Blood tests may show dementia risk decades before symptoms appear

Published on Monday, August 9, 2021

By: Karen Bascom

New research from the University of Mississippi Medical Center shows that blood tests could provide an easier and earlier way to identify people most at-risk for cognitive impairment.

The research, published online August 4 in Neurology, the medical journal of the American Academy of Neurology, shows that higher blood plasma levels of an amyloid protein during midlife is associated with lower risk of dementia decades later.

The study is the latest to come from The MIND (Memory Impairment and Neurodegenerative Dementia) Center at UMMC, a leader in research and clinical care for patients with Alzheimer’s disease, dementia and other forms of cognitive decline.

Amyloid Precursor Protein is an abundant brain protein that is broken down into several different peptide variants. One variant, beta-amyloid, “accumulates in the brain and is a defining characteristic of Alzheimer’s disease,” said Dr. Kevin Sullivan, MIND Center researcher and first author of the study.

“It used to be that the only way to verify the presence of brain amyloid was through autopsy. Now we can estimate it through brain imaging or a lumbar puncture to sample the cerebrospinal fluid,” said Sullivan, an assistant professor of medicine at UMMC. “However, these procedures are invasive and expensive.”

Instead, Sullivan and The MIND Center team wanted to learn if blood samples could provide a cheaper, easier way to detect amyloid. The researchers were particularly interested in beta-amyloid 42, a “particularly sticky variant” that contributes to Alzheimer’s disease plaques.

“In a healthy brain, this protein is cleared into the cerebrospinal fluid and into the blood stream. Detecting a higher amount of this amyloid variant in the blood is actually a good sign in terms of dementia risk,” he said.

This research involved 2,284 participants selected from the Atherosclerosis Risk in Communities (ARIC) study. The scientists checked blood samples taken over a 25-year period for beta-amyloid 42 and beta-amyloid 40, a more abundant variant of this protein. Through medical records, cognitive test results, and expert determination the researchers classified participants with normal cognition, mild cognitive impairment or dementia, including Alzheimer’s disease, during late-life.

“We saw that higher plasma beta-amyloid 42 and higher plasma beta-amyloid 42:40 ratio were associated with significantly lower risk of dementia or mild cognitive impairment over the following 25 years,” Sullivan said. “In fact, midlife plasma beta-amyloid levels were actually more strongly associated with risk than late-life measurements.”

This suggests that blood-based testing might have additional utility in identifying early risk among relatively younger populations.

“Our findings are in line with other studies that suggest the pathological changes contributing to the development of dementia in late-life begin many years in advance of clinical symptoms,” said Dr. Gwen Windham of The MIND Center, a professor of medicine and co-author of the study.

The relationship was consistent across demographic factors, such as sex, education and race. It also held up when adjusted for other known dementia risk factors, such as diabetes and hypertension.

For 34 years, ARIC has followed its cohort, which includes thousands of Jackson residents, from midlife onward to learn more about cardiovascular health. Because of the study’s size, breadth of data and timeline, “ARIC is one of the very best cohorts in order to do this kind of research,” Sullivan said.

Next, the researchers want to test the usefulness of other blood biomarkers, such as plasma tau, “which is the protein that makes up the destructive tangles we see in Alzheimer’s pathology,” Sullivan said.

“The MIND Center’s new Study of Aging, in collaboration with the Mayo Clinic, will seek to validate these blood biomarkers,” Windham said.

These blood tests are “not quite at the point of clinical utility,” Sullivan said. That may be a few years away.

However, “Where we do see a chance for more immediate benefit is in clinical trials for drug development,” Sullivan said. “This would be a first use-case, where we can identify people who are at higher risk for developing dementia based on this biomarker, even if they are not experiencing symptoms.”

He expects an increased interest in Alzheimer’s disease-related trials, especially in the wake of the recent and controversial approval of Aduhelm.

Finding new screening methods and treatments will be especially important as the population ages, Sullivan said.

“Mississippi has an epidemic of Alzheimer’s disease and dementia in general, and the number of people with these conditions is increasing,” he said. “It’s becoming more and more important to find ways to stop or delay the onset of dementia. Even delaying the onset of dementia by just a few years would have enormous benefits for patients, their families and the health care system.”

Other study co-authors come from the Johns Hopkins University and the Mayo Clinic. The National Institutes of Health provided funding for this study.