Abstract
BACKGROUND: Subjective Cognitive Decline (SCD) may represent the initial symptom of Alzheimer’s disease (AD), but SCD may be absent and/or unrelated to actual cognitive decline. Objective Subtle Cognitive Decline (obj‐SCD) can be identified through longitudinal standardized neuropsychological tests in individuals not yet meeting criteria for Mild Cognitive Impairment (MCI). We argue that the relationship between SCD and obj‐SCD might help to inform clinical and research criteria in pre‐MCI stages. This study explores the dyadic perception (participant‐informant) of SCD as an early symptomatic marker of obj‐SCD in Cognitively Unimpaired (CU) population at increased risk of (AD) dementia. METHOD: Three hundred thirty‐seven CU participants from the ALFA+ prospective cohort study (with three‐year follow‐up) were included. AT(N) profiles were defined at baseline with Cerebrospinal Fluid (CSF) biomarkers. Baseline reports of SCD, “My‐Cognition” for the participant and “Their‐Cognition” for the informant, were measured with the SCD‐Questionnaire (SCD‐Q). AD biomarker‐based reliable change indices adjusted for practice effect (A‐T‐[N]‐ group’s longitudinal performance as reference) were computed for the robust measurement of cognitive trajectory. Considering the relationship between the number of neuropsychological measures and the base rate of impaired scores, obj‐SCD was defined as longitudinal biomarker‐based performance below ‐1.645 SD (<5(th)‐percentile) in at least 3 variables within each domain (episodic memory | global). Episodic memory and global obj‐SCD were analyzed using logistic linear regression with CSF Aβ42/40 status and SCD reports as predictors. RESULT: CSF Aβ‐status was not associated with global, but with memory obj‐SCD (OR = 2.743, 95%CI = 1.013‐7.811). SCD scores in My‐Cognition and Their‐Cognition were associated with global obj‐SCD (OR = 1.096, 95%CI = 1.003‐1.192; OR = 1.228, 95%CI = 1.075‐1.394), and Their‐Cognition was further associated with memory obj‐SCD (OR = 1.183, 95%CI = 1.020‐1.354). Descriptives in Table‐1, inferential results in Table‐2 and Figure‐1. CONCLUSION: Aβ‐pathology was linked to memory, but not global obj‐SCD, in participants not yet meeting MCI criteria. Subjective reports from informants showed greater effect sizes than reports from participants and were associated to memory and global obj‐SCD. The participant‐informant discrepancy observed for memory obj‐SCD and its association to AD‐related impairment suggested that participants with objective memory problems might not be fully aware of these subtle changes, highlighting the relevance of tracking dyadic reports in preclinical Alzheimer’s.