RESUMEN
Background: Comorbidity is a common problem among elderly people, significantly damaging individuals' health and healthcare systems. However, observational studies may be susceptible to residual confounding factors and bias. The present study aimed to assess the causal effect of common chronic disease comorbidity using the Mendelian randomization (MR) approach. Methods: Data for the present study were obtained from a community survey conducted between 2018 and 2020 in four counties in Ganzhou City, southern China. A cross-sectional survey was conducted using a multi-stage stratified random sampling method. A total of 1756 valid questionnaires were collected to analyze common chronic disease comorbidities. Genetic variants associated with hypertension, diabetes, stroke, and hyperlipidemia-related factors were selected as instrumental variables for univariate and multivariate MR analyses. Results: The self-reported prevalence of chronic disease in the older adult population in Southern China was 68.1%, with hypertension (46.1%), diabetes (10.5%), and hyperlipidemia (8.5%) being the three most common conditions. The prevalence of chronic disease comorbidity was 20.7% among the 12 chronic diseases studied. Hypertension was identified as a predictor of diabetes (OR [95% CI]: 1.114 [1.049, 1.184], p < 0.001), and diabetes mellitus was equally identified as a risk factor for hypertension (OR [95% CI]: 1.118 [1.069, 1.187], p < 0.001). Furthermore, high triglyceride levels were identified as a risk factor for hypertension (OR [95% CI]: 1.262 [1.129, 1.411], p < 0.001). In contrast to intracranial hemorrhages, hypertension had a significant impact on ischemic stroke (OR [95% CI]: 1.299 [1.161, 1.454], p < 0.001). Conclusion: The causal association between multiple cardiovascular and metabolism-related diseases is mediated by hypertension, with a bidirectional cause-and-effect relationship between hypertension and diabetes. Hypertension is a risk factor for ischemic stroke, and the hyperlipidemia-related factor triglycerides (TG) influence hypertension. Therefore, prioritizing hypertension prevention and control in the elderly is critical for effective chronic disease management.
RESUMEN
Lead is widely distributed in the environment and has become a global public health issue. It is well known that lead exposure induces not only neurodevelopmental toxicity but also neurodegenerative diseases, with learning and memory impairment in the later stage. However, the molecular mechanisms remain elusive. The present study investigated the effects of early life and lifetime lead exposure on cognition and identified the molecular mechanisms involved in aged rats. The results herein demonstrated that the lead concentration in peripheral blood and brain tissues in aged rats was significantly increased in a lead dose-dependent manner. High-dose lead exposure caused cognitive functional impairment in aged rats, concomitant with a longer escape latency and a lower frequency of crossing the platform via Morris water maze testing compared to those in the control and low-dose lead exposure groups. Importantly, neuron functional defects were still observed even in early life lead exposure during the prenatal and weaning periods in aged rats. The neurotoxicity induced by lead exposure was morphologically evidenced by a recessed nuclear membrane, a swollen endoplasmic reticulum, and mitochondria in the neurons. Mechanistically, the exposure of aged rats to lead resulted in increasing free calcium concentration, reactive oxygen species, and apoptosis in the hippocampal neurons. Lead exposure increased RyR3 expression and decreased the levels of p-CaMKIIα/CaMKIIα and p-CREB/CREB in the hippocampus of aged rats. These findings indicated that early life lead exposure-induced cognition disorder was irreversible in aged rats. Lead-induced neurotoxicity might be related to the upregulation of RyR3 expression and high levels of intracellular free calcium with increasing lead concentration in injured neurons.