Abstract
Background: P-wave terminal force in lead V1 (PTFV1) on electrocardiography has been associated with atrial fibrillation and ischemic stroke. Objective: To investigate whether PTFV1 is associated with cerebral small vessel disease (CSVD) markers and etiological subtypes of cognitive impairment and dementia. Methods: Participants were recruited from ongoing memory clinic study between August 2010 to January 2019. All participants underwent physical and medical evaluation along with an electrocardiography and 3 T brain magnetic resonance imaging. Participants were classified as no cognitive impairment, cognitive impairment no dementia, vascular cognitive impairment no dementia, and dementia subtypes (Alzheimer's disease and vascular dementia). Elevated PTFV1 was defined as > 4,000μV×ms and measured manually on ECG. Results: Of 408 participants, 78 (19.1%) had elevated PTFV1 (37 women [47%]; mean [SD] age, 73.8 [7.2] years). The participants with elevated PTFV1 had higher burden of lacunes, cerebral microbleeds (CMB), and cortical microinfarcts. As for the CMB location, persons with strictly deep CMB and mixed CMB had significantly higher PTFV1 than those with no CMB (p = 0.005, p = 0.007). Regardless of adjustment for cardiovascular risk factors and/or heart diseases, elevated PTFV1 was significantly associated with presence of CMB (odds ratio, 2.26; 95% CI,1.33-3.91). Conclusion: Elevated PTFV1 was associated with CSVD, especially deep CMB. PTFV1 in vascular dementia was also higher compared to Alzheimer's disease. Thus, PTFV1 might be a potential surrogate marker of brain-heart connection and vascular brain damage.
| Original language | English |
|---|---|
| Pages (from-to) | 1093-1105 |
| Number of pages | 13 |
| Journal | Journal of Alzheimer's Disease |
| Volume | 86 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 5 Apr 2022 |
Bibliographical note
Funding Information:There are several limitations in this study. Firstly, Due to the retrospective design, we could not obtain ECG data from all the participants and ECG and MRI were not conducted at the same time, since both PTFV1 and CSVD burden might change over the period. However, as shown in Supplementary Table 1, the excluded participants did not have different characteristics from the final participants except for history of coronary artery disease. And adjusting the interval between ECG and MRI did not affect the significant association with CMB and the other CSVD markers. Secondly, we cannot exclude the possibility of misclassification or measurement error for the calculation of PTFV1. However, manual measurement is common and showed excellent inter-and intra-rater reliability. Thirdly, this study might have limited generalizability because it was conducted in a memory clinic cohort in Asia. Around 85% of the subjects were Chinese. According to our previous studies, Asians have a higher burden of vascular risk factors such as hypertension, hyperlipidemia, and diabetes and higher prevalence and incidence of cerebrovascular disease compared to Caucasians [2, 31]. Moreover, a recent meta-analysis showed that elevated PTFV1 had lower risk of atrial fibrillation occurrence in Europe (odds ratio = 1.05) compared with Asia (odds ratio = 1.89) and United States (odds ratio = 1.43) [45]. To validate the associations between PTFV1 and CSVD, further studies are warranted. Finally, the strength of this study is that; study participants were recruited from memory clinic with different risk factor profiles that enable to analyze the association of PTFV1 with a diverse group of patients. We used 3 T MRI scan to grade markers of CSVD and included more novel markers such as CMIs. Furthermore, this is one of the few studies that explores the associations of elevated PTFV1 We acknowledge all the Memory Aging and Cognition Centre, National University Hospital coordinators and phycologists for their contribution to recruitment and data acquisition. This study was supported by the National Medical Research Council grants; NMRC/CG/NUHS/2010 - R184-005-184-511, NMRC/CG/013/2013, NMRC/CIRG/ 1446/2016, National University Health System Center grant SEED funding (R-608-000-275-511), National University of Singapore start-up grant (R-608-000-257-133).
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