Depressive symptoms and plasma AT(N) biomarkers among cognitively healthy and mild cognitively impaired in a diverse cohort.

Depression is a known risk factor for dementia and MCI, but its associations with AT(N) biomarkers remain inconsistent and may differ by cognitive status. We cross-sectionally studied 2929 dementia-free participants from the Health & Aging Brain Study-Health Disparities (HABS-HD). Mild cognitive impairment (MCI) was identified as having cognitive complaints, Clinical Dementia Rating scores between 0.5 and 2.0, and at least one cognitive test ≤ 1.5 SD below norms. We defined AT (N) with plasma biomarkers amyloid-β 42/40 (Aβ42/40), phosphorylated tau (p-tau181), neurofilament light (NfL), assessed using SIMOA technology and magnetic resonance imaging (MRI) based Alzheimer disease (AD) signature cortical thickness. Depressive symptoms were measured with the Geriatric Depression Scale (GDS), categorized as high (≥10) or low (<10). We used linear regression to determine association between depressive symptoms and biomarkers, adjusting for age, sex, education, kidney function, and body mass index. High depressive symptoms (19 %) were linked to higher NfL (standardized mean differences [SMD] = 0.10, 95 % confidence interval [CI: 0.02-0.18] and p-tau181 (SMD = 0.15, 95 % CI: 0.07-0.22) levels compared to low symptoms but not with Aβ42/40 or AD cortical thickness. Participants with both MCI and high depressive symptoms had higher NfL (SMD = 0.19, 95 % CI: 0.05-0.33) and p-tau181 (SMD = 0.30, 95 % CI: 0.16-0.45), and lower AD signature cortical thickness (SMD = -0.30, 95 % CI: -0.48 to -0.11). No group differences were found for Aβ42/40. Depressive symptoms, particularly among those with MCI, were linked to greater tau and neurodegeneration; longitudinal studies are needed to clarify this clinical significance.