Hypertension May Harm The Brain Far Earlier Than Previously Believed, Study Finds

Managing hypertension remains essential for preventing well-known damage to the heart and kidneys. Now a new study has said hypertension begins damaging critical brain cells and blood vessels too well before any measurable rise in blood pressure is detected.

The findings by researchers at Weill Cornell Medicine and published in Neuron, shed fresh light on why high blood pressure is a major driver of cognitive decline, including vascular cognitive impairment and Alzheimer’s disease.

The study suggests that hypertension triggers early molecular changes in the brain—long before symptoms appear—that may one day be targeted to prevent dementia.

Researchers noted that people with hypertension face a 1.2 to 1.5 times higher risk of developing cognitive disorders, but the mechanisms behind this link have remained unclear. While current antihypertensive drugs often succeed in lowering blood pressure, they have shown limited benefit for brain health—indicating that the brain may suffer damage through pathways independent of blood pressure itself.

“We found that the major cells responsible for cognitive impairment were affected just three days after inducing hypertension in mice—before blood pressure increased,” said senior author Dr. Costantino Iadecola, director of the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine. “The bottom line is something beyond the dysregulation of blood pressure is involved.”

The research team, co-led by Dr. Anthony Pacholko, used angiotensin—a hormone known to raise blood pressure—to induce hypertension in mice. They then analysed the molecular changes occurring in different brain cell types at two points: three days after induction, when blood pressure was still normal, and 42 days later, when both hypertension and cognitive deficits had fully developed.

At the three-day mark, dramatic gene-expression changes emerged in endothelial cells, interneurons and oligodendrocytes. Endothelial cells, which line blood vessels, showed signs of premature ageing, reduced energy metabolism and early weakening of the blood–brain barrier. Interneurons, which maintain the balance between excitatory and inhibitory signals in the brain, exhibited damage similar to that seen in Alzheimer’s disease.

Oligodendrocytes—responsible for forming and maintaining the myelin sheath around neurons—also failed to express key genes required for healthy white-matter function.

By day 42, these disruptions had intensified and were accompanied by measurable cognitive impairment in the mice.

“The extent of the early alterations induced by hypertension was quite surprising,” Dr. Pacholko said. “Understanding how hypertension affects the brain at the cellular and molecular levels during the earliest stages of the disease may provide clues to ways that can potentially block neurodegeneration.”

The study also found that losartan, a commonly prescribed angiotensin-receptor blocker, reversed several of the early cellular changes in the mouse model. Some human studies have hinted that this class of drugs may offer greater cognitive protection than other blood-pressure medications, though further research is needed.

Dr. Iadecola emphasised that while protecting cognitive function is vital, managing hypertension remains essential for preventing well-known damage to the heart and kidneys.