Conference Coverage

High Systemic Inflammation at Midlife Portends Cognitive Changes in Later Life

Systemic inflammation may have an early pathogenic role in the cognitive decline that occurs before older adulthood.


ATLANTA—Individuals with higher levels of systemic inflammation during midlife experience greater rates of cognitive decline over the subsequent 20-year period, according to results from a long-term analysis presented at the 143rd Annual Meeting of the American Neurological Association.

“There is considerable evidence suggesting that abnormal immune functioning and inflammation may influence cognitive functioning and promote dementia,” said lead study author Keenan Walker, PhD, a clinical neuropsychology postdoctoral fellow at the Johns Hopkins University School of Medicine in Baltimore. “For example, several studies have found higher levels of inflammatory markers in the blood and CSF of patients with dementia, compared to nondemented individuals of a comparable age. What is less clear, however, is whether inflammation actually promotes cognitive decline or occurs simply as a result of the brain changes underlying dementia.”

Keenan Walker, PhD

To help answer this question, Dr. Walker and his colleagues evaluated blood biomarkers of inflammation in 12,727 middle-aged participants during visits one and two of the Atherosclerosis Risk in Communities (ARIC) study, a prospective epidemiologic analysis conducted in four US communities and funded by the National Heart, Lung, and Blood Institute. Visit 1 occurred between 1987 and 1989, and Visit 2 took place between 1990 and 1992. The researchers related these markers to cognitive change over the subsequent decades. Specifically, they used four biomarkers (ie, fibrinogen, white blood cell count, von Willebrand factor, and Factor VIII) to create an inflammation composite score at Visit 1 and measured C-reactive protein (CRP) at Visit 2. Next, they used measures of memory, executive function, and language to assess cognition over three visits spanning 20 years.

The average age of study participants at the first cognitive assessment was 57, 56% were women, and 21% were black. After controlling for differences in demographic variables, vascular risk factors, and comorbidities, the researchers observed that each standard deviation (SD) increase in the midlife inflammation composite score was associated with an additional 20-year global cognitive decline of 0.035 SD. They found a similar association between each SD higher midlife CRP level and additional 20-year decline in global cognition (0.038 SD). In addition, study participants with a midlife inflammation composite score in the top quartile had a 7.6% steeper decline in global cognition, compared with participants in the lowest quartile. A similar association was observed for CRP.

“We were surprised at what we found when we looked at inflammation’s effect on individual cognitive domains,” said Dr. Walker. “Specifically, we found that inflammation was associated with declines in memory, but not declines in other domains, such as executive function or language. One possible interpretation for these findings is that inflammation may selectively influence brain regions such as the hippocampus that are necessary for memory consolidation and are also most vulnerable to Alzheimer’s disease.” He added that the current findings “provide support for the idea that systemic inflammation may have an early pathogenic role in the cognitive decline that occurs in the decades leading up to older adulthood.”

Dr. Walker acknowledged certain limitations of the study, including the attrition of participants because of deaths and dropouts over the 20-year follow-up period. “Because high levels of inflammation and comorbid disease are related to death and risk of study dropout, the sample of participants who completed the entirety of the study may represent a group that is healthier overall than the general population,” he said. “However, we took several steps to reduce any potential attrition bias using advanced statistical techniques.”

—Doug Brunk

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