## 4 Discussion
### Alzheimer's Disease and Cardiovascular Risk Factors
#### 4.2.3 Cardiac Pathology and Alzheimer's Disease  
We have reported that a significant association between cardiac pathology (according to the ICD, 11 th revision of the major groups of circulatory system diseases of the WHO [23]) and AD was observed, manifested by a higher percentage of individuals with cardiac pathology in the group diagnosed with AD (29.42%) compared to the CG (8.87%). Our results could suggest a connection between heart disease and AD [62]. Two studies [63; 64] have shown that heart failure, in addition to coronary heart disease, may contribute to an increased risk of AD. Mechanisms such as impaired cerebral blood flow, systemic inflammation and amyloid-\(\beta\) accumulation in the brain support this link [63; 64]. Additionally, studies have explored the relationship between cardiac functional parameters and AD. In a recent study by [PERSON] et al. [65], the left ventricular ejection fraction (LVEF), a key indicator of cardiac dysfunction, was associated with cerebrospinal fluid (CSF) biomarkers of AD in cognitively normal individuals. Participants with lower LVEF had significantly higher levels of CSF total \(\tau\) and an increased \(\tau/\Delta\beta 42\) ratio, suggesting a link between cardiac function and AD pathology. These associations were particularly evident in women and individuals younger than 65 years old, reinforcing the hypothesis that maintaining cardiac function may be relevant for AD prevention. Furthermore, an experimental study by [PERSON] et al. [66] using the 5 XFAD mouse model of AD demonstrated that these mice exhibited a significant reduction in cardiac fractional shortening and ejection fraction compared to wild-type controls. Additionally, 5 XFAD mice showed alteredelectrical activity, decreased calcium influx in cardiomyocytesocytes, and increased activation of AMP-activated protein kinase (AMPK), indicative of energy metabolism dysfunction. [PERSON] et al. [67] have investigated various cardiac diseases associated with cognitive impairment. In that study, they conducted a meta-analysis assessing the association of coronary heart disease and cognitive impairment. Their results [67] showed a positive association with an RR of 1.27 between coronary heart disease and the risk of cognitive impairment, as well as an association with an RR of 1.49 between myocardial infarction and the risk of cognitive impairment. However, between angina pectoris and the risk of cognitive impairment, there was no significant association (RR: 0.99). Nevertheless, these authors showed that individuals with coronary heart disease have an increased risk of vascular dementia, but not of AD [67]. Consistently, [PERSON] et al. [68] examined the relationship of heart disease, including atrial fibrillation, coronary artery disease, heart failure and carotid occlusive disease, with brain A\(\beta\) burden. Their findings, through a meta-analysis study, revealed the absence of significant differences in amyloid burden between the affected individuals and the CG. This evidence suggests that, as yet, there are no current studies to support such a relationship [68]. However, [PERSON] et al. [69] included 43 studies in their meta-analysis, in which they aimed to study the association between atrial fibrillation and cognitive impairment in various dementias. Among their results, they showed that atrial fibrillation was significantly associated with an increased risk of vascular dementia (OR: 1.7) and Alzheimer's dementia (OR: 1.4). These researchers [69] concluded that atrial fibrillation increases the risk of cognitive impairment, vascular dementia and AD. Also, a recent case-control study [70] investigated core blood biomarkers of AD, specifically, \(\tau\) protein and A\(\beta\)-peptide, in individuals with severe brain injury following cardiac arrest. The study reported elevated levels of A\(\beta\)-peptide 40 and A\(\beta\)-peptide 42 in the blood 48-72 h post-arrest.