1. Depressive Symptoms and Plasma Markers of Alzheimer's Disease and Neurodegeneration: A Coordinated Meta-Analysis of 8 Cohort Studies.
- Author
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Twait EL, Kamarioti M, Verberk IMW, Teunissen CE, Nooyens ACJ, Monique Verschuren WM, Visser PJ, Huisman M, Kok AAL, Eline Slagboom P, Beekman M, Vojinovic D, Lakenberg N, Arfan Ikram M, Schuurmans IK, Wolters FJ, Moonen JEF, Gerritsen L, van der Flier WM, and Geerlings MI
- Subjects
- Humans, Aged, Amyloid beta-Peptides blood, Cohort Studies, Female, Male, Netherlands epidemiology, Neurofilament Proteins blood, Apolipoprotein E4 genetics, Apolipoprotein E4 blood, Alzheimer Disease blood, Alzheimer Disease genetics, Alzheimer Disease epidemiology, Biomarkers blood, Depression blood, Depression epidemiology, tau Proteins blood
- Abstract
Background: Depressive symptoms are associated with an increased risk of Alzheimer's disease (AD). There has been a recent emergence in plasma biomarkers for AD pathophysiology, such as amyloid-beta (Aβ) and phosphorylated tau (p-tau), as well as for axonal damage (neurofilament light, NfL) and astrocytic activation (glial fibrillary acidic protein, GFAP). Hypothesizing that depressive symptoms may occur along the AD process, we investigated associations between plasma biomarkers of AD with depressive symptoms in individuals without dementia., Methods: A two-stage meta-analysis was performed on 2 clinic-based and 6 population-based cohorts (N = 7210) as part of the Netherlands Consortium of Dementia Cohorts. Plasma markers (Aβ42/40, p-tau181, NfL, and GFAP) were measured using Single Molecular Array (Simoa; Quanterix) assays. Depressive symptoms were measured with validated questionnaires. We estimated the cross-sectional association of each standardized plasma marker (determinants) with standardized depressive symptoms (outcome) using linear regressions, correcting for age, sex, education, and APOE ε4 allele presence, as well as subgrouping by sex and APOE ε4 allele. Effect estimates were entered into a random-effects meta-analysis., Results: Mean age of participants was 71 years. The prevalence of clinically relevant depressive symptoms ranged from 1% to 22%. None of the plasma markers were associated with depressive symptoms in the meta-analyses. However, NfL was associated with depressive symptoms only in APOE ε4 carriers (β 0.11; 95% CI: 0.05-0.17)., Conclusions: Late-life depressive symptoms did not show an association to plasma biomarkers of AD pathology. However, in APOE ε4 allele carriers, a more profound role of neurodegeneration was suggested with depressive symptoms., Competing Interests: DISCLOSURES No disclosures to report., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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