Microscopic disease of blood vessels in the brain’s white matter associated with worse cognition in Alzheimer’s – Jagwire

Disease of the microscopic blood vessels that feed the white matter of our brains is associated with poorer cognitive function and memory deficits in people with Alzheimer’s, scientists report.

“The main message of this article is that mixed pathology, as we call it, microvascular disease and Alzheimer’s, is associated with more brain damage, more white matter damage and more inflammation,” he says. Dr Zsolt Bagivascular biologist at Department of Physiology in the Medical College of Georgia a University of Augusta.

His and other recent findings suggest that some people with Alzheimer’s who have brain changes widely associated with the condition, such as amyloid plaques, may not develop dementia without this underlying vascular dysfunction, the researchers write in the journal. geroscience.

“We propose that if you prevent the development of the microvascular component, you can at least add several years of more normal functioning to people with Alzheimer’s,” says Bagi.

the and for Dr Stephen BackPediatric neurologist, Clyde and Elda Munson Professor of Pediatric Research and an expert in white matter injury and repair in the adult and developing brain at Oregon Health and Science University, are co-authors of the new study.

The good news is that vascular disease is potentially modifiable, Bagi says, by reducing major contributors like hypertension, obesity, diabetes and inactivity.

The scientists looked at the brains of 28 people who participated in the Study of Changes in the Thought of Adultsor ACT, a joint initiative of the Kaiser Permanente Washington Research Institute and the University of Washington, whose scientists also collaborated on the new study.

ACT is a longitudinal study of the cognitive health of community volunteers in the Seattle, Washington area, with the goal of finding ways to delay or prevent memory decline. Participants age 65 and older without cognitive impairments at enrollment are followed until death, with about 25% agreeing to autopsy and making genomic DNA from their blood and/or brain tissue available to scientists.

The individuals who served as controls for the study had no evidence of Alzheimer’s or vascular disease in the brain. Other groups had Alzheimer’s without vascular disease, vascular disease without markers of Alzheimer’s, or both Alzheimer’s and vascular disease.

Their focus in the studies was white matter, which makes up about 50 percent of brain mass, allows different brain regions to communicate, and is packed with long arms called axons that connect neurons to each other and to other cells throughout the brain. Body. as muscle cells. Another focus was the microscopic arterioles that directly feed the white matter with blood, oxygen, and nutrients.

They wanted to test their theory that when these hair-thin arterioles had difficulty dilating and supporting this part of the brain, white matter changes occurred that were evident on sophisticated MRIs, especially when microvascular problems co-existed with the more classic brain. . Alzheimer’s disease changes.

They found that the arterioles of those who had been diagnosed with Alzheimer’s and dysfunction of these tiny arteries had a reduced ability to dilate in response to the powerful blood vessel dilator bradykinin, compared to those without obvious microvascular dysfunction. Dilation problems were associated with white matter injury and changes in white matter structure that were visible on MRI.

Expression of the precursor to nitric oxide, also a potent blood vessel dilator, was also reduced in these individuals with both conditions, while expression of the superoxide generated by NOX1, which damages blood vessels, was increased.

Dysfunction of the arterioles was also associated with more white matter lesions as visible on those sophisticated MRI scans and higher numbers of brain cells, called astrocytes, that support neurons.

The researchers had previously reported an increase in these astrocytes in the brain with microvascular changes. This time they saw that when both Alzheimer’s and microvascular changes were present, astrocytes became more reactive, inflammatory and damaging.

Colleagues at Oregon Health and Science University, led by Back, looked at the same brain tissue with a sophisticated MRI technique called diffusion tensor imaging, which uses the diffusion of water between cells to look at the microstructure of the brain. white matter and its connectivity.

They couldn’t see the individual arterioles because they are too small (about 30 microns, or 0.0011811 inches) to see without a microscope. But they were able to see the white matter damage that resulted from disease of the arterioles, and again they found the correlation between vascular damage and tissue damage that Bagi described by directly visualizing the tissue. This type of blood vessel disease was present in 50% of the brains they studied, and other autopsy studies have indicated a similarly high rate.

In those with fewer indicators of brain changes, they found that the arterioles were better able to dilate and that the brain area had better connectivity and less apparent damage on postmortem MRI.

Impaired dilation ability of these small vessels in the white matter is known to be associated with white matter injury, such as that seen on specialized magnetic resonance imaging. And there is evidence from both laboratory and human studies that this vascular dysfunction not only worsens, but also plays a role in the development of cognitive decline and dementia in people with Alzheimer’s, the researchers write.

In fact, vascular dysfunction may be present before brain tissue damage and cognitive dysfunction are evident. In research animals bred to develop Alzheimer’s disease, for example, there is evidence of problems with the microvasculature in areas of the brain associated with Alzheimer’s disease, such as the hippocampus, a center of learning and memory, at a very young age.

The new work confirms the growing concept that small blood vessel disease can help predict the severity of dementia and/or the use of MRI DTI can help identify those patients with disease early enough that Strategies to slow or slow small blood vessel disease may help slow or slow your cognitive loss. The technique could also help assess the potential benefit of the intervention.

“These people could especially benefit from exercising, monitoring their blood sugar and controlling their blood pressure,” says Bagi.

Some patients with Alzheimer’s disease are known to have white matter hyperintensities on MRI, basically damaged areas that appear particularly bright on the scan and are associated with conditions such as dementia. A significant proportion of people with Alzheimer’s also have conditions such as high blood lipid levels and hypertension that are known to affect the function of blood vessels, including the smaller vasculature, Bagi notes. Disease of the small blood vessels in the brain is also common in aging and can indicate an increased risk of problems such as stroke or dementia. Sophisticated brain scans also often indicate microinfarcts, essentially microscopic strokes, which also tend to increase with age and are associated with memory decline.

According to the Alzheimer’s Organization. Then there are those genes that can directly cause Alzheimer’s disease, called deterministic genes, which affect the production or processing of beta-amyloid, the main component of plaque associated with Alzheimer’s disease, but even having these rare genes is not sickness guarantee.

“You have a certain genetic predisposition, but people realize that not everyone develops memory impairment or cognitive deficits unless something else comes up,” says Bagi. He notes that they have not yet analyzed the genes for this study.

Next steps include studying the associations they found in more human brains and further studies to better understand exactly how small blood vessel disease occurs, which could point to new targets for intervention.

The research was supported by the National Institute on Aging at the National Institutes of Health and the National Institute of Neurological Disorders and Stroke and the Nancy and Buster Alvord Foundation. The scientists also thanked the ACT study participants “whose dedication to supporting critical human research” made the published work possible.

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