Letter to the Editor about Dynamic patterns of depression and their association with stroke: insights from CHARLS, ELSA, and HRS

Dear Editor, We read with great interest the study that examined the association between long-term patterns of depressive symptoms and future stroke risk in older adults, using data from three large cohort studies in China, the United Kingdom, and the United States1. The authors are to be commended for moving beyond a single-point assessment of depression and instead focusing on changes in depressive symptoms over time. This approach better reflects real-world experiences of depression and offers meaningful insights for stroke prevention. A major strength of the study lies in its use of repeated assessments of depressive symptoms and its cross-national comparison. By showing that individuals with persistently high or worsening depressive symptoms had a higher risk of stroke across all three cohorts, the study supports the idea that long-standing mental health problems may have serious physical health consequences. The consistency of these findings across countries adds credibility to the overall conclusions. Nevertheless, several issues merit further discussion. The study was also reported in accordance with the TITAN guidelines, which further strengthens the transparency and rigor of its design and reporting2. First, the way depressive symptom “trajectories” were defined may oversimplify the true patterns of depression in older adults. Individuals whose symptoms fluctuated over time (for example, improvement followed by relapse) were excluded from the analysis. Such patterns are common in clinical practice, and excluding these participants may limit the generalizability of the findings to the broader older population. Second, depressive symptoms were classified only as “present” or “absent,” without accounting for differences in symptom severity. This binary approach may underestimate the impact of mild to moderate depression. Depression is not an all-or-nothing condition, and future studies that consider symptom severity rather than relying on a simple threshold may yield more nuanced insights. Third, stroke outcomes were mainly based on self-reported physician diagnoses (entirely so in HRS and ELSA, and partially in CHARLS through linkage with medical records). Validation studies suggest that self-reported stroke has a false-positive rate of 25–37%, with substantial false negatives as well, influenced by recall bias, cognitive function, and cultural factors3,4. These issues may be particularly pronounced in older cohorts, especially given the close relationship between depressive symptoms and cognitive decline, potentially inflating the observed association between depressive trajectories and “stroke.” In addition, differences in outcome verification across cohorts (with partial validation only in CHARLS) further weaken the reliability of pooled comparisons. Fourth, the study used logistic regression to estimate the risk of stroke “occurrence,” even though stroke is a time-dependent event during follow-up and the number of events was relatively small (133–376 cases). Logistic regression ignores the timing of events and censoring, which may lead to biased estimates in longitudinal cohort studies. Standard practice would favor Cox proportional hazards models or other survival analysis methods to appropriately handle time-to-event data. Existing methodological guidelines caution that ignoring time information can underestimate or distort risk associations5. Finally, although the authors adjusted for several confounders (such as age, sex, hypertension, and diabetes), potential reverse causation and unmeasured confounding shared by depression and stroke were not fully addressed. These include more detailed assessment of prior depression history, stroke subtypes, inflammatory markers, and social support. Subgroup analyses suggested heterogeneity (for example, by rural versus urban residence and by sex), but limited sample sizes reduced statistical power, and multiple comparisons raise the possibility of false-positive findings. While the results suggest that certain groups (such as women, rural residents, and individuals without hypertension) may be more vulnerable to the effects of long-term depression, these findings should be interpreted with caution, as the number of stroke cases in some subgroups was small and estimates may be unstable. In summary, this study provides important evidence that persistent or worsening depressive symptoms are associated with an increased risk of stroke in later life. At the same time, simplifying complex depressive patterns and excluding individuals with fluctuating symptoms may limit the broader applicability of the conclusions. Despite these limitations, the study underscores the importance of ongoing monitoring of mental health in older adults and supports the integration of mental health care into stroke prevention strategies. Ethical approval Not applicable.