Semiparametric Models for Practice Effects in Longitudinal Cognitive Trajectories: Application to an Aging Cohort Study

Abstract: Background: True cognitive longitudinal decline can be obscured by repeated testing, which is called practice effects (PEs). We developed a modeling framework that aligns participants by baseline and estimates visit-specific PEs independently of age-related change. Method: Using real data ($N=175$), we estimated within-subject correlations via linear mixed-effects modeling and applied these parameters to simulate longitudinal trajectories for healthy controls (HC) and individuals with schizophrenia (SZ). Simulations incorporated aging, diagnostic differences, and cumulative PE indicators. Generalized estimating equations (GEEs) were fit with and without PEs to compare model performance. Results: Models that ignored PEs inflated estimates of cognitive stability and attenuated HC--SZ group differences. Including visit-specific PEs improved recovery of true trajectories and more accurately distinguished aging effects from learning-related gains. Interaction models further identified that PEs may differ by diagnosis or by age at baseline. Conclusion: Practice effects meaningfully bias longitudinal estimates if left unmodeled. The proposed alignment-based GEE framework provides a principled method to estimate PEs and improves accuracy in both simulated and real-world settings. Keywords: practice effects; repeat testing; serial testing; longitudinal testing; mild cognitive impairment; cognitive change.