Higher levels of inflammation in young adulthood are linked to lower performance on skills tests in midlife. Young adults with elevated levels of inflammation associated with obesity, physical inactivity, chronic disease, stress and smoking may have lower cognitive performance in midlife, a new UC San Francisco study shows. Researchers had previously linked higher levels of inflammation in older adults to dementia, but this is one of the first studies to link inflammation in early adulthood to lower cognitive abilities in midlife.

How Lifestyle Affects Cognitive Abilities

According to first author Amber Bahorik, PhD, of the UCSF Department of Psychiatry and Behavioral Sciences and the Weill Institute for Neurosciences, it is known from long-term studies that brain changes leading to Alzheimer’s and other dementias can take decades to develop. The researchers wanted to find out whether health and lifestyle habits in early adulthood play a role in cognitive abilities in midlife, which in turn can influence the likelihood of dementia later in life.

In their study, published in the journal Neurology, the experts found that only 10% of those with low inflammation performed poorly on tests of processing speed and memory, compared to 21% and 19% of those with moderate or higher levels of inflammation, respectively. When the researchers accounted for factors such as age, physical activity and total cholesterol levels, the differences in processing speed persisted; the researchers also found differences in executive function, which includes working memory, problem solving and impulse control.

The study followed 2,364 adults as part of the CARDIA study, which aims to identify those factors in young adulthood that lead to cardiovascular disease two to three decades later. Participants were between 18 and 30 years old when they were enrolled in the study and were tested four times over an 18-year period for the inflammatory marker C-reactive protein (CRP). The cognitive tests were carried out five years after the last CRP measurement, at which point most of the participants were in their forties and fifties. About half of the participants were female, slightly less than half were African American, and the rest were white. About 45% of participants had lower stable inflammation, while 16% had moderate or increasing inflammation; 39% had higher levels.

Inflammation and Health Risks

The researchers also linked higher levels of inflammation to physical inactivity, higher BMI and current smoking. Inflammation plays an important role in cognitive aging and can begin in early adulthood. There is likely a direct and indirect effect of inflammation on cognition.

Kristine Yaffe MD, Professor of Psychiatry and Behavioral Sciences, Neurology, and Epidemiology and Biostatistics at UCSF is a member of the first team of experts to find that 30% of dementia risk is preventable. Her recent research examined the link between irregular sleep and decreased cognition in midlife, as well as the impact of individual health and lifestyle changes on preventing memory loss in higher-risk older adults. Fortunately, there are ways to reduce inflammation – such as increasing physical activity and quitting smoking – that could be promising avenues for prevention.

Inflammation Plays a Role in Various Forms of Dementia

Previous research has already shown that inflammation in the brain is significantly involved in dementia. Inflammation is usually the body’s response to injury and stress, such as redness and swelling associated with an injury or infection. Inflammation in the brain – known as neuroinflammation – has been linked to many conditions, including depression, psychosis and multiple sclerosis. It has also been linked to the risk of Alzheimer’s disease.

In a study published in the journal Brain, a team of researchers from the University of Cambridge investigated whether neuroinflammation also occurs in other forms of dementia, which would mean that it is present in many neurodegenerative diseases. The team recruited 31 patients with three different forms of frontotemporal dementia (FTD). FTD is a family of different diseases caused by the accumulation of several abnormal “junk” proteins in the brain.

Patients underwent brain scans to detect inflammation and junk proteins. In each of two positron emission tomography (PET) scans, a chemical dye was injected to light up specific molecules that visualize either the brain’s inflammatory cells or the junk proteins. In the first scan, the dye illuminated the cells that cause neuroinflammation. These indicate ongoing damage to the brain cells and their connections. In the second scan, the dye binds to the different types of “junk” proteins found in FTD.

The researchers showed that throughout the brain and in all three types of FTD, the greater the inflammation in each part of the brain, the greater the damaging accumulation of junk proteins. To prove that the dyes detect the inflammation and harmful proteins, they analyzed under the microscope 12 brains that were donated to the Cambridge Brain Bank after death. The team emphasizes that further research is needed to translate knowledge about inflammation in dementia into testable treatments.

It is an important discovery that all three types of frontotemporal dementia have inflammation associated with the accumulation of harmful abnormal proteins in different parts of the brain. The diseases are also very different from each other in other ways. Together with the fact that inflammation is known to play a role in Alzheimer’s disease, the findings suggest that inflammation is part of many other neurodegenerative diseases, including Parkinson’s disease and Huntington’s disease. This raises hope that immune-based treatments could help slow or prevent these.