Associations between antipsychotics exposure and dementia risk: A prospective cohort study of 415,100 participants

Antipsychotics (APs) are among the most widely prescribed medications, and have been shown to cause cognitive decline. But previous studies on their effects on dementia risk are controversial and scarce. We aimed to examine the relationships of APs exposure with the risk of dementia. Data were obtained from a prospective cohort of 415,100 UK Biobank (UKB) participants. We investigated the effects of APs exposure and their various classes on dementia risk by using multivariable Cox proportional hazard models and further the dose-response effects of oral APs. After a mean follow-up of 8.64 years, 5235 (1.3 %) participants developed all-cause dementia (ACD), among whom 2313 (0.6 %) developed Alzheimer's disease (AD), and 1213 (0.3 %) developed vascular dementia (VaD). Exposure to any APs conferred increased risks of ACD (HR: 1.33, 95 % CI = 1.17–1.51, P < 0.001) and VaD (HR: 1.90, 95 % CI = 1.51–2.40, P < 0.001), but not AD (HR: 1.22, 95 % CI = 1.00–1.48, P = 0.051). Cumulative dose-response relationships of oral APs with the risks of ACD and VaD were observed (P for trend, P < 0.05). Our study is observational and does not show evidence of causality. Since there are relatively few cases of dementia in the UKB, APs exposure may be higher than estimated in our study. APs exposure increased the risk of developing dementia. Dose-response relationships were found between oral APs and dementia risk. Efforts to raise awareness of doctors and patients about this potential drug-related risk are critical to reducing APs use.