Lipids at the Nexus between Cerebrovascular Disease and Vascular Dementia: The Impact of HDL-Cholesterol and Ceramides

Cerebrovascular diseases and the subsequent brain hypoperfusion are at the basis of vascular dementia. Dyslipidemia, marked by an increase in circulating levels of triglycerides and LDL-cholesterol and a parallel decrease in HDL-cholesterol, in turn, is pivotal in promoting atherosclerosis which represents a common feature of cardiovascular and cerebrovascular diseases. In this regard, HDL-cholesterol has traditionally been considered as being protective from a cardiovascular and a cerebrovascular prospective. However, emerging evidence suggests that their quality and functionality play a more prominent role than their circulating levels in shaping cardiovascular health and possibly cognitive function. Furthermore, the quality of lipids embedded in circulating lipoproteins represents another key discriminant in modulating cardiovascular disease, with ceramides being proposed as a novel risk factor for atherosclerosis. This review highlights the role of HDL lipoprotein and ceramides in cerebrovascular diseases and the repercussion on vascular dementia. Additionally, the manuscript provides an up-to-date picture of the impact of saturated and omega-3 fatty acids on HDL circulating levels, functionality and ceramide metabolism.

Automated summary

Cerebrovascular diseases and brain hypoperfusion form the basis of vascular dementia. Dyslipidemia, characterized by an increase in triglycerides and LDL-cholesterol levels and a decrease in HDL-cholesterol, promotes atherosclerosis in cardiovascular and cerebrovascular diseases. The quality and functionality of HDL-cholesterol play a significant role in cardiovascular health and cognitive function, and ceramides embedded in lipoproteins are proposed as a novel risk factor for atherosclerosis. This review discusses the role of HDL lipoprotein and ceramides in cerebrovascular diseases and their impact on vascular dementia, as well as the influence of saturated and omega-3 fatty acids on HDL levels and ceramide metabolism.