Uncovering the Role of Neuropsychiatric Symptoms in Cognitive Impairment Progression

With the growing prevalence of cognitive impairment, early detection has become increasingly critical. Prior studies have examined the association between neuropsychiatric symptoms (NPS) and cognitive impairment, identifying potential predictive relationships. However, they hardly evaluated the heterogeneous relationships between serial patterns of NPS and evolving cognition status of the patients. To address this limitation, we investigate the statistical causal relationship between NPS and cognitive impairment, as well as the dynamic changes in their predictive effects over time, with a specific focus on sex differences. Our approach accounts for the fluctuating nature of NPS and varying follow-up durations across participants by implementing a bootstrap strategy that repeatedly samples a fixed number of visits per participant in a temporal order. Then, we apply causal discovery techniques and counterfactual framework-based causal inference methods to estimate the independent effects of NPS over time. Our findings highlight apathy as a key predictive symptom of cognitive impairment. Moreover, its predictive effect peaks earlier in females than in males, indicating that early-stage tracking is particularly informative in female participants. This suggests sex-specific monitoring strategies may improve early detection and intervention of cognitive impairment.