Table 3.

Numeric clinical stages of individuals on the Alzheimer continuum, examples of the clinical assessments that would be used to characterize the participants in a clinical trial, and corresponding ATN characteristics at each stage. The Neurological Clinical Staging is consistent with the recent FDA guidance of AD stages (U.S. Food and Drug Administration. Early Alzheimer’s disease: developing drugs for treatment; draft guidance for industry. Federal Register; 2018. p. 7060-1).

Numeric Clinical Staging	Clinical Phase	Cognitive/ Composite Assessment	Functional Assessment	Behavioral Assessment	ATN Classification
1	Cognitively normal with no indication of decline	PACC; APCC	No functional deficit	No established behavioral change	A+T-N-
2	Cognitively normal with indication of decline	PACC; APCC	No functional deficit	No established behavioral change	A+T+N- or A+T+N+
3	Prodromal AD	CDR-sb; ADCOMS; iADRS; NTB	ADCS-ADL (MCI version)	MBI/NPI	A+T+N+
4	Mild AD dementia	ADAS-cog; NTB; CDR-sb	ADCS-ADL	NPI	A+T+N+
5	Moderate AD dementia	ADAS-cog; NTB; CDR-sb	ADCS-ADL	NPI	A+T+N+
6	Severe AD dementia	SIB; CDR-sb	ADCS-ADL (severe version)	NPI	A+T+N+

A – amyloid; ADAS-cog – Alzheimer’s Disease Assessment Scale – cognitive subscale; ADCOMS - AD Composite Score; ADCS-ADL (MCI) – Alzheimer’s Disease Cooperative Study – Activities of Daily Living scale (mild cognitive impairment version); APCC - Alzheimer Prevention Initiative Cognitive Composite; CDR-sb - Clinical Dementia Rating- Sum of Boxes; iADRS - Integrated AD Rating Scale; MBI – Minimal Behavioral Impairment scale; N – neurodegeneration; NPI – Neuropsychiatric Inventory; NTB - Neuropsychological Test Battery; PACC - Preclinical Alzheimer Cognitive Composite; SIB – severe impairment battery; T - tau