Ventricular Electrocardiographic Signatures Associated with Dementia and Plasma Alzheimer’s Disease Biomarkers in Older Adults: A Population-Based Study

Abstract

Background: Evidence has emerged that altered ventricular electrocardiogram profiles are associated with dementia, but the neuropathological mechanisms underlying their associations are poorly understood. Objective: To investigate the interrelationships of ventricular electrocardiogram profiles with dementia and plasma Alzheimer’s disease (AD) biomarkers among older adults. Methods: This population-based cross-sectional study included 5,153 participants (age ≥65 years; 57.3% women) living in rural communities in China; of these, 1,281 had data on plasma amyloid-β (Aβ)40, Aβ 42, total-tau, and neurofilament light chain (NfL) protein. The QT, QTc, JT, JTc, QRS intervals, and QRS axis were derived from the 10-second electrocardiogram recording. The DSM-IV criteria were followed for clinical diagnosis of dementia, the NIA-AA criteria for AD, and the NINDS-AIREN criteria for vascular dementia (VaD). Data were analyzed using general linear models, multinomial logistic models, and restricted cubic splines. Results: Of the 5,153 participants, 299 (5.8%) were diagnosed with dementia, including 194 with AD and 94 with VaD. Prolonged QT, QTc, JT, and JTc intervals were significantly associated with all-cause dementia, AD, and VaD (p < 0.05). Left QRS axis deviation was significantly associated with all-cause dementia and VaD (p < 0.01). In the subsample of plasma biomarkers (n = 1,281), prolonged QT, JT, and JTc intervals were significantly associated with a lower Aβ 42/Aβ 40 ratio and higher plasma NfL concentrations (p < 0.05). Conclusion: Alterations in ventricular repolarization and depolarization are independently associated with all-cause dementia, AD, VaD, and AD plasma biomarkers in older adults (age ≥65 years). Ventricular electrocardiogram parameters may be valuable clinical markers for dementia and the underlying AD pathologies and neurodegeneration.

Relationship between Alzheimer dementia and QT interval: A meta‐analysis

“…One of these studies evaluated the relationship in a multivariate analysis adjusting for age, gender, education, smoking, alcohol intake, BMI, APOE genotype, resting heart rate, the number of chronic diseases, and use of anti-thrombotic agents, cardiac agents, and QT prolonging drugs. 33 In that multivariable analysis, QT was associated with dementia. 33 Three studies examine QTc and the degree of cognitive impairment as assessed by MMSE.…”

“…33 In that multivariable analysis, QT was associated with dementia. 33 Three studies examine QTc and the degree of cognitive impairment as assessed by MMSE. Danese et al reported a significant correlation between QTc and both raw MMSE data as well as MMSE adjusted for age and gender.…”

“…22 Mao et al reported on a crosssectional population study in which 5.2% had dementia of which 194 had AD, 94 had vascular dementia, and 11 had other kinds of dementia. 33 Dementia was defined according to standardized references. MCI was defined somewhat differently in one of the three studies.…”

“…In the other study, the QT interval was assessed by the ECG computer algorithm and details were not specified. 33 In each study, the QT interval was adjusted for heart rate by the Bazett formula, 34 hereafter referred to by its abbreviation QTcBZT. 35 There was an overall significant difference in QTc between patients with dementia and those with MCI after pooling the three studies (Figure 2).…”

“…6 The data for their entire study population were not available. Recognizing this limitation, their MCI group 6 and the entire study population from Danese et al 22 and Mao et al 33 were assessed (Figure 4). There was a significant (P < 0.001) correlation between MMSE and QTc.…”