(B-156) Motor Vehicle Crash Risk in Older Adults with Alzheimer’s Disease After Acetylcholinesterase Inhibitor Initiation: A Sequential Target Trial Emulation

Background: Acetylcholinesterase inhibitors (ACheIs) provide modest symptomatic benefits for cognitive function in mild-to-moderate Alzheimer’s disease (AD). Their impact on motor vehicle crashes (MVCs) has not been evaluated, despite AD causing attention, perception, and executive function deficits that may impair driving.

Objectives: To compare the one-year MVC risk in older adults with mild-to-moderate AD who initiated ACheIs vs. those who did not.

Methods: We defined a hypothetical target trial and emulated it using administrative data. We used New Jersey drivers’ licensing and police-reported MVC data linked to Medicare fee-for-service claims from January 1, 2008 through January 1, 2017. To increase sample size, we conducted 470 sequential emulations, each beginning on a consecutive calendar week, allowing eligible individuals to participate in multiple emulations (unit of analysis: “person-trials”). We identified community-dwelling adults 66 years or older with an active New Jersey driver’s license and mild-to-moderate AD. We used the one-year Bynum Standard algorithm to identify individuals with AD and a cutoff of < 0.280 for the Claims-Based Frailty Index to classify mild-to-moderate AD severity. At the start of each week, we identified if ACheIs (donepezil, galantamine, rivastigmine, or tacrine) were initiated within seven days after a ≥97-day washout. We excluded individuals who had a MVC or used ACheIs in the year prior to follow-up. Out of 2,429,408 eligible person-trials with an active license, mild-to-moderate AD, and continuous one-year Medicare enrollment, 444,507 remained in the analysis. Follow-up lasted until MVC, death, loss to follow-up, or one year, whichever occurred first. We computed cumulative incidence of MVCs using Kaplan-Meier curves.

Results: Of 444,507 included person-trials, 1,804 (0.4%) initiated ACheIs. Initiators were more often Hispanic (6.5% vs. 5.2%) and female (54.9% vs. 52.1%) than non-initiators, and had more preventive healthcare visits (≥3 visits: 19.6% vs. 18.8%). Non-initiators had higher Combined Comorbidity Scores (mean [SD]: 4.6 [3.3] vs. 3.9 [3.0]) and more hospitalizations (49.2% vs. 36.0%). We observed 191 (10.6%) initiators and 44,376 (10.0%) non-initiators with an MVC over one year of follow-up. More non-initiators died (7.3% vs. 6.4%) and were lost to follow-up (6.4% vs. 5.3%).

Conclusions: Our findings suggest no notable difference in one-year MVC risk by ACheI initiation status. Ongoing analyses will account for baseline covariate differences, censoring, and potential immortal time bias to refine our estimates of MVC risk for older adults with mild-to-moderate AD using ACheIs.