The meta-memory ratio: a new cohort-independent way to measure cognitive awareness in asymptomatic individuals at risk for Alzheimer's disease.

Lack of awareness of cognitive decline (ACD) has been described at the preclinical and prodromal stages of Alzheimer’s disease (AD). In this study, we introduced a meta-memory ratio (MMR) and explored how it is associated with neuroimaging AD biomarkers in asymptomatic individuals at risk for AD. Four hundred forty-eight cognitively healthy participants from two cohorts of subjective memory complainers (INSIGHT-PreAD and ADNI) were included. Regression models were used to assess the impact of AD biomarkers on the MMR. In both cohorts, there was a significant quadratic effect of cerebral amyloidosis on the MMR value. In particular, participants had a high ACD up to the amyloid positivity threshold, above which a decrease of ACD was eventually observed as the amyloid load increased. This nonlinear evolution of ACD in very early AD must be taken into account in clinical care and for trial enrollment as well.