Age-related cognitive impairment and dementia are an increasing societal burden. Epidemiological studies indicate that lifestyle factors, e.g. physical, cognitive and social activities, correlate with reduced dementia risk; moreover, positive effects on cognition of physical/cognitive training have been found in cognitively unimpaired elders. Less is known about effectiveness and action mechanisms of physical/cognitive training in elders already suffering from Mild Cognitive Impairment (MCI), a population at high risk for dementia. We assessed in 113 MCI subjects aged 65–89 years, the efficacy of combined physical-cognitive training on cognitive decline, Gray Matter (GM) volume loss and Cerebral Blood Flow (CBF) in hippocampus and parahippocampal areas, and on brain-blood-oxygenation-level-dependent (BOLD) activity elicited by a cognitive task, measured by ADAS-Cog scale, Magnetic Resonance Imaging (MRI), Arterial Spin Labeling (ASL) and fMRI, respectively, before and after 7 months of training vs. usual life. Cognitive status significantly decreased in MCI-no training and significantly increased in MCI-training subjects; training increased parahippocampal CBF, but no effect on GM volume loss was evident; BOLD activity increase, indicative of neural efficiency decline, was found only in MCI-no training subjects. These results show that a non pharmacological, multicomponent intervention improves cognitive status and indicators of brain health in MCI subjects.

Aims/hypothesis Endothelium-derived factors are thought to be physiological modulators of large artery stiffness. The aim of the study was to investigate whether endothelial function could be a determinant of arterial stiffness in essential hypertensive patients, in relation with the concomitant presence of type 2 diabetes mellitus. Methods The study included 341 participants (84 hypertensive patients with and 175 without type 2 diabetes mellitus, 82 matched controls). Brachial artery endotheliumdependent flow-mediated dilation (FMD) was determined by high-resolution ultrasound and computerised edge detection system. Applanation tonometry was used to measure carotid-femoral pulse wave velocity (PWV). Results Hypertensive patients with diabetes had higher PWV (10.1±2.3 m/s vs 8.6±1.4 m/s, p<0.001) and lower FMD (3.51±2.07 vs 5.16±2.96%, p<0.001) than non-diabetic hypertensive patients, who showed impaired vascular function when compared with healthy participants (7.9±1.6 m/s and 6.68 ± 3.67%). FMD was significantly and negatively correlated to PWV only in hypertensive diabetic patients (r0−0.456, p<0.001), but not in hypertensive normoglycaemic patients (r0−0.088, p00.248) or in healthy participants (r 00.008, p 00.946). Multivariate analysis demonstrated that, in the diabetic group, FMD remained an independent predictor of PWV after adjustment for confounders (r 2 00.083, p 00.003). Subgroup analysis performed in non-diabetic hypertensive patients revealed that neither obesity nor the metabolic syndrome affected the relationship between FMD and PWV. Conclusions/interpretation Endothelial dysfunction is a determinant of aortic stiffness in hypertensive diabetic patients but not in hypertensive patients without diabetes. These results suggest that type 2 diabetes mellitus on top of hypertension might worsen arterial compliance by endothelium-related mechanisms.

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Central blood pressure is dependent on the stiffness of large arteries and pulse wave reflection. These parameters are very important in the development of hypertensive target organ disease. Moreover, recent clinical studies have shown their independent predictive value for cardiovascular morbidity and mortality. Therefore, 2007 guidelines for the management of hypertension inserted the evaluation of central arterial stiffness as an important component for assessing total cardiovascular risk. Differences in the way various antihypertensive drugs affect arterial stiffness and central hemodynamics may explain the greater cardio-vascular protection provided by newer drugs (eg, renin-angiotensin system blockers or calcium channel blockers) independent of peripheral blood pressure reduction, as shown by recent clinical studies. However, the predictive value of the attenuation of arterial stiffness, wave reflections, and central blood pressure still needs to be confirmed in prospective, long-term, large-scale therapeutic trials. Thus, whether these measurements should be routinely performed as a diagnostic or therapeutic indicator remains debatable.