Type: Clinician-administered cognitive outcome measure
Purpose: Quantify cognitive function in Alzheimer's disease clinical trials
Developer: Rosen, Mohs, and Davis (1984)[1]
Current use: Primary endpoint in LY-3372689 MAGNOLIA trial, Phase 3 anti-amyloid trials (Aducanumab), and most AD therapeutic trials
The Alzheimer's Disease Assessment Scale — Cognitive Subscale (ADAS-Cog) is the gold-standard cognitive outcome measure in Alzheimer's disease clinical trials. It was developed in 1984 by Rosen et al. as a comprehensive assessment tool specifically for AD trials[1:1]. The scale measures multiple domains of cognition including memory, language, praxis, and visuospatial function.
ADAS-Cog has become the most widely used primary endpoint in AD drug trials, with a large body of validation data across diverse populations. Its sensitivity to change over time and ability to distinguish between AD patients and healthy controls has made it the benchmark for regulatory approval studies[2].
The original 11-item version contains:
Maximum score: 70 (higher = more impairment)
Adds two items to improve sensitivity:
Maximum score: 85
Further additions:
Maximum score: 90
| Domain | Items | Max Points | Description |
|---|---|---|---|
| Memory | Word recall, recognition | 25 | Immediate and delayed verbal memory |
| Language | Naming, commands, comprehension, speech | 25 | Verbal abilities and comprehension |
| Praxis | Constructional, ideational | 10 | Visuospatial and motor execution |
| Orientation | Time, place | 8 | Temporal and spatial awareness |
| Concentration | Number cancellation | 5 | Attention and processing speed |
The MAGNOLIA trial (NCT05063565) used ADAS-Cog 13 as the primary efficacy endpoint[3]:
| Trial | Drug | Primary Endpoint | Result |
|---|---|---|---|
| Aducanumab EMERIAN | Aducanumab | ADAS-Cog 13 | Mixed (high-dose showed slowing) |
| ENGAGE | Aducanumab | ADAS-Cog 13 | Did not meet primary |
| CLARITY AD | Lecanemab | ADAS-Cog 14 | -27% slowing at 18 months |
| TRAILBLAZER-ALZ | Donanemab | ADAS-Cog 13 | Met primary endpoint |
| MAGNOLIA | LY-3372689 | ADAS-Cog 13 | Pending (expected Q3 2026) |
ADAS-Cog is typically used alongside:
The OGA inhibitor therapeutic approach targets tau hyperphosphorylation by increasing O-GlcNAcylation on tau proteins. This is based on the Yin-Yang Hypothesis — that O-GlcNAcylation and phosphorylation compete for the same serine/threonine sites on tau.
If OGA inhibition successfully reduces tau phosphorylation:
The key question in MAGNOLIA is whether sufficient target engagement (CSF O-GlcNAc increase) translates into measurable cognitive benefit at 18 months — a question that will inform the entire OGA inhibitor field.
Rosen, W. G., Mohs, R. C., Davis, K. L. A new rating scale for Alzheimer's disease. American Journal of Psychiatry. 1984. ↩︎ ↩︎
Mohs, R. C., et al. Development of cognitive instruments for use in clinical trials of antidementia drugs. Alzheimer Disease and Associated Disorders. 2000. ↩︎
Kaye, S. D., et al. LY3372689 MAGNOLIA trial primary endpoint design. Journal of Prevention of Alzheimer's Disease. 2024. ↩︎