Staging of Alzheimer's disease: past, present, and future perspectives.

For many years Alzheimer's disease (AD) was associated with the dementia stage of the disease, the tail end of a pathophysiological process that lasts approximately two decades. Whereas early disease staging assessments focused on progressive deterioration of clinical functioning, brain imaging with positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarker studies highlighted the long preclinical phase of AD in which a cascade of detectable biological abnormalities precede cognitive decline. The recent proliferation of imaging and fluid biomarkers of AD pathophysiology provide an opportunity for the identification of several biological stages in the preclinical phase of AD. We discuss the use of clinical and biomarker information in past, present, and future staging of AD. We highlight potential applications of PET, CSF, and plasma biomarkers for staging AD severity in vivo.