The meta-memory ratio: a new cohort-independent way to measure cognitive awareness in asymptomatic individuals at risk for Alzheimer\u2019s disease

Geoffroy Gagliardi,Marion Houot,Federica Cacciamani,Stéphane Epelbaum,Marie-Odile Habert,Bruno Dubois

doi:10.1186/s13195-020-00626-1

Abstract

BackgroundLack 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.MethodFour 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.ResultIn 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.ConclusionThis nonlinear evolution of ACD in very early AD must be taken into account in clinical care and for trial enrollment as well.

Highlights

It is well known that the first brain changes due to Alzheimer’s disease (AD), the first lesions, and in particular amyloid aggregation, appear several decades before the clinical diagnosis of dementia [1,2,3]
This nonlinear evolution of awareness of cognitive decline (ACD) in very early AD must be taken into account in clinical care and for trial enrollment as well
Using the patient-informant discrepancy in asymptomatic at risks for AD subjects, we found that a higher level of AD biomarkers in cognitively normal (CN) individuals was related to a low ACD [25]

Summary

Introduction

It is well known that the first brain changes due to Alzheimer’s disease (AD), the first lesions, and in particular amyloid aggregation, appear several decades before the clinical diagnosis of dementia [1,2,3] In this preclinical phase, the accumulation of such lesions is accompanied by a subtle decline in cognitive domains, including executive functioning and memory [1, 4,5,6,7,8]. There are at least three major ways to evaluate anosognosia in the literature [22,23,24]: (i) clinician rating of awareness, (ii) patient-informant discrepancy, and (iii) discrepancy between subjective and objective cognitive measures In these methods, anosognosia would be defined as a gap between the subject’s perception of his/her own performance (overestimation) and a control measure (i.e., the clinician’s/caregiver’s rating of cognitive decline or the objective cognitive performance). We introduced a meta-memory ratio (MMR) and explored how it is associated with neuroimaging AD biomarkers in asymptomatic individuals at risk for AD

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