What is iADRS, and how is it different from CDR-SB?

What it is

iADRS - the Integrated Alzheimer's Disease Rating Scale - is a composite cognitive-and-functional endpoint used in late-stage Alzheimer's clinical trials. It produces a single number by combining two sub-scores:

• The cognitive sub-score - derived from the Alzheimer's Disease Assessment Scale, cognitive subscale (ADAS-Cog), a structured cognitive battery covering memory, language, praxis, and orientation tasks.
• The functional sub-score - derived from the Alzheimer's Disease Cooperative Study - instrumental Activities of Daily Living scale (ADCS-iADL), a caregiver-completed questionnaire about how independently the patient is handling activities like managing finances, preparing meals, or using transportation.

The two sub-scores are combined into a single iADRS value, with higher scores corresponding to better cognitive and functional performance - note this is the opposite direction from CDR-SB, where higher means worse. A treatment effect on iADRS shows up as a smaller decrease in the score over the trial period for the treatment arm relative to the placebo arm.

How it differs from CDR-SB

CDR-SB - Clinical Dementia Rating, Sum of Boxes - is the other dominant primary endpoint in contemporary late-stage Alzheimer's trials. The two scales answer related but slightly different questions.

• CDR-SB is scored by a clinician based on a structured interview with the patient and a knowledgeable informant. It assesses global staging across six broad domains (memory, orientation, judgment, community affairs, home and hobbies, personal care) and produces a number on a 0–18 scale. It is sensitive to change in early symptomatic populations and is the primary endpoint that has been used in the lecanemab pivotal trial and several other late-stage programs.

• iADRS combines a cognitive test that the patient sits and completes with the clinician (ADAS-Cog) and a functional questionnaire completed by the caregiver (ADCS-iADL). It produces a number on a different scale - the exact range depends on the version of the components used - with higher scores indicating better function. It was the primary endpoint in the TRAILBLAZER-ALZ 2 trial of donanemab.

Both scales are valid measures of cognitive and functional change. They tend to show similar treatment-effect directions in the same trial when both are reported, but they emphasise different things. CDR-SB is heavier on what a clinician judges from a structured conversation. iADRS is heavier on what a patient can perform on a structured cognitive task plus what a caregiver describes about daily independence.

Why two scales coexist in the field

The simplest answer is historical: different trial sponsors made different choices when designing their pivotal programs, and both choices were defensible. The FDA has accepted both endpoints as primary measures of clinical efficacy in early Alzheimer's disease.

The deeper answer is that there is no single canonical scale that captures everything the field cares about. CDR-SB has the advantage of being widely understood, easily comparable across trials, and well-validated against clinical staging. iADRS has the advantage of separating the cognitive component from the functional component cleanly, with the cognitive component being a directly performed test rather than a clinician judgment.

In practice, late-stage trials increasingly report both - one as primary and one as secondary, or both as co-primaries - so that readers can compare across programs.

How to read a readout that uses iADRS

Three things to look at:

• The absolute change. What was the iADRS change over the trial duration in the placebo arm, and how much smaller was the iADRS change in the treatment arm? A smaller decrease (or, equivalently, a larger preservation of score) is the treatment-effect direction.
• The relative slowing. Many readouts will frame the result as a percentage slowing of decline. As with CDR-SB, this framing makes a small absolute difference look larger; both numbers are valid and answer different questions.
• The component split. Because iADRS breaks down into a cognitive sub-score and a functional sub-score, well-designed readouts will report whether the treatment effect was concentrated in one of those sub-scores or distributed across both. A meaningful effect that shows up in both sub-scores is generally read as more clinically convincing than an effect that shows up only in one.

Our Signal on the CDR-SB clinical-meaningfulness debate covers the broader interpretive question of how to read small differences on cognitive and functional scales, which applies to iADRS as well.

What it cannot tell you

• Biological change. Like CDR-SB, iADRS is a clinical scale. For evidence of underlying biological treatment effect, the field uses amyloid PET and tau PET.
• Symptom-specific changes. iADRS captures cognitive and functional domains at a composite level. It is not designed to measure changes in behavioural symptoms, sleep, mood, or quality-of-life measures specifically.
• Individual prognosis. iADRS is a population-level endpoint. A specific patient's trajectory cannot be read directly from a group-level iADRS delta in a trial.

Why it keeps coming up

Every late-stage Alzheimer's readout in this era will report at least one of CDR-SB or iADRS - and often both. Knowing which scale a trial used, what the absolute and relative changes were, and how the components broke down is the first thing to know about the result. For the broader reference context of all the endpoints in current use, see our snapshot of clinical trial endpoints.

This page is a plain-language primer. It is not medical advice.