Reference
Ungvari, Z., Toth, P., Tarantini, S. et al. Hypertension-induced cognitive impairment: from pathophysiology to public health. Nat Rev Nephrol (2021).
At a glance
Hypertension is a serious medical condition and its prevalence increases with advancing age (as a matter of fact, it affects two thirds of people over the age of 60). It is also correlated with both cognitive impairment and the risk of developing Alzheimer’s disease. This occurs because high blood pressure impairs both the structure and functional integrity of the cerebral microcirculation, resulting in a poor blood supply to the brain. Together with this, processes associated with hypertension, such as neuroinflammation, induce the deposition of amyloids – misfolded proteins that accumulate in fibers and cause neuronal death – and are characteristic of Alzheimer’s disease. This review examines the pathophysiological features of hypertension in relation to cognitive decline, the possible biomarkers that allow a quick diagnosis, and the viable paths for optimal clinical management.
The context and the starting point
In the industrialized world, vascular cognitive impairment (a kind of dementia caused by lack of blood supply to the brain) and Alzheimer’s disease are the leading causes of disease in the elderly. These kinds of dementia represent an obstacle to healthy aging. Moreover, it is estimated that the number of those affected by these conditions could quadruple in the next 50 years. Arterial hypertension seems to be a key target for delaying the onset of dementia. This pathology is directly related to aging, is extremely widespread, and is also potentially modifiable. Hypertension appears to be associated with both the general aging process and the progression of cognitive decline that typically occurs in the elderly. How? The characteristic features of aging are associated with a failure in regulating blood flow in the vessels that supply the brain. Together with this, there is increased cellular damage, an increase in oxidative stress, and the occurrence of inflammatory processes caused by high blood pressure. All of these issues eventually lead to damage of the cerebral vessels, with general vascular aging and brain deterioration. Furthermore, chronic hypertension can also promote the development of atherosclerotic plaques in the larger cerebral arteries. These can impede cerebral blood flow and lead to cerebrovascular events, such as ischemia and stroke. All of these factors contribute to the cognitive decline associated with aging and need to be investigated in more detail.
The results
This review offers a thorough examination of the pathophysiological mechanisms in which dementia and hypertension are interrelated. With an eye towards healthy aging, it also provides ideas for the clinical management and prevention of both conditions. As for cognitive decline, hypertension over the long term leads to a malfunction of cerebral circulation, with consequent problems related to normal blood flow to the brain and damage at the microvascular level. In fact, hypertension is capable of causing pathological changes in the cerebral vessels which damage the internal structure, the architecture and the general function of the microcirculation. Such damage contributes to cerebral microhemorrhages, strokes and lesions of the white matter of the brain. Furthermore, the pathological processes associated with hypertension, including inflammation and cell damage due to oxidative stress, lead to the breakdown of the blood-brain barrier and a decrease in neurovascular coupling (the increased blood supply that normally occurs with brain activities). All of these factors are associated with vascular cognitive decline. As previously mentioned, hypertension also increases the risk factor for Alzheimer’s disease (it is estimated that, in people over 65, those with hypertension have twice the risk of developing this disease). In addition to the aforementioned microvascular damage, the potential mechanisms through which hypertension could induce the progression of this kind of dementia include oxidative stress, brain inflammation and the breakdown of the blood-brain barrier. Moreover, in the cerebral lymphatic system, hypertension has been shown to induce a reduced elimination of amyloid-β. This protein, when it aggregates and accumulates in the brain structures, can lead to neuronal death and development of the typical structures of Alzheimer’s disease. As a result of this evidence, it is clear from this review that the use of medications or lifestyle interventions that reduce blood pressure, in combination with treatments that promote microvascular health, could potentially prevent or delay cognitive decline in patients with hypertension.
What are the prospects
In the future, determining whether the control of blood pressure could indeed help prevent cognitive decline could substantially influence public health, possibly leading to innovative methods of dementia prevention. Combinations of pharmaceutical treatments and lifestyle interventions that lower blood pressure, along with interventions that reduce blood pressure variability and prevent sudden spikes in systolic pressure, should be evaluated in randomized clinical trials. Such trials should also evaluate the neurocognitive conditions of the enrolled patients. These findings could lead to the development of new therapeutic strategies aimed at reversing vascular damage induced by aging and hypertension, such as mitochondrial antioxidants, polyphenols and senolytic drugs.
