Long-term patterns of depressive symptoms and cognitive aging in middle-aged and older adults

BACKGROUND: Although depressive symptoms have been associated with subsequent cognitive outcomes, it remains unclear whether different long-term symptom patterns are linked to specific cognitive domains such as episodic memory and orientation. METHODS: We analyzed 7,211 participants from the China Health and Retirement Longitudinal Study (CHARLS). Based on a prespecified rule-based approach using CES-D-10 depressive symptom scores from 2011 to 2015, participants were categorized into four symptom pattern groups: never depressed, early-remission, late-onset, or persistent/recurrent. Linear regression was used to evaluate associations between these patterns and 2018 cognitive outcomes, adjusting for baseline cognition and potential confounders. Subgroup, sensitivity, and directional analyses were conducted to evaluate consistency and temporal direction. An exploratory pathway analysis examined whether grip strength and sleep disturbance might partly account for the association between the persistent/recurrent depressive symptom pattern and episodic memory. External validation was conducted using data from the Health and Retirement Study (HRS). RESULTS: Compared with the never depressed group, the late-onset and persistent/recurrent depressive symptom patterns were associated with lower 2018 episodic memory (adjusted coefficients: -0.932 [95% CI, - 1.227 to - 0.637] and - 0.842 [- 1.104 to - 0.580], respectively), whereas associations for the early-remission pattern were weaker. For orientation, significant associations were observed only for the late-onset and persistent/recurrent depressive symptom patterns. Associations were stronger among women and those with lower educational attainment. In an exploratory pathway analysis (n = 5,721), lower grip strength and greater sleep disturbance partly explained the association between the persistent/recurrent depressive symptom pattern and episodic memory (estimated indirect contribution: 16.9%). Directional analyses suggested potential bidirectionality between depressive symptoms and episodic memory. External validation in the HRS showed associations in the same direction. CONCLUSIONS: Persistent/recurrent and late-onset depressive symptom patterns were associated with poorer subsequent cognitive outcomes, particularly among women and individuals with lower educational attainment. Lower grip strength and more severe sleep disturbance may partly account for the association between the persistent/recurrent depressive symptom pattern and episodic memory. Directional analyses also indicated a bidirectional interplay between depressive symptoms and cognitive outcomes. Our findings suggest that long-term monitoring of depressive symptom patterns, together with attention to physical function and sleep health, may help identify individuals at elevated risk of cognitive decline.