Clinical Manifestations.

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-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.