Summary: According to a new study, people who have inflammation biomarkers in their blood during middle age are more likely to have increased brain shrinkage as they grow older. Researchers report the brain cell loss associated with inflammation was most prevalent in areas affected in Alzheimer’s disease.
People who have biomarkers tied to inflammation in their blood in their 40s and 50s may have more brain shrinkage decades later than people without the biomarkers, according to a study published in the November 1, 2017, online issue of Neurology. The brain cell loss was found especially in areas of the brain that are affected by Alzheimer’s disease.
“These results suggest that inflammation in mid-life may be an early contributor to the brain changes that are associated with Alzheimer’s disease and other forms of dementia,” said study author Keenan Walker, PhD, of Johns Hopkins University School of Medicine in Baltimore, Md. “Because the processes that lead to brain cell loss begin decades before people start showing any symptoms, it is vital that we figure out how these processes that happen in middle age affect people many years later.”
People with the inflammation markers and brain shrinkage also had lower scores on average on a memory test.
For the study, researchers tested the levels of five markers of inflammation in the blood, including the white blood cell count, in 1,633 people with an average age of 53. An average of 24 years later, the participants took a memory test and had brain scans to measure the volume of several areas of the brain.
The participants were divided into three groups based on how many elevated levels of inflammation they had among the five biomarkers.
Compared to the people with no elevated levels, people with elevated levels on three or more biomarkers had on average 5 percent lower volume in the hippocampus and other areas of the brain associated with Alzheimer’s disease.
Walker said that the effect of one standard deviation increase in the overall inflammation score in mid-life on brain volume decades later was similar to the effect associated with having one copy of the apolipoprotein E (APOE) e4 gene that increases the risk of Alzheimer’s disease.
Every standard deviation increase in the inflammation score was also associated with a hippocampus volume that was 110 cubic millimeters smaller and the volume of other areas affected by Alzheimer’s disease was 532 cubic millimeters smaller.
On the memory test, where people were asked to remember a list of 10 words, the people with no elevated markers remembered an average of about 5.5 words, while those with three or more elevated markers remembered an average of about five words.
Limitations of the study include that the biomarkers were measured only once. Walker said it’s not clear whether a single measurement can adequately determine that people have chronic inflammation.
Funding: Dr. Powell’s study was supported by funding from the National Institute of Child Health and Human Development, The Hartwell Foundation, Autism Science Foundation, Autism Speaks, BRAINS for Autism, and gifts from Debra Caudy and Clay Heighten.
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Original Research: Abstract for “Midlife systemic inflammatory markers are associated with late-life brain volume” by Keenan A. Walker, PhD, Ron C. Hoogeveen, PhD, Aaron R. Folsom, MD, MPH, Christie M. Ballantyne, MD, David S. Knopman, MD, B. Gwen Windham, MD, MHS, Clifford R. Jack Jr, MD and Rebecca F. Gottesman, MD, PhD in Neurology. Published online November 1 2017 doi:10.1212/WNL.0000000000004688
Midlife systemic inflammatory markers are associated with late-life brain volume
Objective: To clarify the temporal relationship between systemic inflammation and neurodegeneration, we examined whether a higher level of circulating inflammatory markers during midlife was associated with smaller brain volumes in late life using a large biracial prospective cohort study.
Methods: Plasma levels of systemic inflammatory markers (fibrinogen, albumin, white blood cell count, von Willebrand factor, and Factor VIII) were assessed at baseline in 1,633 participants (mean age 53  years, 60% female, 27% African American) enrolled in the Atherosclerosis Risk in Communities Study. Using all 5 inflammatory markers, an inflammation composite score was created for each participant. We assessed episodic memory and regional brain volumes, using 3T MRI, 24 years later.
Results: Each SD increase in midlife inflammation composite score was associated with 1,788 mm3 greater ventricular (p = 0.013), 110 mm3 smaller hippocampal (p = 0.013), 519 mm3 smaller occipital (p = 0.009), and 532 mm3 smaller Alzheimer disease signature region (p = 0.008) volumes, and reduced episodic memory (p = 0.046) 24 years later. Compared to participants with no elevated (4th quartile) midlife inflammatory markers, participants with elevations in 3 or more markers had, on average, 5% smaller hippocampal and Alzheimer disease signature region volumes. The association between midlife inflammation and late-life brain volume was modified by age and race, whereby younger participants and white participants with higher levels of systemic inflammation during midlife were more likely to show reduced brain volumes subsequently.
Conclusions: Our prospective findings provide evidence for what may be an early contributory role of systemic inflammation in neurodegeneration and cognitive aging.
“Midlife systemic inflammatory markers are associated with late-life brain volume” by Keenan A. Walker, PhD, Ron C. Hoogeveen, PhD, Aaron R. Folsom, MD, MPH, Christie M. Ballantyne, MD, David S. Knopman, MD, B. Gwen Windham, MD, MHS, Clifford R. Jack Jr, MD and Rebecca F. Gottesman, MD, PhD in Neurology. Published online November 1 2017 doi:10.1212/WNL.0000000000004688