Table 1 FDA-proposed stages for drug development vis-à-vis the preclinical AD, MCI due to AD, and AD dementia phases of AD proposed by NIA-AA
AD stage | Clinical/biomarker presentation | Cognitive and functional assessment | AD clinical continuum correlate |
|---|---|---|---|
1 | No cognitive impairment, including no subjective complaints, but AD pathology is present | No detectable abnormalities with sensitive neuropsychological measures | Preclinical |
2 | Transitional cognitive change from individual baseline, with cognition remaining within normal bounds and no functional impairment AD pathology is present | Detectable change on sensitive neuropsychological measures or subjective report of change | Preclinical |
3 | Subtle or more apparent objective cognitive impairment Impairment in ability to perform instrumental activities of daily living No loss of independence AD pathology is present | Detectable abnormalities on sensitive neuropsychological measures; mild but detectable functional impairments on sensitive measures | MCI due to AD |
4 | From 4 to 6, gradual progression on levels of cognitive impairment; impact on ability to perform basic activities of daily living and loss of independence AD pathology is present | Detectable abnormalities on COAs of cognition and function | Mild AD dementia |
5 | Moderate AD dementia | ||
6 | Severe AD dementia |