No abstract

It is well known that hypertension is the main modifiable risk factor leading to cognitive impairment and various forms of dementia. Leveraging functional MRI it has been possible to characterize hypertensives brain functional connectivity, a main feature of cerebral activation and health measurable by resting-state functional MRI. This characterization let us analyze how pathological conditions influence the cognitive processes and the spontaneous organization of brain activity, and have shown that hypertensive patients even before showing signs of vascular dementia have alterations in cerebral connections compared to normotensive patients. Our current question is whether different classes of antihypertensives, differentiated in mechanism of action and potential to cross the blood brain barrier may have different impact on cerebral functional organization. 42 hypertensives with controlled hypertension (SBP< 140mmHg e DBP< 90mmHg) were subjected to resting-state functional MRI. Functional connectivity was elaborated by CONN, according to an analysis pipeline to build functional connectivity networks matrices calculating the cross-correlation of BOLD signal among different brain regions. The obtained network of connections has been analyzed by general linear model, to implement regression models that highlight the connections in the brains modulated by the specific classes of antihypertensives analyzed. The application of regression models with age, sex, BMI, alcohol, smoke, SBP and DBP levels, heart rate as covariates shown that treatment with diuretics modulate a large connectivity network among Salience Network, Default Mode Network and Language Network (Fig. A). Ace-inhibitors treatment is associated with a significant modulation of a connection between Default Mode Network and the FrontoParietal Network (Fig. B), while ARBs are associated to the modulation of connections between Cerebellar and Language Networks (Fig. C). Finally, beta-blockers are associated with connections centered in Dorsal Attention Network and projected to Language and FrontoParietal Networks (Fig. D). Globally, the most relevant functional modulation of the brain is imposed by the use of diuretics, with a possible explanation in the fact that lowering global volume of circulating blood may have a significant impact on cerebral circulation. By this analysis, we will be able to take into account the central and cognitive impact of different antihypertensive drugs on the choice of best personalized treatment of hypertension.

Treating hypertension by drugs targeting the RAAS either blocking the Angiotensin receptor (ARBs) or inhibiting the Angiotensin Converting Enzyme (ACEi) have beneficial effects on cardiovascular health, preventing MI, stroke and global CV mortality. It is worth noting that no study investigated whether the two strategies targeting the RAAS have different effects on brain injury in hypertensive patients. To this aim, we investigated the correlation among microstructural integrity by DTI-MRI and the use of either class of drug. We recruited 51 hypertensives on ACEi or ARBs treatment and subjected them to advanced neuroimaging. DTI measures were normalized and analyzed by general linear model with age, sex, BMI, alcohol, smoke, SBP and DBP levels, heart rate as confounders to highlight alterations correlated to either treatment. The analysis shows that ARBs and ACEi exhibit an opposite and significant correlation with the microstructural integrity of the anterior commissure and the temporal subsection of the cingulum, reflecting a preserved microstructure in patients treated with ARBs compared with ACEi. This difference is also shown in pairwise comparison on anterior commissure (Table 1). In conclusion, our data suggest that ARBs may preserve specific white matter tracts integrity, suggesting that in hypertensive patients with cognitive dysfunction the use of ARBs should be preferred to protect brain microstructural integrity.