Depression trajectories, genetic risk, and cognitive performance in older adults: multilevel model with a 10-year longitudinal cohort

Background: Cognitive performance in older ages is strongly affected by individuals' genetic predispositions. We investigated whether depression trajectories were associated with subsequent cognitive performance independent of participants' genetic predispositions.Methods: Participants from the Health and Retirement Study with European ancestry and aged over 50 were included in the analysis. Depressive symptoms were evaluated using the Center for Epidemiologic Studies Depression Scale, and the 6-year trajectories were fitted using latent class linear mixed models. Linear multilevel regression was applied to model the associations between depression trajectory and subsequent cognitive performance. Stratified analyses were performed to investigate these associations in participants with different genetic predispositions of cognitive performance and APOE epsilon 4 allelic status.Results: A total of 5942 eligible participants were included in the study. Four depression trajectories were identified. Compared with the non-depression trajectory, all other depression trajectories were associated with worse cognitive performance (beta [95% CI]: mild-depression trajectory: -0.20 [-0.56, -0.06], p = 0.007; worsening-depression trajectory: -0.29 [-0.47, -0.12], p = 0.001; persistent-depression trajectory: -0.32 [-0.53, -0.13], p = 0.001). Although these associations were independent of participants' inherent genetic risk, the participants with a low polygenetic score for cognitive performance were more likely to have an enhanced association between depression trajectories and cognitive decline. Similar relationships were also found in APOE epsilon 4 noncarriers.Conclusion: Among older participants with European ancestry, even a mild-depression trajectory was associated with worse cognitive performance. Early intervention in participants with any degree of depression might benefit regarding preventing cognitive performance decline.