IWG — Diagnosis Recommended Algorithm

The same biomarker profile does not have the same diagnostic meaning across clinical syndromes. Biomarker positivity must always be interpreted in the context of the clinical phenotype.

Hover over any cell to see the recommended further investigations.

Highly probable – established

Probable

Possible

Unlikely

Highly unlikely – excluded

Non-assessable

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	Common AD phenotypes amnestic · logopenic PPA · posterior cortical atrophy	Uncommon AD phenotypes behavioural/dysexecutive · corticobasal · non-fluent PPA · semantic variant PPA	Other phenotypes dementia with Lewy bodies · Richardson · Huntington · ALS
A+T+	Highly probable – established Further investigationNone required.	Probable Further investigationNone required; careful follow-up needed — an incongruent clinical phenotype and neurodegeneration pattern should trigger a new investigation.	Unlikely Further investigationFull investigation of cause.
A+T?	Probable Further investigationConsider a tau measure (PET, CSF).	Possible Further investigationConsider a tau measure (PET, CSF).	Unlikely Further investigationFull investigation of cause.
A+T−	Probable Further investigationConsider an additional tau measure (PET, CSF).	Possible Further investigationConsider an additional tau measure (PET, CSF).	Unlikely Further investigationFull investigation of cause.
A?T+	Possible Further investigationConsider an amyloid measure (PET, CSF).	Unlikely Further investigationFull investigation of cause and consider an amyloid measure (PET, CSF).	Unlikely Further investigationFull investigation of cause.
A−T+	Possible Further investigationConsider an additional amyloid measure (PET, CSF).	Unlikely Further investigationFull investigation of cause.	Unlikely Further investigationFull investigation of cause.
A−T?	Unlikely Further investigationFull investigation of cause and consider a tau measure (PET, CSF).	Highly unlikely – excluded Further investigationFull investigation of cause.	Highly unlikely – excluded Further investigationFull investigation of cause.
A?T−	Unlikely Further investigationFull investigation of cause and consider an amyloid measure (PET, CSF).	Highly unlikely – excluded Further investigationFull investigation of cause.	Highly unlikely – excluded Further investigationFull investigation of cause.
A−T−	Highly unlikely – excluded Further investigationFull investigation of cause.	Highly unlikely – excluded Further investigationFull investigation of cause.	Highly unlikely – excluded Further investigationFull investigation of cause.
A?T?	Non-assessable Further investigationConsider tau and amyloid measures (PET, CSF).	Non-assessable Further investigationFull investigation of cause and consider tau and amyloid measures (PET, CSF).	Highly unlikely – excluded Further investigationFull investigation of cause.

Why this matters

The same A+ T+ biomarker profile yields a Highly probable diagnosis of Alzheimer disease in a patient presenting with an amnestic syndrome — but only an Unlikely diagnosis in a patient with a Richardson syndrome or dementia with Lewy bodies.

This is the core IWG position: biomarkers are necessary but not sufficient. The clinical phenotype determines the diagnostic weight of any biomarker result.

Source: Dubois B, Villain N, Frisoni GB, et al. Clinical diagnosis of Alzheimer's disease: recommendations of the International Working Group. Lancet Neurology. 2021; Table 2 — Alzheimer's disease diagnosis in a clinical setting. · ⬇ Download PDF · View on Lancet →