Mediation Analysis for Sparse and Irregularly Spaced Longitudinal Outcomes with Application to the MrOS Sleep Study

Abstract: Mediation analysis has become a widely used method for identifying the pathways through which an independent variable influences a dependent variable via intermediate mediators. However, limited research addresses the case where mediators are high-dimensional and the outcome is represented by sparse, irregularly spaced longitudinal data. To address these challenges, we propose a mediation analysis approach for scalar exposures, high-dimensional mediators, and sparse longitudinal outcomes. This approach effectively identifies significant mediators by addressing two key issues: (i) the underlying correlation structure within the sparse and irregular cognitive measurements, and (ii) adjusting mediation effects to handle the high-dimensional set of candidate mediators. In the MrOS Sleep study, our primary objective is to explore lipid pathways that may mediate the relationship between rest-activity rhythms and longitudinal cognitive decline in older men. Our findings suggest a potential mechanism involving rest-activity rhythms, lipid metabolites, and cognitive decline, and highlight significant mediators identified through multiple testing procedures.