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High systemic inflammation at midlife portends cognitive changes in later life



Individuals with higher levels of systemic inflammation during midlife experience greater rates of cognitive decline over the subsequent 20-year period, results from a long-term analysis showed.

Dr. Keenan Walker of Johns Hopkins University, Baltimore

Dr. Keenan Walker

“There is considerable evidence suggesting that abnormal immune functioning and inflammation may influence cognitive functioning and promote dementia,” lead study author Keenan Walker, PhD, said in an interview in advance of the annual meeting of the American Neurological Association. “For example, several studies have found higher levels of inflammatory markers in the blood and cerebral spinal fluid 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.”

To help answer this question, Dr. Walker, of Johns Hopkins University, Baltimore, 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 U.S. communities and funded by the National Heart, Lung, and Blood Institute. Visit one occurred between 1987 and 1989, while visit two took place between 1990 and 1992. The researchers related these markers to cognitive change over the subsequent decades. Specifically, they used four biomarkers (fibrinogen, white blood cell count, von Willebrand factor, and Factor VIII) to create an inflammation composite score at visit one, and measured C-reactive protein (CRP) at visit two. Next, they used measures of memory, executive function, and language assess cognition over three visits spanning 20 years.

The average age of study participants at first cognitive assessment was 57 years, 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 (P less than .01). They found a similar association between each SD higher midlife CRP level and additional 20-year decline in global cognition (–0.038 SD; P less than .01). 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,” Dr. Walker said. “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, which 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.”

Dr. Walker disclosed that he receives funding support from the National Institutes of Health.

Source: Walker et al. ANA 2018, Abstract 305.

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