Impact of serum leptin and adiponectin levels on brain infarcts in patients with mild cognitive impairment and Alzheimer's disease: a longitudinal analysis.

Introduction: The adipokines leptin and adiponectin have been associated with atherosclerosis and the risk of cerebral infarcts. Pre-clinical studies, however, suggest a protective role against ischemic brain damage. In this study we analyzed the relationship between serum leptin and adiponectin levels and the onset or progression of brain infarcts in subjects with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Methods: All data were extracted from the ADNI database. The final population included 566 subjects, with 58 healthy controls, 396 MCI and 112 AD. All patients with available serum leptin and adiponectin levels at baseline were selected. Demographics, neuropsychological test results, CSF biomarkers, regional brain metabolism with FDG-PET data and the number of brain infarcts on longitudinal MRI scans were extracted. Results: Leptin levels were significantly lower in patients with MCI than controls at baseline, while adiponectin levels were not different between the groups. Multivariate logistic regression analysis at baseline for the presence of brain infarcts showed a predictive value for leptin but not for adiponectin. Multivariate longitudinal analysis showed that age was the only significant predictor of brain infarcts development at 15-year follow-up, while serum leptin and adiponectin levels did not play a role in this population. Discussion: The evidence on the pathogenetic or protective role of adipokines on ischemic brain damage is mixed. In this MCI and AD population, serum leptin and adiponectin were not associated with the development of brain infarcts; therefore, these results do not support the use of adipokines as biomarkers of cerebrovascular pathology in this population.

Atrial Fibrillation and Dementia: Focus on Shared Pathophysiological Mechanisms and Therapeutic Implications.

OBJECTIVES: Atrial fibrillation (AF) and dementia are highly prevalent chronic and debilitating conditions, especially affecting the older population. This review focuses on possible common pathophysiological mechanisms that could explain the association between the 2 conditions. DESIGN: Narrative review. SETTING AND PARTICIPANTS: Evidence from epidemiologic, observational, and interventional studies evaluating prevalence and incidence of cognitive impairment in patients with AF. METHODS: Broad literature search between December 2022 and May 2023. Eligible categories for inclusion comprised interventional studies, observational studies, systematic reviews, and meta-analysis. RESULTS: Evidence from different cohorts has shown that AF increases the risk of dementia, although the association with dementia subtypes is not always unequivocal. According to recent evidence, common pathophysiological mechanisms include thromboembolism and hypercoagulable states, proinflammatory state, infection, cerebral hypoperfusion, and brain atrophy. Moreover, we reviewed the evidence on therapeutic measures to prevent dementia in patients with AF. CONCLUSIONS AND IMPLICATIONS: Screening for cognition in patients with AF is of paramount importance, given the shared risk factors and common pathophysiological mechanisms. More evidence is needed to clarify whether antiarrhythmic and anticoagulant therapy have an impact on cognitive outcomes in AF patients.

Intricate relationship between obstructive sleep apnea and dementia in older adults.

Numerous evidence reports direct correlation between cognitive impairment, Alzheimer's disease and sleep disorders, in particular obstructive sleep apnea. Both obstructive sleep apnea and Alzheimer's disease are highly prevalent conditions whose incidence increases with age. Several studies demonstrate how sleep-disordered breathing may lead to poor cognition, even though the underlying mechanisms of this association remain partially unclear. According to the most recent studies, obstructive sleep apnea may be considered a modifiable risk factor for cognitive dysfunction. In the present review, the authors aim to integrate recent research examining obstructive sleep apnea and Alzheimer's disease biomarkers, also focusing on the mechanisms that support this correlation, including but not limited to the role of hypoxia and cardiovascular risk. Moreover, the potential favourable effect of obstructive sleep apnea therapy on cognitive function is discussed, to evaluate the benefits deriving from appropriate treatment of sleep-disordered breathing on cognition.

The elderly at risk: aldosterone as modulator of the immune response to SARS-CoV-2 infection.

The elderly population is the most susceptible to SARS-CoV-2 infection and develops the worst clinical phenotype with severe pneumonia and cardiac complications. Older COVID-19 patients are also at higher risk of sudden death, mainly attributable to electrolyte disorders and to an uncontrolled inflammatory response. After the identification of ACE 2 as the receptor of SARS-CoV-2 in human cells, several research studies have focused on the role of the activation of Renin Angiotensin System in COVID-19 clinical course. In the present opinion paper, we discuss the role of hyperaldosteronism in the increasing risk of cardiac complications in COVID-19 older patients. In particular, we focus on the immunoregulatory activity of aldosterone, as the last mediator of the Renin Angiotensin System cascade, in activating the innate and adaptive immune response related to SARS-CoV-2 infection in the elderly. Aldosterone may stimulate dendritic cells and the recruitment of monocytes/macrophages in the endothelium of coronary vessels, favoring the production of pro-inflammatory mediators and T-cells response. Higher basal levels of aldosterone together with SARS-CoV-2-induced production may explain the unfavorable course of COVID-19 in the elderly.

Why Do We Not Assess Sympathetic Nervous System Activity in Heart Failure Management: Might GRK2 Serve as a New Biomarker?

Heart failure (HF) represents the end-stage condition of several structural and functional cardiovascular diseases, characterized by reduced myocardial pump function and increased pressure load. The dysregulation of neurohormonal systems, especially the hyperactivity of the cardiac adrenergic nervous system (ANS), constitutes a hallmark of HF and exerts a pivotal role in its progression. Indeed, it negatively affects patients' prognosis, being associated with high morbidity and mortality rates, with a tremendous burden on global healthcare systems. To date, all the techniques proposed to assess the cardiac sympathetic nervous system are burdened by intrinsic limits that hinder their implementation in clinical practice. Several biomarkers related to ANS activity, which may potentially support the clinical management of such a complex syndrome, are slow to be implemented in the routine practice for several limitations due to their assessment and clinical impact. Lymphocyte G-protein-coupled Receptor Kinase 2 (GRK2) levels reflect myocardial ß-adrenergic receptor function in HF and have been shown to add independent prognostic information related to ANS overdrive. In the present manuscript, we provide an overview of the techniques currently available to evaluate cardiac ANS in HF and future perspectives in this field of relevant scientific and clinical interest.

Antithrombotic therapy in patients undergoing transcatheter aortic valve replacement: the complexity of the elderly.

Along with epidemiologic transitions of the global population, the burden of aortic stenosis (AS) is rapidly increasing and transcatheter aortic valve replacement (TAVR) has quickly spread; indeed, it is nowadays also employed in treating patients with AS at intermediate operative risk. Nonetheless, the less invasive interventional strategy still carries relevant issues concerning post-procedural optimal antithrombotic strategy, given the current indications provided by guidelines are not completely supported by evidence-based data. Geriatric patients suffer from high bleeding and thromboembolic risks, whose balance is particularly subtle due to the presence of concomitant conditions, such as atrial fibrillation and chronic kidney disease, that make the post-TAVR antithrombotic management particularly insidious. This scenario is further complicated by the lack of specific evidence regarding the 'real-life' complex conditions typical of the geriatric syndromes, thus, the management of such a heterogeneous population, ranging from healthy ageing to frailty, is far from being defined. The aim of the present review is to summarize the critical points and the most updated evidence regarding the post-TAVR antithrombotic approach in the geriatric population, with a specific focus on the most frequent clinical settings.