A new study reveals that chronic inflammation — as measured by a biomarker in the blood in middle and later age — is tied to visible structural changes in the brains of people with poor cognition and dementia.
The findings, published in the journal Neurobiology of Aging, suggest that curbing inflammation with lifestyle changes or drugs in 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 brain’s white matter structure, as measured with MRI scans,” said 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 been gathering evidence that chronic inflammation and the biochemicals associated with it may damage the brain. C-reactive protein, an inflammatory factor produced in the liver, for example, has become a marker for chemical damage to heart and blood vessel tissue indicative of heart attack.
But 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.
For the current study, Walker and team analyzed data of 1,532 participants taken from the atherosclerosis risk in communities (ARIC) study. The research recorded participants’ brain structure and integrity, as well as a marker of inflammation over a 21-year period spanning middle age to late life.
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. During the final visit, each individual underwent an MRI of their brain to look for 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 high-sensitivity C-reactive protein, a standard measure of inflammation throughout the body. Participants with levels below 3 milligrams per liter were considered to have low inflammation, while those with 3 or more milligrams per liter were recorded as having elevated inflammation.
Even after adjusting for several factors, such as gender, education and cardiovascular disease risk, the results revealed 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.
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.
Because the study shows that increasing and chronic inflammation is associated with the most damage to white matter, it gives more reason to infer a cause and effect relationship between growing and persistent inflammation and evidence of dementia.
Still, the study was considered observational and not designed to determine cause and effect, nor to prove it. More studies would need to be conducted to prove cause and effect and figure out the precise pathways to brain damage, Walker said.
“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,” said 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 said common causes of chronic inflammation include cardiovascular disease, heart failure, diabetes, high blood pressure and infections such as hepatitis C or HIV. He also said that although inflammation is a normal byproduct of aging, poor physical health and injuries seem to make it worse.
Some research suggests that reducing inflammation in the short term can be accomplished by treating and controlling common cardiovascular diseases and maintaining a healthy weight.
Source: Johns Hopkins Medicine