Temporal Relationship Between Depressive Symptoms and Cognition in Mid and Late Life: A Longitudinal Cohort Study

Objectives: To examine the bidirectional temporal relationship between depressive symptoms and cognition in relation to risk, reaction, and prodrome. Design: Cross-lag analysis of longitudinal data collected online at baseline and 12-month follow-up. Setting and participants: A United Kingdom population cohort of 11,855 participants aged 50 years and over. Measures: Patient Health Questionnaire-9 (depressive symptoms), cognitive measures: Paired Associate Learning, Verbal Reasoning, Spatial Working Memory, and Digit Span. Results: Depressive symptoms predicted a decline in paired associates learning [β = -.020, P = .013, (95% confidence interval [CI], ‒.036, -.004)] and verbal reasoning [β = -.014, P = .016, (95% CI ‒.025, -.003)] but not vice versa. Depressive symptoms predicted [β = -.043, P < .001, (95% CI ‒.060, -.026); β = -.029, P < .001, (95% CI ‒.043, -.015)] and were predicted by [β = -.030, P = < .001, (95% CI ‒.047, -.014); β = -.025, P = .003, (95% CI ‒.041, -.009)], a decline in spatial working memory and verbal digit span, respectively. Conclusions and implications: Depressive symptoms may be either a risk factor or prodrome for cognitive decline. In addition, a decline in attention predicts depressive symptoms. Clinical implications and implications for further research are discussed.This article represents independent research funded by the National Institute for Health Research (NIHR) Biomedical Research Center at South London and Maudsley NHS Foundation Trust and King's College London. This research was also supported by the NIHR Collaboration for Leadership in Applied Health Research and Care South West Peninsula and the NIHR Exeter Clinical Research Facility.Published version, accepted version (12 month embargo), submitted versio