SCD-plus features and AD biomarkers in cognitively unimpaired samples: A meta-analytic approach for nine cohort studies

Introduction: Specific features of subjective cognitive decline (SCD-plus) have been proposed to indicate an increased risk of preclinical Alzheimer's disease (AD). However, few studies have examined how these features relate to AD biomarkers in cognitively unimpaired (CU) older adults.

Methods: Meta-analyses were performed using cross-sectional data from nine cohorts (n = 7219, mean age (SD): 71.17 (5.9), 56.5% female) to determine associations of SCD-plus features with positron emission tomography (PET)- or cerebrospinal fluid (CSF)-derived amyloid beta (Aβ) and tau biomarkers.

Results: Participants with preclinical AD (community-based only) were more likely to fulfill SCD-plus features. The presence of self-reported memory decline, associated concern/worry, and a higher number of fulfilled features were all associated with high Aβ levels. Only the latter was associated with abnormal tau.

Discussion: Simultaneous endorsement of multiple SCD-plus features is a robust indicator of abnormal AD biomarkers in CU older adults, whereas isolated SCD features seem only sensitive to elevated Aβ, supporting their value as early behavioral markers of preclinical AD.

Highlights: About two-tenths of our sample had abnormal amyloid beta (Aβ) levels with evidence of subjective cognitive decline (SCD). Preclinical AD subsamples (community-based) had a higher percentage of participants meeting SCD-plus features. Self-reported memory decline and concern/worry were the sole features associated with high Aβ, but not tau, burden. A higher number of fulfilled SCD-plus features are linked to high Aβ and tau burden. Use of multiple SCD-plus features may help identify early stages of biological AD.