Wessels · Neurology. Clinical practice 2023 · narrative review · n=?

Meaningful Clinical Changes in Alzheimer Disease Measured With the iADRS and Illustrated Using the Donanemab TRAILBLAZER-ALZ Study Findings.

Cited 36 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review and methodological commentary interpreting phase 2 trial data

PubMed 36891463 · doi:10.1212/CPJ.0000000000200127 · record verified 2026-08-29

What was done

The authors reviewed the background, structure, and clinical interpretation of the Integrated Alzheimer's Disease Rating Scale (iADRS)—a composite cognitive and functional trial endpoint—using data from the phase 2 TRAILBLAZER-ALZ randomized trial of donanemab in early symptomatic Alzheimer disease over 76 weeks.

What was found

In the TRAILBLAZER-ALZ study, donanemab slowed disease progression measured by the iADRS by 32% at 18 months compared with placebo (p = 0.04). Applying thresholds for clinically meaningful decline, treatment with donanemab was estimated to delay reaching that threshold by approximately 6 months.

Why it matters

This commentary outlines how composite endpoints like the iADRS can capture combined cognitive and functional trajectories and translate statistical slowing into estimated delays in clinical worsening.

Limits

This is a narrative review and methodological explanation rather than a primary trial report or systematic review. The abstract provides no sample size, confidence intervals, or safety outcomes, and relies on findings from a single phase 2 trial.

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