of Detection, Identification or One Back tests), perhaps due to recent family crisis and/or acute depression. CONCLUSIONS: Interim analysis suggests that natalizumab can preserve and even improve cognitive function beyond two years of continuous therapy. More conclusions will be drawn when final results are available. Study Supported by: an unrestricted grant from Biogenidec
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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 | 0.001 |
| 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".