Long-term antipsychotic use and cognitive decline in community-dwelling older adults with mild–moderate Alzheimer disease: Data from NILVAD

Abstract

Introduction: Previous evidence has suggested that antipsychotic use may be associated with accelerated cognitive decline in those living with dementia. However, the cognitive effects of long-term antipsychotic use in community-dwelling older adults with mild–moderate Alzheimer disease (AD) has not been explored to date. Methods: We assessed the impact of long-term antipsychotic use on the rate of cognitive decline (Alzheimer’s Disease Assessment Scale—Cognitive Subsection) and dementia progression (Clinical Dementia Rating—Sum of Boxes [CDR-Sb]/Disability Assessment for Dementia [DAD]) over 18 months in older adults with mild–moderate AD. Results: Of 509 participants with mild–moderate AD, one-tenth (54/509; 10.6%) were prescribed an antipsychotic for the 18-month study duration. Antipsychotic use was significantly associated with accelerated cognitive decline at both 12 (β: 3.53, 0.91–6.17, p = 0.008) and 18 months (β: 3.81, 0.49–7.14, p = 0.024) in addition to greater dementia progression at both 12 (β: 1.85, −0.97–2.73, p < 0.001 for CDR-Sb/β: −3.33, −5.56–1.10, p = 0.003 for DAD) and 18 months (β: 1.41, 0.16–2.67, p = 0.027 for CDR-Sb/β: −3.86, −6.64 to −1.08, p = 0.006 for DAD). APOE ε4 carriers experienced significantly greater cognitive decline with long-term antipsychotic use. Conclusions: Long-term antipsychotic use was associated with greater cognitive decline and dementia progression in community-dwelling older adults with mild–moderate AD. Our findings are consistent with previous evidence encouraging cautious and careful consideration of risks versus benefits of antipsychotic usage in those with AD.