Brain tissue requires a sizable supply of oxygen and nutrients in comparison to most other organs of the body, and is thus disproportionately affected by the age-related decline of the cardiovascular system. This vascular degeneration takes numerous forms: loss of capillary density in tissues; a reduced ability of the heart to pump blood uphill, particularly in heart failure patients; the stiffening and narrowing of major arteries, with consequent hypertension able to cause pressure damage to sensitive tissues; the breakdown of the blood-brain barrier, allowing harmful cells and molecules to leak into the brain. These mechanisms have a meaningful impact on the progression of neurodegenerative conditions such as Alzheimer's disease.
The brain depends on the continuous delivery of oxygen and energy substrates due to its high-energy demand and the lack of long-term energy storage. The cerebral vasculature is well suited for this purpose, where regional cerebral blood flow (rCBF) is tightly regulated and can adapt to match the local energy demands of the nervous tissue. While the topology, anatomy and signalling cascades of the cerebral vasculature is unique to serve its specialized functions, its vascular bed is connected to the general circulation of the body. Thus, any change in blood content (e.g., as part of haemostasis, inflammation or infection) or haemodynamic and biomechanical changes of central blood vessel will affect the cerebral vasculature. Conversely, alterations of the cerebral vessels might have systemic effects. We know that many brain diseases are associated with vascular dysfunctions.
Alzheimer's disease (AD) impairs cognition, memory, and language and causes dementia. AD is defined by deposition of fibrillar amyloid-β (Aβ) plaques and neurofibrillary tangles of hyperphospohorylated tau and neurodegeneration. Accumulating evidence has shown that cerebrovascular disease is a common comorbidity in the presence of AD - and can on its own cause cognitive impairment and dementia (known as vascular dementia) - that contributes additively to its symptomatology and lowers the threshold for the development of dementia. However, given the marked structural changes of the microvasculature, an alternative hypothesis has been proposed stating that vascular dysfunction causes AD-related neuropathology and cognitive impairment (the "vascular hypothesis of AD"). Today, the picture seems more complex and far from complete. It is believed that neuropathological and vascular pathways interact synergistically and feedback to each other to potentiate AD symptoms.
Cerebral vascular abnormalities are highly prevalent in AD patients and can result in cognitive impairment and dementia, and thus can add to the symptomatology caused by AD pathology. However, many vascular processes directly affect and modulate, and often proceed AD neuropathology, the most important one being blood-brain barrier (BBB) impairment and hemodynamic dysfunction. This implicates vascular dysfunction as an integral part of AD etiology and pathophysiology. The interaction is bidirectional, where AD neuropathology can also lead to changes in vascular function. In addition, many changes observed to occur at the cerebral vasculature are related to systemic vascular abnormalities, which occur during aging and can be accelerated and aggravated by cardiovascular diseases. Thus, the cerebral vasculature is the locus where multiple pathogenic processes converge and contribute to cognitive impairment. Strategies that promote vascular health by managing vascular risk factors, changes in life style, and medication can significantly reduce the prevalence of AD, which has been demonstrated in some smaller studies.