These results support a biphasic model of changes in AD, which could affect the selection of patients for clinical trials and the use of magnetic resonance imaging as a surrogate marker of disease modification.

Self-perceived cognitive decline, measured by the SCD-Q part I (MyCog), discriminated SCD from CTR. Part II (TheirCog) was strongly related to subjects' objective cognitive performance, and discriminated between subjects with or without cognitive impairment. The SCD-Q is a useful tool to measure self-perceived cognitive decline incorporating the decliner and the informant perspective.

Our data suggest that interactions between biomarkers in AD result in a 2-phase phenomenon of pathological cortical thickening associated with low CSF Aβ, followed by atrophy once CSF p-tau becomes abnormal. These interactions should be considered in clinical trials in preclinical AD, both when selecting patients and when using MRI as a surrogate marker of efficacy.