Cognitive and Functional Decline and their Relationship in Patients with Mild Alzheimer’s Disease (P3.208)
Bibliographic record
Abstract
OBJECTIVE: This post-hoc analysis assesses the relationship between cognitive and functional impairment in mild Alzheimer’s disease (AD) patients participating in 18-month clinical trials. BACKGROUND: In patients with AD, the relationship between cognitive and functional progression is not fully understood; however, functional decline has been postulated to follow cognitive decline. DESIGN/METHODS: Data of patients with mild AD (Mini-Mental State Examination score 20 to 26) were pooled from two multicenter, double-blind, Phase 3 studies (EXPEDITION and EXPEDITION2). Patients were randomized to infusions of 400-mg solanezumab (N=654), a monoclonal antibody binding soluble amyloid beta, or placebo (N=660) every 4 weeks for 18 months. Cognitive and functional outcome measures were assessed using the AD Assessment Scale-Cognitive subscale (ADAS-Cog) and the AD Cooperative Study-Activities of Daily Living (ADCS-ADL). Analyses included comparisons among the normalized scales, correlations between outcome measures, and path analyses to model the relationship of treatment effect on cognition and function. RESULTS: In placebo-treated patients, normalized ADAS-Cog and ADCS-ADL scales showed that cognitive impairment may precede functional impairment. Additionally, the correlation between cognition and function increased over time (Spearman rank correlation = -0.34 at baseline to -0.62 after 18 months, p<0.001 for both). Solanezumab-treated patients exhibited a 34% reduction in cognitive decline (p=0.001) and an 18% reduction in functional decline (p=.045) compared with placebo-treated patients after 18 months. Path analyses demonstrated that 87% of the treatment effect on function was driven by the treatment effect on cognition, with the remaining 13% due to direct treatment effect. CONCLUSIONS: Findings from this study are consistent with the hypothesis that functional impairment is primarily related to and follows cognitive decline. The increasing correlation between cognition and function over time suggests that as cognition worsens, function is more directly affected. The cognitive treatment effect appeared to explain the majority of the functional treatment effect. Study Supported by: Eli Lilly and Company
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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 | 0.003 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| 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) | 0.002 | 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".