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Hypothetical model of biomarker changes and proposed new clinical staging of AD. Accumulation of Aβ and subsequent manifestation of tau-mediated neurotoxicity begin roughly 10–20 years prior to the onset of dementia. MCI due to AD is a prodromal phase of AD, i.e., an intermediate phase between normal cognitive functioning and dementia. Preclinical AD is a stage earlier than MCI in which cognitive function is normal but the presence of amyloid pathology is suggested by biomarkers.
