Subjective cognitive decline (SCD) may be the first sign of Alzheimer's disease (AD), but it can also reflect other pathologies such as cerebrovascular disease or conditions like depressive symptomatology. The role of depressive symptomatology in SCD is controversial. We investigated the association between depressive symptomatology, cerebrovascular disease, and SCD. We recruited 225 cognitively unimpaired individuals from a prospective community-based study [mean age (SD) = 54.64 (10.18); age range 35–77 years; 55% women; 123 individuals with one or more subjective cognitive complaints, 102 individuals with zero complaints]. SCD was assessed with a scale of 9 memory and non-memory subjective complaints. Depressive symptomatology was assessed with established questionnaires. Cerebrovascular disease was assessed with magnetic resonance imaging markers of white matter signal abnormalities (WMSA) and mean diffusivity (MD). We combined correlation, multiple regression, and mediation analyses to investigate the association between depressive symptomatology, cerebrovascular disease, and SCD. We found that SCD was associated with more cerebrovascular disease, older age, and increased depressive symptomatology. In turn, depressive symptomatology was not associated with cerebrovascular disease. Variability in MD was mediated by WMSA burden, presumably reflecting cerebrovascular disease. We conclude that, in our community-based cohort, depressive symptomatology is associated with SCD but not with cerebrovascular disease. In addition, depressive symptomatology did not influence the association between cerebrovascular disease and SCD. We suggest that therapeutic interventions for depressive symptomatology could alleviate the psychological burden of negative emotions in people with SCD, and intervening on vascular risk factors to reduce cerebrovascular disease should be tested as an opportunity to minimize neurodegeneration in SCD individuals from the community.

Background Subjective cognitive decline (SCD) may be the first sign of Alzheimer’s disease (AD), but it can also reflect other pathologies such as cerebrovascular disease or conditions like depressive symptomatology. The role of depressive symptomatology in SCD is controversial. In this study, we investigated the association between depressive symptomatology, cerebrovascular disease, and SCD. We hypothesized three different scenarios, where depressive symptomatology would co‐exist, contribute to, or be a consequence of SCD (Figure). Method We recruited 225 cognitively unimpaired individuals from a prospective community‐based study (mean age (SD) = 54.64 (10.18); age range 35 – 77 years; 55% women; 102 individuals without any subjective cognitive complaint, 123 individuals with one or more complaints). SCD was assessed with a scale of 9 memory and non‐memory subjective complaints. Depressive symptomatology was assessed with established questionnaires. We used magnetic resonance imaging markers of white matter signal abnormalities (WMSA) and mean diffusivity (MD) to assess cerebrovascular disease. We combined correlation, multiple regression, and mediation analyses to investigate the association between depressive symptomatology, cerebrovascular disease, and SCD. Results We found that SCD was associated with higher cerebrovascular disease (WMSA: r=0.210, p<0.002; MD: r=0.216, p=0.001), older age (r=0.373, p<0.001), and increased depressive symptomatology (r=0.340, p<0.001). In turn, depressive symptomatology was not associated with cerebrovascular disease (WMSA: r=0.003, p<0.961; MD: r=0.076, p<0.321) or age (r=0.069, p<0.030). We also studied whether abnormalities in white matter MD in SCD may be due to cerebrovascular disease. Results showed that variability in MD was mediated by WMSA burden (p=0.026), presumably reflecting cerebrovascular disease. Conclusion In our community‐based cohort, depressive symptomatology co‐exists with SCD and reflects emotional factors, but does not reflect cerebrovascular disease. In addition, depressive symptomatology did not influence the capacity of SCD to predict underlying cerebrovascular disease. We suggest that therapeutic interventions for depressive symptomatology could alleviate the psychological burden of negative emotions in people with SCD, and intervening on vascular risk factors to reduce cerebrovascular disease should be tested as an opportunity to minimize neurodegeneration in SCD.