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

Abstract

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. 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. 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. 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.