Hypertension affects the brain long before it’s detected

Most people hear the word hypertension and think about heart trouble. Doctors warn us about damaged arteries, strokes, and heart attacks.

What many people do not realize is that the brain starts feeling the strain long before anyone sees a rise in blood pressure on a clinic’s screen.

New research shows that tiny shifts inside the brain spark trouble early, and those changes may set the stage for memory loss years down the line.

Hypertension’s early brain damage

Scientists have suspected this for a long time because people with hypertension face a higher risk of cognitive disorders.

The link has been clear, but the reason behind it has not been. Many medications bring blood pressure down, yet patients still experience memory problems. That disconnect pushed researchers to look deeper.

After digging into the biology of the brain’s cells, a team at Weill Cornell Medicine found that hypertension causes damage in the brain well before blood pressure itself rises.

The investigators studied mice to track what happens inside individual cells during the early stages of hypertension.

Damage starts before symptoms

The scientists triggered hypertension in mice by giving them angiotensin, a hormone that raises blood pressure. They checked the animals’ brains three days later and again after 42 days. At the early point, blood pressure had not yet climbed, but the brain already showed trouble.

Endothelial cells, which line the blood vessels, acted older than they should. Their energy metabolism dropped, and they showed signs of senescence, meaning they had stopped dividing.

The researchers also found early hints that the blood-brain barrier was beginning to weaken. That barrier normally shields the brain from harmful substances.

Neuron damage drives decline

Interneurons were also affected. These cells help control communication between sensory and motor neurons. When they malfunction, the balance between inhibitory and excitatory signals shifts – an imbalance appears in Alzheimer’s disease.

Oligodendrocytes were the third group hit early. These cells make myelin, the protective coating around nerve fibers.

When the genes that maintain and replace myelin fail to activate properly, neurons lose their ability to communicate.

That loss eventually affects thinking and memory. Later, at day 42, even more gene expression changes showed up, and the mice displayed cognitive decline.

Brain changes appear quickly

Researchers found that the major cells responsible for cognitive impairment were affected just three days after inducing hypertension in mice before blood pressure increased.

“The bottom line is something beyond the dysregulation of blood pressure is involved,” said Dr. Anthony Pacholko, postdoctoral associate in neuroscience at Weill Cornell, who co-led the work. “The extent of the early alterations induced by hypertension was quite surprising.”

“Understanding how hypertension affects the brain at the cellular and molecular levels during the earliest stages of the disease may aid in developing therapeutic strategies to combat the progression of neurodegeneration in people with hypertension.”

Patients with hypertension have a 1.2- to 1.5-fold higher risk of developing cognitive disorders than people without the condition.

Medicines that reverse damage

The team also tested losartan, an anti-hypertension drug already in use. It blocks the angiotensin receptor.

“In some human studies, the data suggest that angiotensin receptor inhibitors may be more beneficial to cognitive health than other drugs that lower blood pressure,” said Dr. Costantino Ladecola, director of the Feil Family Brain and Mind Research Institute at Cornell University.

In the study, losartan reversed the early effects of hypertension on endothelial cells and interneurons in mice. That finding gives doctors a reason to think more carefully about which medications may offer brain benefits in addition to heart protection.

“Hypertension is a leading cause of damage to the heart and the kidneys, that can be prevented by antihypertensive drugs. So independent of cognitive function, treating high blood pressure is a priority, no matter what,” said Dr. Ladecola.

Mapping hypertension’s early effects

The team now aims to understand how early aging of small blood vessels triggers damage in interneurons and oligodendrocytes.

The scientists plan to keep untangling these links to figure out whether the brain can be protected before damage sets in.

Hypertension affects millions of people. Many live with it for years without symptoms, and the brain may be carrying the weight of it far earlier than anyone assumed. Research like this may help doctors one day stop cognitive decline before it starts.

The full study was published in the journal Neuron.

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