Heightened levels of brain inflammation biomarkers have been linked to the development of dementia, but it remains unclear whether inflammation must be present long-term in order to affect brain health.
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New research finds evidence that chronic inflammation may be tied to dementia.

Last year, Medical News Today reported on a study suggesting that elevated inflammation levels in midlife increased a person’s risk of experiencing loss of brain function and developing dementia later in life.

And recently, researchers from Johns Hopkins University in Baltimore, MD, have conducted a study analyzing data collected from 1,532 participants.

Of these, 61 percent were women and 28 percent were African-American.

Specifically, the team tracked levels of a blood biomarker of inflammation called C-reactive protein and looked at its relationship with the risk of dementia.

“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,” says lead researcher Keenan Walker.

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.”

Keenan Walker

The team’s findings are reported in the journal Neurobiology of Aging.

Inflammation and white matter damage

To gain a better understanding of how inflammation can affect an individual’s brain and cognitive abilities over a long period of time, Walker and colleagues looked at data collected through the Atherosclerosis Risk in Communities Study (ARIC), which examined cardiovascular risk factors among middle-aged and older people.

For the new study, the researchers evaluated participants’ brain structure, and to what extent its integrity was preserved over a period of 21 years from middle age to late life.

Alongside this, the investigators also assessed levels of the inflammation marker C-reactive protein, which is produced in the liver.

Throughout the 21-year period, the participants had five visits with ARIC researchers — around one every 3 years, on average. At their final follow-up visits, the participants had an average age of 76.

During the final visit, each person had an MRI scan to check for white matter damage. White matter — containing axons coated in a protective layer of myelin — is tasked with carrying information between nerve cells. In brain scans, white matter damage appears as intensely white patches.

At the second, fourth, and final visit, the researchers also collected blood samples from the participants, so that they could measure levels of inflammation.

Those who had under 3 milligrams per liter of C-reactive protein were judged to have low levels of inflammation throughout their bodies. Conversely, those with 3 milligrams per liter or more of the tell-tale biomarker were said to have high levels of inflammation.

Walker and colleagues’ analyses revealed that, of all the participants, the 90 individuals whose inflammation had increased to chronic (that is, persistently high) levels during midlife also presented the most white matter damage in the brain.

This remained valid even after potentially modifying factors — such as participants’ age, sex, levels of education, and risk of cardiovascular disease — were taken into account.

Furthermore, when the researchers looked at measurements of brain structural integrity, they also concluded that those participants who had elevated levels of C-reactive protein in middle age showed brain structure damage similar to that seen in people about 16 years older.

‘Inflammation may be a reversible factor’

Walker believes that the results obtained in this study suggest that there may be a cause and effect relationship between growing levels of inflammation in middle age that remain high until later in life and the development of dementia.

But, he cautions that this is still just an observational study, and more research into any underlying mechanisms is required in order to establish causality.

Walker explains that chronic inflammation is often caused by conditions such as cardiovascular disease, heart failure, hypertension, and diabetes, as well as particular infectious diseases, including HIV and hepatitis C.

Although inflammation also normally increases with age, he adds that certain factors — including poor overall health — could make it worse.

“Our work is important,” notes senior study author Dr. Rebecca Gottesman, “because currently there aren’t treatments for neurodegenerative diseases, and inflammation may be a reversible factor to prolong or prevent disease onset.”

“Now, researchers have to look at how we might reduce inflammation to reduce cognitive decline and neurodegeneration,” she concludes.

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