Uncovering the Link Between Blood Pressure and Cognitive Decline

For the first time, researchers have discovered particular brain regions that are harmed by high blood pressure and may contribute to cognitive decline and dementia development.

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The Hidden Damage: High Blood Pressure's Impact on Brain Regions

High blood pressure is recognized to play a role in dementia and brain function loss. The study examined the effect of high blood pressure on cognitive function using a combination of magnetic resonance imaging (MRI) of brains, genetic analyses, and observational data from thousands of patients. The findings were then validated in a separate, large cohort of patients in Italy.

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Mapping the Mind: Identifying Specific Areas Impacted by High Blood Pressure

"By using this combination of imaging, genetic, and observational approaches, 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," said Tomasz Guzik, Professor of Cardiovascular Medicine at the University of Edinburgh (UK) and Jagiellonian University Medical College, Krakow (Poland), who led the research. We suspected that elevated blood pressure was affecting cognitive performance in several areas, such as memory loss, thinking skills, and dementia. When we tested our findings on a sample of high-blood-pressure patients in Italy, we discovered that the areas of the brain we had identified were damaged. “We hope that our findings may help us to develop new ways to treat cognitive impairment in people with high blood pressure. Studying the genes and proteins in these brain structures could help us understand how high blood pressure affects the brain and causes cognitive problems. Moreover, by looking at these specific regions of the brain, we may be able to predict who will develop memory loss and dementia faster in the context of high blood pressure. This could help with precision medicine so that we can target more intensive therapies to prevent the development of cognitive impairment in patients most at risk.”

High blood pressure is prevalent, affecting 30% of people worldwide, with an additional 30% experiencing the early stages of the disease. According to research, it affects how well the brain functions and can produce long-term alterations. Yet, it was previously unknown how high blood pressure harms the brain and which specific areas are impacted.

Prof. Guzik and an international team of researchers used brain MRI imaging data from over 30,000 participants in the UK Biobank study, genetic information from genome-wide association studies (GWAS) from UK Biobank and two other international groups (COGENT and the International Consortium for Blood Pressure), and a technique called Mendelian randomize in research co-funded by the European Research Council, the British Heart Foundation, and the Italian Ministry of Health.

“Mendelian randomisation is a way of using genetic information to understand how one thing affects another,” said Prof. 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 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 be causing brain dysfunction at that location, leading to problems with memory, thinking and dementia.”

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High Blood Pressure's Impact on Specific Brain Regions Linked to Cognitive Decline

The researchers identified changes in nine areas of the brain that were connected to increased blood pressure and lower cognitive function. The putamen is a circular structure in the base of the frontal lobe of the brain that regulates movement and influences several types of learning. The anterior thalamic radiation, anterior corona radiata, and anterior limb of the internal capsule were all impacted, which are white matter tracts that connect and allow signaling between different portions of the brain. The anterior thalamic radiation is responsible for executive activities such as planning basic and complex everyday chores, whilst the other two regions are responsible for decision-making and emotion control.

These modifications included decreases in brain volume and cortex surface area, changes in connections between different sections of the brain, and changes in measurements of brain activity.

The first author of the study, Associate Professor Mateusz Siedlinski, also a researcher at the Jagiellonian University Medical College, said: “Our study has, for the first time, identified specific places in the brain that are potentially causally associated with high blood pressure and cognitive impairment. This was uniquely possible thanks to the availability of data from UK Biobank, including MRI brain images, and thanks to previous research identifying genetic variants that affect the structure and function of over 3000 areas of the brain.”

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.”

The study's limitations include the fact that participants in the UK Biobank project are mostly white and middle-aged, making it difficult to apply the findings to older persons.

Dr. Ernesto Schiffrin of Sir Mortimer B. Davis-Jewish General Hospital and McGill University in Montreal, Canada, and Dr. James Engert of the McGill University Health Centre Research Center in Montreal wrote the accompanying editorial. "Further mechanistic studies of the effects of BP (blood pressure) on cognitive function are required to uncover precise causal pathways and important brain areas," they write.

They highlight one of the study’s findings about systolic and diastolic blood pressure (SBP and DBP). “Perhaps one of the more interesting results in this study is the possible distinct causal effects of SBP vs. DBP. The authors observed some overlapping results for SBP and DBP on cognitive function when analysed in isolation. However, when each parameter is analysed after adjusting for the other, or in multivariable models, intriguing findings begin to emerge. DBP alone does not predict a decline in cognitive function, but in fact, is protective when adjusted for SBP. This result was true both observationally and when using Mendelian randomization.” They go on to discuss the possible reasons for this.

Source-Medindia