The blood-brain barrier is a specialized layer of cells surrounding blood vessels that pass through the central nervous system. It serves to separate the metabolism of the brain from the metabolism of the rest of the body by permitting passage of only certain molecules and cells to and from the brain. It is a complex system, and like all complex systems in biology, it falls apart with advancing age. This manifests as leakage, allowing inappropriate cells and molecules into the brain where they can provoke inflammation and other downstream issues. A growing consensus in the research community places blood-brain barrier dysfunction as an early contributing cause of neurodegenerative conditions and loss of cognitive function.
There is a weight of evidence in favor of the view presented above, obtained from a great many databases of human epidemiological data, as well as animal studies in which blood-brain barrier leakage is assessed. In today's open access paper the authors report on a human study that was set up to generate confirming data for the connection between blood-brain barrier dysfunction and cognitive decline. The results fall into line with other data indicating the importance of blood-brain barrier dysfunction in neurodegeneration.
Vascular risk factors, such as hypertension, high cholesterol, diabetes, and obstructive sleep apnea, have a well-established link to cerebrovascular pathology and accelerated cognitive decline. Vascular risk factors have been hypothesized to cause cerebrovascular disease via chronic hypoperfusion, which leads to a cascade of events that includes blood vessel injury (eg, fibrosis, hyalinosis), hypoxia, and ischemia. These mechanisms cause inflammation that disrupts the blood-brain barrier (BBB), resulting in white matter damage.
Some theories suggest that BBB permeability manifests earlier than structural brain changes and therefore may serve as an early marker of emerging neuropathological processes and cognitive dysfunction. This is supported in rodent models, in which BBB dysfunction has been linked to inflammation and precedes neuropathological processes, including neurodegeneration and cognitive decline and accumulation of β-amyloid, a protein associated with Alzheimer's disease (AD). Ultimately, cognitive dysfunction is a common end point of neurodegeneration that clinically manifests as a neurocognitive disorder. However, few studies have examined theoretical models of the involvement of BBB permeability in the cascade of events leading to neurocognitive impairment, including the relationships between vascular risk factors, BBB permeability, and cognitive dysfunction.
The purpose of this study was to investigate the relationship between blood-brain barrier (BBB) permeability and cognitive functioning in healthy older adults and individuals with neurodegenerative diseases. A total of 124 participants with Alzheimer disease, cerebrovascular disease, or a mix of Alzheimer's and cerebrovascular diseases, and 55 control participants underwent magnetic resonance imaging and neuropsychological testing. BBB permeability was measured with dynamic contrast-enhanced magnetic resonance imaging and white matter injury was measured using a quantitative diffusion-tensor imaging marker of white matter injury. Structural equation modeling was used to examine the relationships between BBB permeability, vascular risk burden, white matter injury, and cognitive functioning.
Vascular risk burden predicted BBB permeability and white matter injury. BBB permeability predicted increased white matter injury and increased white matter injury predicted lower cognitive functioning. The study provides empirical support for a vascular contribution to white matter injury and cognitive impairment, directly or indirectly via BBB permeability. This highlights the importance of targeting modifiable vascular risk factors to help mitigate future cognitive decline.
View the full article at FightAging
