Delirium event and associated treatment modifications among older adults with Alzheimer's disease: An interrupted time-series analysis of Medicare data

Background: Both Alzheimer's disease (AD) and deliriogenic medications increase the risk of delirium in older adults. This study examined the association between delirium and the subsequent monthly use of anticholinergic, sedative, and opioid medications in the 1 year after delirium in older adults with AD. Methods: This comparative interrupted time series analysis involved adults (aged 65 years and older) with a diagnosis of AD initiating on cholinesterase inhibitors (ChEIs) based on 2013-2017 Medicare data. Separate patient- level segmented regression models were used for each outcome to evaluate changes in the cumulative anticholinergic burden (CAB), sedative load, and opioid load after the delirium/index event using a 12- month baseline and follow- up period among patients who had a delirium event and those without delirium (control group). Propensity score- based stabilized weights were utilized to balance baseline factors in the delirium and control groups. Results: The study included 80,019 older adults with AD with incident ChEI use; 17.11% had delirium. There was an immediate decline in monthly CAB after the delirium event (mean estimate -0.86, p- value: 0.01) compared to the control group. A similar decline was observed when examining the sedative load (-0.06, p- value: 0.002) after the delirium event. However, there was no decline in opioid load (-0.50, p-value: 0.18). In the long term, CAB (0.13; p-value: <0.0001), sedative load (0.01; p-value: <0.001), and opioid load (0.07; p- value: 0.006) increased over the 1- year post- delirium period in the delirium group compared to those without delirium. Conclusion: This study found the burden of deliriogenic medications over the 1- year follow- up showed increasing trends in older adults with AD, even though there was some level shift in CAB and sedative load after the delirium event.