Specific Brain Damage Links Hypertension to Cognitive Impairment

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Specific Brain Damage Links Hypertension to Cognitive Impairment

Researchers have identified specific regions of the brain that appear to be damaged by high blood pressure. The finding may explain the link between hypertension and cognitive impairment.

They used genetic information from genome-wide association studies (GWASs) and MRI scans of the brain to study the relationship between hypertension, changes in brain structures, and cognitive impairment. Using Mendelian randomization techniques, they identified nine brain structures related to cognitive impairment that are affected by blood pressure.

3D reconstruction shows how high systolic blood pressure has affected the main tracts of white matter in the brain. Red shows the areas most affected by high blood pressure. The yellow areas are also affected but to a lesser extent.

The study was published online in the European Heart Journal on March 27.

"We knew before that raised blood pressure was related to changes in the brain, but our research has narrowed down the changes to those that appear to be potentially causally related to cognitive impairment," senior author Tomasz Guzik, professor of cardiovascular medicine, at the University of Edinburgh, United Kingdom, and of the Jagiellonian University, Krakow, Poland, told theheart.org | Medscape Cardiology.

"Our study confirms a potentially causal relationship between raised blood pressure and cognitive impairment, emphasizing the importance of preventing and treating hypertension," Guzik noted.

"But it also identifies the brain culprits of this relationship," he added.

In the future, it may be possible to assess these nine brain structures in people with high blood pressure to identify those at increased risk of developing cognitive impairment, he said. "These patients may need more intensive care for their blood pressure. We can also investigate these brain structures for potential signaling pathways and molecular changes to see if we can find new targets for treatment to prevent cognitive impairment."

For this report, the investigators married together different research datasets to identify brain structures potentially responsible for the effects of blood pressure on cognitive function, using results from previous GWASs and observational data from 39,000 people in the UK Biobank registry for whom brain MRI data were available.

 

First, they mapped brain structures potentially influenced by blood pressure in midlife using MRI scans from people in the UK Biobank registry. Then they examined the relationship between blood pressure and cognitive function in the UK Biobank registry. Next, of the brain structures affected by blood pressure, they identified those that are causally linked to cognitive impairment.

This was possible thanks to genetic markers coding for increased blood pressure, brain structure imaging phenotypes, and those coding for cognitive impairment that could be used in Mendelian randomization studies.

"We looked at 3935 brain magnetic resonance imaging–derived phenotypes in the brain and cognitive function defined by fluid intelligence score to identify genetically predicted causal relationships," Guzik said.

They identified 200 brain structures that were causally affected by systolic blood pressure. Of these, nine were also causally related to cognitive impairment. The results were validated in a second prospective cohort of patients with hypertension.

"Some of these structures, including putamen and the white matter regions spanning between the anterior corona radiata, anterior thalamic radiation, and anterior limb of the internal capsule, may represent the target brain regions at which systolic blood pressure acts on cognitive function," the authors comment.

In an accompanying editorial, Ernesto Schiffrin, MD, and James Engert, PhD, McGill University, Montreal, Canada, say that further mechanistic studies of the effects of blood pressure on cognitive function are required to determine precise causal pathways and the roles of relevant brain regions.

"Eventually, biomarkers could be developed to inform antihypertensive trials. Whether clinical trials targeting the specific brain structures will be feasible or if specific antihypertensives could be found that target specific structures remains to be demonstrated," they write.

"Thus, these new studies could lead to an understanding of the signaling pathways that explain how these structures relate vascular damage to cognitive impairment in hypertension, and contribute to the development of novel interventions to more successfully address the scourge of cognitive decline and dementia in the future," the editorialists conclude.

The study was funded by the European Research Council, the British Heart Foundation, and the Italian Ministry of Health.

European Heart Journal. Published online March 27, 2023. Full text, Editorial

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