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

BACKGROUND: 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. AIM: 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." METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.