Changes in the awareness of cognitive decline across the course of Alzheimer’s disease: Comparison of two assessment methods

Abstract

AbstractBackgroundRecent studies have suggested that poor awareness of cognitive decline (ACD) could be an early indicator of Alzheimer's disease (AD). However, there is still no gold‐standard for ACD assessment. In this study, we describe longitudinal changes in ACD in subjects with biomarker‐defined AD (according to the A/T/N framework by Jack and colleagues), assessing ACD by two methods: a subject‐informant discrepancy and a subjective‐objective scores discrepancy.MethodWe included 334 amyloid‐ and tau‐positive (A+T+) subjects with normal cognition, MCI and dementia, and 137 cognitively‐normal A‐T‐ controls from the ADNI cohort, followed up for an average of 5 years. Using a statistical mixed‐effects model (Couronné & al., 2019, ISBI), we reconstructed the evolution of a composite memory score, self and informant’s assessments of cognitive functioning (E‐Cog) and two ACD measures: the ACD index (ACDI, i.e. the difference between E‐Cog‐Subject and E‐Cog‐Informant) and the Meta‐Memory Ratio (MMR, Gagliardi et al. 2019 ART, i.e. the comparison between the E‐Cog‐Subject and a composite memory score). After rescaling the scores, an abnormality threshold was calculated for each of them corresponding to the 95th percentile of the distribution of control subjects.ResultThe subject perceives, at the beginning of the disease, a cognitive decline that is not detected neither by the informant (Figure 1) nor by the tests (Figure 2). This condition can be called "hypernosognosia". The subjective cognitive decline increased slightly and became abnormal 2 years after the diagnosis of dementia. A clear anosognosia was visible starting from the MCI phase using both assessment methods. The MMR detected a reduction in ACD earlier than the ACDI: the subject passes from a hypernosognosia to a good match with the memory score between 64 and 69 years, and with the informant rating between 73 and 76 years on average.ConclusionHypernosognosia is associated with a risk of AD during a short period of time, when the disease is at a very early stage. Thereafter, the individual's ACD decreases. We will discuss the advantages and disadvantages of both assessment methods in both research and clinical practice, especially in relation to their usefulness for early detection of AD.