Elevated blood pressure is a significant risk factor for mortality worldwide, contributing to cerebrovascular diseases and dementia. Studies have established that hypertension is causally associated with impaired cognitive performance, and increased BP causes long-term changes in the brain. However, identifying specific brain areas responsible for BP-dependent cognitive changes has been challenging.
Recently, promising advances in genetic tools have offered a new approach to identifying brain structures mediating the relationship between BP and cognitive function. The approach involved mapping brain structures influenced by BP using Mendelian randomization (MR) analysis, elucidating the effects of BP on cognitive function in well-powered datasets, and identifying brain structures that accompany the detrimental effects of elevated BP on cognitive function using MR analysis.
A new study published in the European Heart Journal has identified a set of specific brain structures that potentially respond to differences in systolic blood pressure (SBP) and found an effect of blood pressure on cognitive function. The study, which used a triangulation approach based on combined observational and genetic causal inference approaches, was conducted by researchers from the Institute of Psychiatry, Psychology & Neuroscience at King’s College London and published in the journal Circulation.
The researchers analyzed data from 3935 brain imaging datasets, looking for a relationship between SBP and a specific set of brain structures using genetic causal inference methods. They identified several brain structures, including putamen and white matter regions between the anterior corona radiata, anterior thalamic radiation, and anterior limb of the internal capsule, that may represent the target brain regions at which SBP acts on cognitive function.
The study then used prospective cohort and case-control data to confirm the identified damage pattern linked by genetic instruments to SBP. The results suggested that the effect of BP on cognitive performance may be mediated by specific white matter tracts, making the absolute total brain quantification of white matter hyperintensities a less sensitive indicator for this association in hypertension.
Furthermore, it was found that the structural changes in the brain occur mainly in response to the difference between SBP and diastolic blood pressure (DBP). Most volumetric brain changes were associated with pulse pressure (PP) and mutually adjusted SBP and DBP in the multivariable MR analysis. At the same time, the researchers identified several resting-state functional brains changes potentially responding to SBP or DBP rather than to PP.
The study supports a modest, potentially causal, detrimental effect of higher SBP and PP. The null effect of DBP on cognitive function observed in the univariable analysis is intriguing, as higher DBP became protective after adjusting for SBP. This may reflect the impact of arterial stiffening on increased pulsatility in the brain microvasculature with increased penetration of forward and backward traveling pressure waves, as previously associated with white matter hyperintensities.
While the study has identified a set of specific brain structures that potentially respond to differences in SBP and found an effect of blood pressure on cognitive function, several limitations should be considered when interpreting the results. Minor overlap of subjects in exposure and outcome GWAS characterized most MR analyses. This may have affected the power and precision of the MR estimates.
Additionally, the study included a relatively small sample size of hypertensive and normotensive subjects in whom no conventional radiological damage was evident in clinical routine magnetic resonance imaging. Further validation will require focused large-scale magnetic resonance imaging studies in hypertensive subjects. Despite these limitations, the study provides critical new insights into the relationship between blood pressure and brain function. It may help develop new interventions to prevent or treat cognitive decline in individuals with hypertension.
