Approved research

Relationship between cerebral pulsatility and cognitive impairment and its mediation by small vessel disease, and the potential role of arterial stiffness.

Lay summary

Chronic damage to the small blood vessels deep in the brain is seen on MRI brain scans in half of patients over the age of 60, and almost all patients over the age of 80. It is thought to be responsible for up to a third of strokes and almost half of patients with dementia. However, this condition, 'small vessel disease,' is poorly understood, with no clear explanation for its cause and no specific treatment to prevent its progression or consequences. One potential explanation is that as we age, and especially if we have high blood pressure, the largest vessels in the body become stiffer, resulting in greater pulsations of the blood pressure, with increased pressure hitting the brain each time the heart beats and reduced blood flow between heart beats. This may directly cause injury to these small blood vessels in the brain. We have previously demonstrated these associations in a small population, but to reliably assess the strength of such associations and their potential role in causing disease, we need arger studies and studies with repeated measures over time. We would like to use the UK Biobank study data to assess in the largest population available whether increased pulsations in the brain are related to chronic damage to the brain on MRI scans and whether this is associated with declining cognitive function. Then we would assess whether arterial stiffness or systemic blood pressure pulsations is related to cognitive impairment. In patients who have had both brain imaging and systemic measures of arterial stiffness (arterial stiffness index, systemic pulse pressure) we will assess whether relationships between increased pulsations of blood flow to the brain and cognitive problems are due to underlying stiffness of blood vessels. This analysis will also use expertise and analysis methods that we have developed previously to measure pulsations of blood flow in the brain on brain scans from the UK Biobank project for the first time, to assess whether it is likely to be responsible for the increase in small vessel disease and cognitive problems. We will then compare the UK Biobank results with our population of 1000 high-risk patients, to assess whether these relationships predict the progession of small vessel disease and development of future cognitive problems. This will allow us to identify new treatment targets to reduce this devastating yet common condition.