Maintaining healthy brain function requires careful control of blood flow to the brain through small blood vessels, so as to support the delivery of oxygen and nutrients to regions that need it more due to being more active. Small vessel diseases (SVDs) of the brain are among the commonest causes of memory loss, involved in over 40% of dementia cases (mainly vascular dementia). Hypertension has been found to be the main risk factor for SVD development, with many clinical studies indicating that raised mid-life blood pressure is linked with cognitive decline in later life. However, treatments particularly aimed at treating SVDs are not around, as the mechanisms linking hypertension to memory disturbance have not yet been established.
Dementia resulting from SVDs of the brain is an epidemic on the rise, for which treatment doesn’t exist. As mentioned, hypertension is the leading risk factor for SVDs, but how hypertension damages the brain microcirculation is not clear. However, given the knowledge that a link exists, researchers at the University of Manchester working with researchers in the United States conducted a study to evaluate the therapeutic effects of the antihypertensive drug amlodipine on hypertension-induced deficits in the brain. They looked at blood flow in the brains of mice with high blood pressure and vascular damage in the brain, treated these mice with amlodipine over a period of 5 months, compared them against the control mice (not treated with amlodipine), and analysed the data produced from the study.
According to the results, the mice given amlodipine had better blood flow to more active areas of the brain. Their blood vessels were able to widen and expand, which let in more oxygen and nutrients to reach the areas of the brain that required it the most.
The researchers also discovered for the first time that high blood pressure decreases the activity of a protein called Kir2.1. This protein is present in cells lining the blood vessels and it increases blood flow to active areas of the brain that need it most. Through down-regulation/suppression of the function of this protein, due to chronic hypertension, this halts a vital mechanism by which the brain microcirculation detects local neuronal activity and increases local blood flow to regions that are more active. And so, when the activity of this protein is down-regulated, blood flow to areas of the brain where it’s needed decreases. However, amlodipine was found to restore the activity of Kir2.1 and protect the brain from the harmful effects of high blood pressure.
The way vascular dementia develops has always been a mystery until now, and as mentioned there are no treatments as of now. Patients are presenting with symptoms of vascular dementia earlier than ever before. However, given the results of this study and with further research, it’s becoming a possibility to potentially offer these patients a way of preventing the progression of this life-changing disease.
The researchers are now looking to trial amlodipine as a treatment for vascular dementia in humans. If successful, it would be the first clinically proven treatment for vascular dementia due to SVD and could be used in individuals with early signs of the condition to prevent further progression.
Original Paper: M Koide., O.F Harraz., F Dabetrand., et al. (2021) Differential restoration of functional hyperemia by antihypertensive drug classes in hypertension-related cerebral small vessel disease. The Journal of Clinical Investigation. DOI: 10.1172/JCI149029
Original Link: https://doi.org/10.1172/JCI149029
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Edited by: Sophie