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

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.

This study aimed to investigate the association between ChEI use and changes in QTc intervals among older adults.

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.

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).

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.