Scientists at Weill Cornell Medicine have made an important discovery about high blood pressure, also known as hypertension.
Their research shows that hypertension may begin harming the brain long before blood pressure readings actually rise. This means damage may already be happening inside the brain even when a person’s blood pressure still looks normal on a medical chart.
These findings help explain why people with hypertension have a much higher risk of memory problems, vascular cognitive impairment, and Alzheimer’s disease.
Hypertension is extremely common, especially as people get older. Doctors already know it is one of the strongest risk factors for cognitive decline. People with high blood pressure have about a 1.2 to 1.5 times higher chance of developing memory problems compared to those with normal blood pressure.
What scientists have long struggled to understand is why medicines that lower blood pressure do not always prevent the brain from getting worse. This new study uncovers part of the answer.
The research team used mice to study the early stages of hypertension. They raised the mice’s blood pressure by giving them a hormone called angiotensin, which works in a similar way to how hypertension develops in humans.
Then they tested what was happening inside the brain only three days later. At this early point, the mice had not yet developed high blood pressure—but their brain cells were already changing in harmful ways.
The scientists found that three major types of brain cells were affected very quickly: endothelial cells, interneurons, and oligodendrocytes. Endothelial cells line the inside of blood vessels and help them stay healthy. In the mice, these cells looked older than they should have and had lower energy.
They also showed signs of early damage to the blood-brain barrier. This barrier is like a filter that protects the brain by letting good nutrients in and keeping harmful substances out. When it weakens, toxins or unwanted molecules can slip into the brain and cause long-term damage.
Interneurons were also affected early. These cells help keep a healthy balance between nerve signals that excite the brain and signals that calm it down. When interneurons become damaged, that balance breaks down. A similar imbalance is seen in Alzheimer’s disease, which may help explain why hypertension increases the risk of dementia.
The third cell type, oligodendrocytes, was also harmed. These cells make myelin, a protective coating around nerve fibers that helps brain cells communicate quickly and clearly. When oligodendrocytes cannot maintain or replace myelin, communication slows down and thinking becomes harder. Over time, this can lead to cognitive decline.
When the researchers looked again after 42 days, the mice now had clear high blood pressure—and their cognitive abilities had worsened.
The early signs seen on day three had progressed into more serious and widespread changes in gene expression across brain cells. This suggests that hypertension starts harming the brain long before the condition becomes measurable in regular blood pressure tests.
One hopeful part of the study involved a medication called losartan. This drug is already widely used to treat hypertension by blocking the angiotensin receptor.
When the researchers gave losartan to the mice, it reversed many of the early harmful effects on endothelial cells and interneurons. This finding may help explain why some blood pressure medications appear to protect brain health better than others.
These discoveries strongly suggest that the damage from hypertension is not caused only by high blood pressure itself. Instead, the harmful process begins earlier, driven by molecular and cellular changes in blood vessels and brain cells. This process makes blood vessels age faster and weakens their ability to support the brain.
In reviewing and analyzing these findings, it becomes clear that hypertension is more than a simple increase in blood pressure. It is a progressive disease that silently rewires the brain. The study reveals that brain cells begin changing after only a few days of exposure to hypertension-related hormones, long before any symptoms appear.
This suggests that focusing solely on lowering blood pressure may not be enough to protect the brain. Medications that target the angiotensin system, such as losartan, may offer additional benefits by blocking the early molecular signals that damage blood vessels and nerve cells.
The research also shows why early detection and early treatment of hypertension are essential. By the time blood pressure rises and becomes measurable, harmful changes may already be well under way.
More studies are needed to understand exactly how blood vessel aging triggers damage in neurons and oligodendrocytes, but the current results point toward new ways to prevent dementia and cognitive decline.
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The study is published in Neuron.
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