Electrocardiogram differences in cognitively unimpaired PSEN1‐E280A carriers and non‐carriers from the Alzheimer’s Prevention Initiative Autosomal‐Dominant Alzheimer’s Disease Colombia Trial

Abstract

AbstractBackgroundSome but not all studies have found compromised myocardial function and amyloid deposition, related or unrelated to amyloid‐β pathology itself, in persons with late‐onset Alzheimer’s Disease (AD). Other changes in QT interval, heart rate variability, and QRS voltages have been described in the electrocardiogram (ECG), but those are not consistent between studies. We explored differences in several ECG measures in cognitively unimpaired (CU) Presenilin 1 (PSEN1)‐E280A carriers and non‐carriers from the Alzheimer’s Prevention Initiative Autosomal Dominant AD (API ADAD) Trial (NCT01998841).MethodThe trial enrolled 252 CU 30–60‐year‐old participants. We included participants (144 PSEN1‐E280A mutation carriers and 71 non‐carriers) in these analyses who were enrolled in the trial during their first screening attempt. Baseline cardiovascular data and medical history were obtained by medical assessment and blood sample. Interval durations, QRS voltages of all leads, and the diagnosis were taken from baseline ECG. T‐test, chi‐square, correlation, and effect size were used in the data analysis. The p values in this are exploratory.ResultMean age (years) for carriers was 36 and 43 for non‐carriers. Years of education, sex, and clinical variables like body mass index, cholesterol, hemoglobin A1c, TSH, and previous cardiovascular disorders were similar between groups. There were no differences in the heart rate, PR, QRS, or corrected QT interval duration. Voltages in AVL and DI leads were lower in carriers than non‐carriers with a low size of effect (0.42 vs. 0.50, p = 0.03; 0.64 vs. 0.71, p = 0.04, respectively), while the other ten leads and low voltage in any of the 12 derivates did not show any difference. There was also a negative and small correlation between voltage and age for DII, V6, and AVR (‐0.146, ‐0.144, ‐0.137; p = 0.03,0.03,0.04; respectively).ConclusionOur findings suggest no clinically significant difference in ECG parameters between PSEN1‐E280A mutation carriers compared to non‐carriers. Since intramyocardial deposits of amyloid‐β are age‐dependent, it is likely that there are low levels of these deposits in young CU individuals. Longitudinal studies with larger samples that include CU patients might identify ECG‐related changes associated with amyloid‐β cardiac deposits.