The Meta-Memory Ratio: A new cohort-independent way to measure cognitive awareness in asymptomatic individuals at risk for Alzheimer’s disease

Abstract

Background: Lack of Awareness for 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.Method: 448 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.Result: 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. Conclusion: This nonlinear evolution of ACD in very early AD must be taken into account in clinical care and for trial enrollment as well.