A new study from Weill Cornell Medicine reveals that hypertension begins harming the brain early, disrupting blood vessels, neurons, and white matter before blood pressure increases. These changes, observed in mice, may explain the link between hypertension and cognitive disorders like Alzheimer's. The research, published on November 14 in Neuron, suggests potential benefits from medications like losartan.
Investigators at Weill Cornell Medicine conducted a preclinical study modeling hypertension in mice using the hormone angiotensin, which mimics human blood pressure elevation. They examined brain cell responses at three days—before blood pressure rose—and at 42 days, when pressure was high and cognitive issues appeared.
At the three-day mark, gene expression shifted in endothelial cells lining blood vessels, showing accelerated aging with reduced energy metabolism and increased senescence markers. The blood-brain barrier weakened early, allowing potential entry of harmful substances. Interneurons, which balance nerve signals, suffered damage resembling early Alzheimer's patterns. Oligodendrocytes, responsible for myelin insulation on nerve fibers, expressed fewer genes for myelin maintenance and regeneration, impairing neuron communication.
By day 42, more changes emerged, aligning with cognitive decline. "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. Co-lead author Dr. Anthony Pacholko, a postdoctoral associate in neuroscience, noted, "The extent of the early alterations induced by hypertension was quite surprising."
The study highlights that people with hypertension face a 1.2 to 1.5-fold higher risk of cognitive problems, yet common medications often fail to protect cognition despite controlling pressure. Encouragingly, losartan, an angiotensin receptor inhibitor, reversed damage in endothelial cells and interneurons. "In some human studies, the data suggest that the angiotensin receptor inhibitors may be more beneficial to cognitive health than other drugs that lower blood pressure," Dr. Iadecola added.
Researchers now aim to explore how vascular aging affects other brain cells and develop strategies to prevent cognitive consequences from hypertension.