World-First Study Identifies Brain Changes Caused by High Blood Pressure

A new study has, for the first time, identified specific brain areas damaged by high blood pressure.

The research, published in the European Heart Journal, suggests that this damage may contribute to mental decline and eventually dementia.

Powerful data source to understand high blood pressure

High blood pressure affects over one billion people globally and less than half of that population has been diagnosed and treated. It is well known that high blood pressure can affect brain function and produce long-lasting changes, but the exact mechanisms behind these changes have remained unclear.

The new study utilized a large data source of brain imaging data comprising 30,000 participants in the UK Biobank study, each of whom underwent magnetic resonance imaging (MRI) scans. This was paired with genetic information from the Biobank, Cognitive Genomics Consortium (COGENT) and the International Consortium for Blood Pressure. Together, these data were used to determine differences in cognitive function from the scans, and, using a technique called mendelian randomization, whether high blood pressure caused these alterations, or whether it was simply associated with them.

Professor Tomasz Guzik, chair of Cardiovascular Medicine at the University of Edinburgh, and the study’s senior author, said, “We have identified specific parts of the brain that are affected by increases in blood pressure, including areas called the putamen and specific white matter regions.”

In total, Guzik and colleagues identified nine areas of the brain that showed blood pressure-related alterations. Notable regions affected included:

• The putamen – a round structure in the base of the brain, responsible for regulating movement and influencing various types of learning
• The anterior thalamic radiation – a region of white matter that links different parts of the brain that is involved in executive function
• The anterior corona radiata and anterior limb of the internal capsule – white matter brain regions involved in decision-making and emotion management

The changes included lowered brain volume and surface area and modifications to connectivity and brain activity.

Co-author of the study, Professor Joanna Wardlaw, head of Neuroimaging Sciences at the University of Edinburgh, said: “It has been known for a long time that high blood pressure is a risk factor for cognitive decline, but how high blood pressure damages the brain was not clear. This study shows that specific brain regions are at particularly high risk of blood pressure damage, which may help to identify people at risk of cognitive decline in the earliest stages, and potentially to target therapies more effectively in future.”

Statistical innovation

The study produced no new data but was able to assess the causality of high blood pressure on brain changes by using a statistical technique called Mendelian randomization. “Mendelian randomization is a way of using genetic information to understand how one thing affects another,” said Guzik. “In particular, it tests if something is potentially causing a certain effect, or if the effect is just a coincidence. It works by using a person's genetic information to see if there is a relationship between genes predisposing to higher blood pressure and outcomes. If there is a relationship, then it is more likely that the high blood pressure is causing the outcome. This is because genes are randomly passed down from parents, so they are not influenced by other factors that could confuse the results. In our study, if a gene that causes high blood pressure is also linked to certain brain structures and their function, then it suggests that high blood pressure might really be causing brain dysfunction at that location.”

Limitations of the study are related to the Biobank’s cohort, which is primarily white and middle-aged. Further analysis will have to be conducted to enable the findings to be extrapolated to other groups.

Reference: Siedlinski M, Carnevale L, Xu X, et al. Genetic analyses identify brain structures related to cognitive impairment associated with elevated blood pressure. Eur. Heart J. 2023. doi: 10.1093/eurheartj/ehad101.

This article is a rework of a press release issued by the European Society of Cardiology. Material has been edited for length and content.