Ventricular electrocardiographic signatures associated with dementia and plasma Alzheimer’ s biomarkers in older adults: The MIND‐China study

Abstract Background Cardiovascular risk factors and cardiovascular diseases (CVDs) have been linked with dementia. In addition, amyloid‐β (Aβ) is detected in the heart of patients with Alzheimer’s disease (AD). However, no population‐based studies have yet investigated the interrelationships of ventricular electrocardiographic (ECG) profiles (e.g., QT, JT, QRS intervals, and QRS axis angle) with dementia and plasma Alzheimer’s biomarkers. Method This population‐based cross‐sectional study included 5110 participants (age ≥65 years; 57.2% women) from the baseline assessments of the multimodal interventions to delay dementia and disability in rural China (MIND‐China) in March‐September 2018; of these, 1273 had data on plasma Aβ42, Aβ40, total‐tau, and neurofilament light chain (NfL) that were measured using the single molecule array (SIMOA) technology. Ventricular ECG parameters included QT, QTc, JT, JTc, QRS intervals, and QRS axis angle. The DSM‐IV criteria were followed for the diagnosis of dementia, the NIA‐AA criteria for AD, and NINDS‐AIREN criteria for vascular dementia (VaD). Data were analyzed using the general linear models, multinomial logistic models, and restricted cubic splines. Result Of the 5110 participants, 296 (5.79%) were diagnosed with dementia (192 with AD; 93 with VaD). The multivariable‐adjusted odds ratios (95% CI) of dementia associated with the quartiles of QT interval were 1.00 (reference), 1.66 (1.11‐2.50), 1.93 (1.25‐3.00), and 1.78 (1.10‐2.91), respectively. QTc, JT, and JTc intervals had analogous associations with dementia, and these ventricular ECG parameters were significantly associated with an increased likelihood of AD and VaD. The restricted cubic spline model suggested a significant association of QRS axis left deviation with VaD. In the plasma biomarker subsample, JT and JTc intervals were associated with multivariable‐adjusted β coefficients (95% CI) of ‐0.15 (‐0.27‐ ‐0.03) and ‐0.11 (‐0.20‐ ‐0.01), respectively, for Aβ42/Aβ40 ratio. The multivariable‐adjusted β coefficients (95% CI) of plasma NfL associated with QT, JT, and JTc intervals were 0.04 (0.01‐0.08), 0.06 (0.02‐0.09), and 0.04 (0.01‐0.07), respectively. Conclusion Ventricular ECG signatures for dementia and plasma Alzheimer’s biomarkers in rural‐dwelling older adults are characterized by altered ventricular repolarization and depolarization. These results support the view that Aβ metabolism and neurodegeneration might be involved in the associations of ventricular ECG profiles with dementia.