Alzheimer’s and heart disease are two of the leading causes of death, both affecting millions of … [+]
Alzheimer’s and heart disease are two of the leading causes of death, both affecting millions of people around the world. Now, increasing studies have found that brain and heart health may be more connected than initially thought. At the interface between brain cells and blood vessels, the blood-brain barrier endures damage with age that seems to contribute to worsening cognitive function. In the most recent installment of this series on Alzheimer’s disease, we discussed the role that insulin receptors located in the blood-brain barrier may play in the development of Alzheimer’s. Here, we will delve deeper into the functions of the blood-brain barrier and how we may be able to prolong normal cognitive function in those with Alzheimer’s disease.
As we age, the blood-brain barrier develops tiny lesions that increase its permeability and impair function. Emerging studies have found that heightened dysfunction of the blood-brain barrier seems to occur early in the disease course, possibly before neurodegeneration, brain atrophy, and even cognitive symptoms. How this dysfunction contributes to Alzheimer’s disease has not been well understood, until now. A team from the Medical College of Georgia and collaborating institutions found that tiny lesions in the brain’s hair-thin microvascular vessels correspond with changes in white matter that ultimately contribute to worsening cognitive function and memory deficits.
What is white matter? Unlike gray matter which is comprised of neural cell bodies, white matter refers to the myelinated, or enclosed, axon fibers that facilitate the fast transmission of nerve impulses. White matter is essential for brain health and executing daily functions, including memory, problem-solving, and coordination. Not surprisingly, clinical observations have shown that changes in the brain’s white matter during Alzheimer’s disease correlate with memory deficits and impaired cognition.
In a previous report, the team identified a correlation between white matter deficits and blood-brain barrier dysfunction. It seems that the presence of tiny lesions within the microvessels of the blood-brain barrier generates oxidative stress and inflammation. Subsequent MRI imaging indicated that the increased inflammation may contribute to changes in the brain’s white matter.
To determine how blood-brain barrier dysfunction induces white matter changes in Alzheimer’s disease, Bagi et. al examined the brains of 28 people above the age of 65. This cohort included both men and women known to have Alzheimer’s disease, with or without obvious microvascular damage, in addition to healthy controls. They extracted white matter and cerebral vascular samples from the prefrontal cortex, a region of the brain that is particularly vulnerable to degeneration in Alzheimer’s disease.
Upon the first examination, investigators noted that cerebral blood vessels in those diagnosed with Alzheimer’s were significantly impaired. These blood vessels did not appear to dilate properly, even when exposed to powerful dilatation factors. The ability of blood vessels to dilate is critical for controlling the flow of blood across the blood-brain barrier. Impaired dilation not only may contribute to more inflammation and oxidative stress but also puts the blood vessels at risk of developing additional lesions.
Bagi et. al also found that greater impairment of the microvessels corresponded with more significant white matter changes. To their surprise, this was accompanied by an increased number of specific brain cells called astrocytes. As a key component of the blood-brain barrier, these supportive cells regulate the exchange of nutrients and waste between the brain and blood. Researchers speculate that with progressive microvascular dysfunction in Alzheimer’s disease, astrocytes undergo changes that cause them to become more reactive and inflammatory. The additional injury that these cells inflict on the brain-brain barrier and nearby cells makes the brain more vulnerable to cognitive changes.
Overall, this study adds to the growing body of evidence that inflammation within the blood-brain barrier induces structural changes in the brain. Fortunately, unlike neurodegeneration, vascular inflammation can be modified through diet and exercise. Dr. Zsolt Bagi, lead author and biologist at the Medical College of Georgia, wrote, “We are proposing that if you prevent development of the microvascular component, you may at least add several years of more normal functioning to individuals with Alzheimer’s.” Understanding the connection between heart and brain health may one day enable early screening for Alzheimer’s and other forms of dementia through routine blood tests.