Alzheimer's & Dementia · Nov 9, 2026

Comparative functional and cognitive trajectories following second‐generation antipsychotic initiation among long‐term care residents with Alzheimer disease: A target trial emulation study

By Jiang C, Krivinko J, Sweet RA et al.

Introduction: Real‐world evidence comparing the functional and cognitive outcomes associated with commonly prescribed second‐generation antipsychotics (SGAs) in long‐term care (LTC) residents with Alzheimer disease (AD) is limited. Methods: We emulated target trials using linked LTC Data Cooperative and Medicare data. A total of 17,766 eligible new users initiating risperidone, quetiapine, olanzapine, or aripiprazole were compared under an intention‐to‐treat framework using inverse probability of treatment weighting and weighted generalized estimating equations. Outcomes were 12‐month trajectories of Activities of Daily Living (ADL) and Brief Interview for Mental Status (BIMS). Results: ADL trajectories were similar across SGAs. In BIMS trajectory, quetiapine was associated with a modestly greater decline ( β = −0.203, 95% confidence interval [CI] −0.380 to −0.027) compared with aripiprazole. Age modified several comparative treatment effects, particularly for BIMS. Findings were consistent across sensitivity analyses. Discussion: Long‐term functional and cognitive outcomes were broadly comparable across commonly prescribed SGAs. Age‐related heterogeneity in comparative treatment effects warrants further investigation.

doi.org/10.1002/trc2.70347 Open access PubMed 43005395 Interventions