RESUMO
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 (Aß) 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 (Aß42/40, 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 (ß 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.
RESUMO
Several lines of evidence have indicated that depression might be a prodromal symptom of Alzheimer's disease (AD). This systematic review and meta-analysis investigated the cross-sectional association between amyloid-beta, one of the key pathologies defining AD, and depression or depressive symptoms in older adults without dementia. A systematic search in PubMed yielded 689 peer-reviewed articles. After full-text screening, nine CSF studies, 11 PET studies, and five plasma studies were included. No association between amyloid-beta and depression or depressive symptoms were found using cerebrospinal fluid (CSF) (0.15; 95% CI: -0.08; 0.37), positron emission topography (PET) (Cohen's d: 0.09; 95% CI: -0.05; 0.24), or plasma (-0.01; 95% CI: -0.23; 0.22). However, subgroup analyses revealed an association in plasma studies of individuals with cognitive impairment. A trend of an association was found in the studies using CSF and PET. This systematic review and meta-analysis suggested that depressive symptoms may be part of the prodromal stage of dementia.
