Effects of Cholinesterase Inhibitor Medication on QTc Interval in Memory Clinic Patients

Background: Cholinesterase inhibitors (ChEIs)—donepezil, rivastigmine, and galantamine—are beneficial in treating Alzheimer disease (AD). However, due to their impact on extra-cerebral acetylcholine signaling, concerns about cardiac adverse effects, including QT interval prolongation, persist. Despite this, evidence-based guidelines for electrocardiogram (ECG) monitoring during ChEI treatment are lacking, and prior studies on ChEIs and corrected QT intervals (QTc) yield inconsistent findings. Objective: This study aimed to investigate the association between ChEI use and changes in QTc intervals among older adults. Methods: We collected retrospective data from first-time visitors to the geriatric memory clinic of Turku City Hospital in 2017 and 2019. We included patients who were newly prescribed ChEIs and had ECG data available (n = 126, mean age 81.1 years, 56.3% female). QTc prolongation was defined as ≥460 ms in females and ≥450 ms in men. Paired t tests compared QTc means before and during ChEI use, and McNemar tests analyzed changes in the proportion of prolonged QTc. Results: Mean ± SD QTc (ms) before versus during ChEI use was: 420.8 ± 24.0 versus 423.9 ± 28.0 (P = .13) for donepezil; 416.0 ± 20.4 versus 416.5 ± 26.1 (P = .92) for galantamine; 416.1 ± 22.3 versus 409.6 ± 20.1 (P = .30) for rivastigmine; and 419.7 ± 23.4 versus 421.5 ± 27.3 (P = .34) for all ChEIs. Prolonged QTc occurred in 7.9% of patients before versus 12.7% during ChEI use (P = .21). Conclusion and Relevance: We found no statistically significant association between ChEI use and QTc interval prolongation or an increased proportion of pathological QTc values during ChEI treatment. Larger studies are warranted to establish evidence-based recommendations on ECG monitoring during ChEI medication.