Association of Depressive Symptoms and Cognition in Older Adults Without Dementia Across Different Biomarker Profiles

Background: Depression is a late-life risk factor for cognitive decline. Evidence suggests an association between Alzheimer's disease (AD) associated pathologic changes and depressive symptoms. Objective: To investigate the influence of AT(N) biomarker profile (amyloid-β [A], p-tau [T], and neurodegeneration [N]) and gender on cross-sectional associations between subclinical depressive symptoms and cognitive function among older adults without dementia. Methods: Participants included 868 individuals without dementia from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Depressive symptoms were measured using the Geriatric Depression Scale (GDS). ADNI neuropsychological composite scores assessed memory and executive function (EF). PET, cerebrospinal fluid, and MRI modalities classified the study sample into biomarker profiles: normal biomarkers (A-T-N-), AD continuum (A+T±N±), and suspect non-AD pathology (SNAP; A-T±N-or A-T-N±). Multivariate regression models were used to investigate associations between GDS and cognitive domains. Results: GDS was negatively associated with memory (β= -0.156, p < 0.001) and EF (β= -0.147, p < 0.001) in the whole sample. When classified by biomarker profile, GDS was negatively associated with memory and EF in AD continuum (memory: β= -0.174, p < 0.001; EF: β= -0.129 p = 0.003) and SNAP (memory: β= -0.172, p = 0.005; EF: β= -0.197, p = 0.001) subgroups. When stratified by sex, GDS was negatively associated with memory (β= -0.227, p < 0.001) and EF (β= -0.205, p < 0.001) in men only. Conclusion: The association between subclinical depressive symptoms and cognitive function is highly influenced by the AT(N) biomarker profile.