Figure 2: Symptomatic stages of Alzheimer’s disease according the NIA-AA research framework.

The schematic shows the symptomatic stages of disease in Alzheimer’s disease according to the NIA-AA research framework⁴⁵ of Alzheimer’s disease. The stages apply only to individuals who are in the Alzheimer’s disease continuum, which is defined by biomarker evidence of amyloid pathology with or without tau pathology, and is irrespective of the status of neurodegeneration. The colour scheme indicates the continuous progression of cognitive impairment in an individual, from no objective cognitive impairment (light green) to severe objective cognitive impairment (dark red). According to the framework, there are six stages of symptomatic manifestation of Alzheimer’s disease. Stage 1 is the fully asymptomatic disease stage. Stage 2, also known as the transitional stage, includes individuals showing the first subtle signs of Alzheimer’s disease, manifesting as a combination of one or more of the following symptoms: subjective cognitive decline, subtle objective decline, or mild behavioural symptoms. Stage 1 and stage 2 are classified as preclinical Alzheimer’s disease, according to the 2011 NIA-AA criteria.⁴⁴ Stage 3 reflects, in principle, mild cognitive impairment, whereas stages 4 reflects mild dementia, stage 5 reflects moderate dementia, and stage 6 reflects severe dementia. NIA-AA=National Institute of Aging-Alzheimer’s Association.