Multidimensional Depressive Symptom Exposure and Incident Cognitive Decline: A Prospective Cohort Study

Despite being a modifiable risk factor for cognitive decline, the influence of depressive symptoms on cognitive decline lacks a systematic assessment of its cumulative exposure intensity, temporal dimensions, and dynamic change.

To systematically evaluate the multidimensional associations of depressive symptom exposure-including cumulative exposure, burden, duration, and dynamic change patterns-with incident cognitive decline, by adopting an analytical framework that integrates "static accumulation and dynamic evolution."

Among 8847 Health and Retirement Study (HRS) participants free of cognitive decline at baseline, cumulative depressive symptoms were quantified as the area under the curve (AUC) across 2012-2016 waves. A cut-point was identified by maximizing the log-rank statistic for cognitive decline risk within a clinically relevant range (2.5-3.5) and used to define cumulative burden and high-exposure duration. Dynamic symptom patterns across three waves were identified, and their interaction with cumulative burden was examined. Multivariable Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for incident cognitive decline risk associated with these exposure metrics.

During 3.67 median follow-up years, 2311 incident cognitive decline cases occurred. Cognitive decline risk rose with escalating cumulative depressive exposure: the highest tertile (HR 1.42; 1.28-1.58), cumulative burden ≥0 (HR 1.34; 1.21-1.49), longest duration (HR 1.29; 1.12-1.48), and a progressively worsening trend (HR 1.52; 1.25-1.84) all significantly increased risk.

Our findings demonstrate that the effect of depressive symptoms on cognitive decline is cumulative, time-dependent, and dynamic. These results emphasize that sustaining a stable, low-severity depressive symptom profile is essential for lifelong cognitive health.