White matter microangiopathy is associated with poorer cognitive performance in Alzheimer’s disease

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Disorders of the microvessels that feed the white matter of the brain are associated with poorer cognitive function and memory deficits in Alzheimer’s patients.

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August University news on August 2

“The main message of this paper is that our Said mixed pathology — microangiopathy and Alzheimer’s disease — is associated with more brain damage, more white matter (WM) damage, and more inflammation,'” Augustus Dr Zsolt Bagi, a vascular biologist in the Department of Physiology at the Medical College of Georgia at Augusta University, said.

Researchers in Geriatric Science, the official journal of the American Anti-Aging Society (AGE) (< em>GeroScience), they and other recent findings suggest that cerebral changes in some Alzheimer’s patients, such as amyloid plaques, are broadly associated with the disease, without which a potential microvascular dysfunction and may not develop dementia.

The research was published on May 25, 2022 in the journal GeroScience: 7.5>

Bagi said: “We suggest that if the progression of microvascular disease is prevented, normal function in Alzheimer’s patients can be increased for at least a few years.”

He and Oregon Health & Science University (OHSU) Pediatric Neurologist, Clyde and Elda Munson Research Professor of Pediatrics, Developmental and Adult White Matter Injury and Repair Specialist Dr. Stephen Back is a co-corresponding author of the new study.

Bagi says the good news is that by reducing Vascular disease is modifiable by major factors such as lack of exercise.

Scientists looked at 28 people who participated in the Adult Changes in Thought Study (ACT). Brain, ACT is a joint study by the Kaiser Permanente Washington Research Institute and the University of Washington, whose scientists also collaborators of the new study.

ACT is a initiative for communities from the Seattle, Washington area A Longitudinal Study of Cognitive Health for Cognitive Healthstrong>Find ways to slow or prevent memory decline. Participants were 65 years or older, no cognitive problems at enrollment, they were followed to death, and approximately 25% agreed to autopsy > and provide their blood and/or brain tissue genomic DNA to scientists.

Individuals who served as the study control group had no signs of Alzheimer’s disease or vascular disease in their brains. Another group had Alzheimer’s disease but no vascular disease, vascular disease with no markers of Alzheimer’s disease, or both Alzheimer’s disease and vascular disease.

Their study focuses on white matter, which makes up about 50% of the brain’s mass, enables different areas of the brain to communicate and is packed with components called axes. The long arms of the protrusions connect neurons to each other and other cells throughout the body, such as muscle cells, and arterioles directly supply white matter with blood, oxygen and nutrients.

Dr Zsolt Bagi with co-authors Katie Anne Fopiano

Dr Yanna Tian >They wanted to test their theory that when these hair-thin arterioles struggle to expand and support this part of the brain, it can lead to complexmagnetic resonance imaging (MRI) Visible white matter changes especially when microvascular problems coexist with more classic Alzheimer’s brain changes.

They found that those with diagnosed Alzheimer’s disease and these tiny arterial dysfunctions had higher levels of Arterioles, their ability to dilate in response to the powerful vasodilator bradykinin, are indeed attenuated. Problems with dilation are associated with white matter damage and changes in white matter structure, which are visible on MRI.

The expression of the precursor of the equally powerful vasodilator nitric oxide was also reduced in both cases, while the expression of the superoxide-producing NOX1 Increased, this NOX1 damages blood vessels.

Arteriole dysfunction is also associated with more white matter damage, which is based on complex MRI scans and supporting neurons called asterisks The result of an increase in the number of brain cells of glial cells.

Researchers have previously reported that as microvessels change, astrocytes in the brain Plasma cells increase. This time, they found that when Alzheimer’s disease and microvascular lesions co-occur, astrocytes become more active, inflammatory and destructive.

Oregon Health and Science University colleagues, led by Back, observed using a sophisticated MRI technique called diffusion tensor imaging (DTI). In the same brain tissue, this technique uses intercellular water diffusion to observe the microstructure and connectivity of white matter.

They cannot see individual arterioles because they are too small (about 30µm) to see without a microscope. But they can see white matter damage from small arterial disease, and again found a correlation between blood vessel damage and tissue damage, Bagi by directly visualizing tissue describes this correlation. The vascular disease was present in 50% of the brains they studied, and other autopsy studies have shown similarly high rates.

They found that those with lower markers of brain changes were less able to dilate small arteries Better, better connectivity in this area of ​​the brain and less damage on postmortem MRI.

It is well known that impaired dilation of these small blood vessels in white matter is associated with white matter damage, as seen in specialized MRI scans. There is evidence in both laboratory studies and human experiments that this vascular dysfunction is not only exacerbated, but also contributes to cognitive decline and the development of dementia in Alzheimer’s patients, the researchers wrote. play a role in .

In fact, vascular dysfunction may exist before brain tissue damage and cognitive impairment are apparent. For example, in research animals bred with Alzheimer’s disease, there is evidence that the microvasculature of brain regions associated with Alzheimer’s disease develops at an early age , such as the hippocampus, a center for learning and memory.

This new study confirms a growing notion that small vessel disease may help predict the severity of dementia and/or use DTI MRI to help identify those patients whose disease is early enough, Strategies to reduce or slow small vessel disease may help delay or reduce their cognitive loss. This technique may also be useful in assessing the potential benefits of interventions.

Bagi said: “These people may especially benefit if they exercise and control their blood sugar levels and blood pressure.”

Some Alzheimer’s patients have white matter hyperintensity on MRI scans, basically damaged areas that appear particularly bright on scans and are associated with problems such as dementia . A significant portion of Alzheimer’s patients also suffer from conditions such as hyperlipidemia and hypertension, which are known to impair vascular function, including the smallest vascular system, Bagi noted. Small vessel disease in the brain is also common during aging and may indicate an increased risk of problems such as stroke or dementia. Complex brain scans also often show microinfarcts, essentially microstrokes, which also tend to increase with age and are associated with memory impairments .

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Source: Medical College of Georgia at Augusta University

Microscopic blood vessel disease in the brain’s white matter associated with worse cognition in Alzheimer’s


Bagi, Z., Kroenke, C.D., Fopiano, K.A. et al. Association of cerebral microvascular dysfunction and white matter injury in Alzheimer’s disease. GeroScience (2022). https://doi.org /10.1007/s11357-022-00585-5


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