Cognitive Impairment in Frail Hypertensive Elderly Patients: Role of Hyperglycemia

Abstract

Endothelial dysfunction is a key hallmark of hypertension, which is a leading risk factor for cognitive decline in older adults with or without frailty. Similarly, hyperglycemia is known to impair endothelial function and is a predictor of severe cardiovascular outcomes, independent of the presence of diabetes. On these grounds, we designed a study to assess the effects of high-glucose and metformin on brain microvascular endothelial cells (ECs) and on cognitive impairment in frail hypertensive patients. We tested the effects of metformin on high-glucose-induced cell death, cell permeability, and generation of reactive oxygen species in vitro, in human brain microvascular ECs. To investigate the consequences of hyperglycemia and metformin in the clinical scenario, we recruited frail hypertensive patients and we evaluated their Montreal Cognitive Assessment (MoCA) scores, comparing them according to the glycemic status (normoglycemic vs. hyperglycemic) and the use of metformin. We enrolled 376 patients, of which 209 successfully completed the study. We observed a significant correlation between MoCA score and glycemia. We found that hyperglycemic patients treated with metformin had a significantly better MoCA score than hyperglycemic patients treated with insulin (18.32 ± 3.9 vs. 14.94 ± 3.8; p < 0.001). Our in vitro assays confirmed the beneficial effects of metformin on human brain microvascular ECs. To our knowledge, this is the first study correlating MoCA score and glycemia in frail and hypertensive older adults, showing that hyperglycemia aggravates cognitive impairment.

Left Atrial Strain as a Predictor of Left Ventricular Diastolic Dysfunction in Patients with Arterial Hypertension

“…Noncardiac comorbidities are highly prevalent in HFPEF [15] with hypertension being the most prevalent of all [16]. Hypertension leads to chronic endothelial dysfunction, promoting oxidative stress, inflammation, and atherosclerosis [17,18]. Hyperglycemia's role in endothelial function impairment is well known together with being a risk factor for severe cardiovascular outcomes, independent of the presence of diabetes [17].…”

The Temporal Pattern of Arterial Stiffness during Aging: A Large-Scale Cross-Sectional Study

“…In addition, pulse wave velocity was found to be associated with other diseases such as frailty. Frailty is a complex physiological state characterized by significant physical and cognitive impairment [ 11 ]. A meta-analysis has recently shown a strong correlation between pulse-wave velocity and frailty.…”

“…A healthy baPWV index for individuals of all ages is approximately 1800 cm/s, and an index value greater than this benchmark is associated with an increasingly higher risk of developing cardiovascular disease [ 16 ]. Many underlying physiological conditions such as hyperlipidemia, hypertension, diabetes, and hyperglycemia have previously been shown to elevate baPWV and contribute to the decline of arterial function [ 11 – 13 , 17 – 20 ]. Additionally, age and sex have been shown to influence the stiffness of arteries as well as the risk of developing cardiovascular disease [ 17 ].…”

Serum Inflammatory Factors and Oxidative Stress Factors Are Associated With Increased Risk of Frailty and Cognitive Frailty in Patients With Cerebral Small Vessel Disease

“…We know that the causes of frailty and cognitive frailty are very complex (46,47). Taken together, they involve the interaction of genetic, physiological, psychological, social, and environmental factors (48). A number of studies have shown the relationship between inflammation, oxidative stress, frailty, and cognitive frailty (49)(50)(51).…”