Mid- to late-life increases in marker of chronic inflammation tied to dementia

July 2, 2018, Johns Hopkins University School of Medicine
Brain scans showing white matter damage. Credit: Gottesman lab

Researchers at Johns Hopkins have added to evidence that rising and chronic inflammation as measured by a biomarker in the blood in middle and late age are linked to visible structural changes in the brains of people with poor cognition and dementia.

The authors say results of their study, based on data gathered from a federally funded study on more than 1,500 people, suggests that efforts to curb with drugs or lifestyle changes midlife or earlier may be key to delaying or preventing cognitive decline in old age.

"We found that individuals who had an increase in inflammation during midlife that was maintained from mid to late life have greater abnormalities in the 's white matter structure, as measured with MRI scans," says Keenan Walker, Ph.D., lead author and postdoctoral fellow in the Department of Neurology at the Johns Hopkins University School of Medicine.

"This suggests to us that inflammation may have to be chronic, rather than temporary, to have an adverse effect on important aspects of the brain's structure necessary for cognitive function," he adds.

Researchers have long gathered evidence that chronic inflammation and the biochemicals associated with it may damage the brain. C-reactive protein, an inflammatory factor made in the liver, for example, already has become a marker for chemical damage to heart and blood vessel tissue indicative of heart attack.

So far, however, according to Walker, studies linking inflammation to brain abnormalities have not looked at these factors and features over an extended period of time in the same population.

In their new study, described in the August issue of Neurobiology of Aging, Walker and his colleagues took data from the atherosclerosis risk in communities (ARIC) study that looked at brain structure and integrity, as well as a marker of inflammation over a 21-year period spanning middle age to late life.

Specifically, the investigators focused on and compared data on 1,532 participants recruited from 1987 to 1989 from Washington County, Maryland; Forsyth County, North Carolina; Minneapolis, Minnesota; and Jackson, Mississippi. Sixty-one percent of participants were women, and 28 percent were African-American. At the final visit, participants were an average age of 76.

Over the course of the ARIC study, each participant had five visits with study coordinators, averaging every three years. At the last visit, each participant underwent an MRI of their brain to examine evidence of damage to so-called white matter—the part of the brain responsible for transmitting messages. Damaged white matter appears superwhite on a scan, similar to overexposure on a photograph, and was measured using an automated program.

At visits 2, 4 and 5, the researchers took blood samples to measure for high-sensitivity C-reactive protein, a standard measure of inflammation throughout the body. Those with levels below 3 milligrams per liter were considered to have low inflammation, whereas those with 3 or more milligrams per liter of C-reactive protein were considered to have elevated inflammation.

Even after adjusting for demographics (e.g., sex and education) and cardiovascular disease risk, the researchers found that the 90 people who transitioned from low to persistently elevated C-reactive protein during midlife, indicating increasing inflammation, showed the greatest damage to the white matter in the brain.

Using a program that measures structural integrity at the microscopic level, the researchers estimate that the brains of the people who had escalating C-reactive protein in middle age appear similar to that of a person 16 years older.

Walker says because their findings overall showed that increasing and chronic inflammation were associated with the most damage to white matter, there is more reason to infer a cause and effect relationship between growing and persistent inflammation and evidence of dementia. But he emphasized that theirs was an "observational" study not designed to determine cause and effect, or to prove it. More studies would need to be done to prove cause and effect and figure out the precise pathways to brain damage, he added.

"Our work is important because currently there aren't treatments for neurodegenerative diseases, and inflammation may be a reversible factor to prolong or prevent disease onset," says Rebecca Gottesman, M.D., Ph.D., senior author and professor of neurology and epidemiology at Johns Hopkins. "Now, researchers have to look at how we might reduce inflammation to reduce cognitive decline and neurodegeneration."

Walker says that common causes of include cardiovascular disease, heart failure, diabetes, high blood pressure and infections such as hepatitis C or HIV. He also says that inflammation is a normal byproduct of aging, but poor physical health and injuries seem to exacerbate it.

Some studies suggest that reducing inflammation in the short term can be accomplished by treating and controlling common cardiovascular diseases and maintaining a healthy weight.

Explore further: Mid-life chronic inflammation may be linked to frailty later

More information: Keenan A. Walker et al. The association of mid-to late-life systemic inflammation with white matter structure in older adults: The Atherosclerosis Risk in Communities Study, Neurobiology of Aging (2018). DOI: 10.1016/j.neurobiolaging.2018.03.031

Related Stories

Mid-life chronic inflammation may be linked to frailty later

April 26, 2018
A study of nearly 6,000 Americans followed for 24 years from middle to late adulthood found that having chronic inflammation in middle age may be linked to an increased risk of frailty and overall poorer health decades later.

Inflammation in midlife linked to brain shrinkage later

November 1, 2017
People who show signs of inflammation in middle age are more likely to suffer from brain shrinkage later in life, a possible precursor to dementia or Alzheimer's disease, researchers said Wednesday.

Tending to heart health may keep dementia at bay

June 26, 2018
There's no definitive evidence about what can prevent Alzheimer's disease. But experts believe healthy behaviors that are good for your overall health can slow or delay some forms of dementia.

Immune system dysfunction may occur early in Alzheimer's disease

February 6, 2018
An association between inflammation biomarkers in both blood plasma and cerebrospinal fluid (CSF) and markers of Alzheimer's disease (AD) associated pathology, has been found by researchers at the University of Colorado Anschutz ...

Chronic inflammation linked to less likelihood of healthy aging

September 16, 2013
Chronic exposure to high levels of interleukin-6 was associated with a significantly lower likelihood of healthy aging, according to a study in CMAJ (Canadian Medical Association Journal).

New leads on treating dementia and Alzheimer's

May 2, 2018
A new study by scientists in Australia and the US provides an explanation for why clinical trials of drugs targeting proteins in the brain that were thought to cause dementia and Alzheimer's have failed. The study has opened ...

Recommended for you

Nicotine mimics may have therapeutic effect on inflammatory diseases

July 12, 2018
Stanford researchers discovered that a receptor that binds to nicotine and to clusters of beta-amyloid molecules is found on certain types of immune cells that can act as suppressors and regulators of the immune system.

Study shows BPA risk factor for inflammatory bowel disease

July 5, 2018
A recent study in a preclinical model of inflammatory bowel disease shows dietary exposure to bisphenol-A, or BPA, found in polycarbonate plastics and epoxy resins, can increase mortality and worsen its symptoms.

Mid- to late-life increases in marker of chronic inflammation tied to dementia

July 2, 2018
Researchers at Johns Hopkins have added to evidence that rising and chronic inflammation as measured by a biomarker in the blood in middle and late age are linked to visible structural changes in the brains of people with ...

Research team diagnoses asthma with nasal brush test

June 11, 2018
Mount Sinai researchers have identified a genetic biomarker of asthma that can be tested for using a simple nasal brush and basic follow-up data analysis. This inexpensive diagnostic test can accurately identify mild to moderate ...

Eosinophilic esophagitis may be due to missing protein

June 7, 2018
Scientists have discovered that the absence of a specific protein in cells lining the esophagus may cause inflammation and tissue damage in people with eosinophilic esophagitis (EoE). EoE affects as many as 150,000 people ...

Mouse study links triclosan, a common antimicrobial, to colonic inflammation

May 30, 2018
A large research team led by senior author Guodong Zhang at the University of Massachusetts Amherst reports that the antimicrobial ingredient triclosan, found in hand soaps and toothpastes among other products, could have ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.