IL-6 as a Measure of Peripheral Inflammation is More Often Elevated in Cognitively Impaired Individuals
The immune system is a very complex array of interacting cell populations, constantly changing over time. The inflammatory response is similarly complex, arising from many different inciting events and cascades of signaling and interaction between various immune cell types. Thus there are no simple measures of inflammation, no matter that the medical community has certainly tried very hard to make that goal a reality. Or perhaps it is better to say that simple measures of, say, one signaling molecule (in practice often C-reactive protein), paint a limited picture of what is actually going on. Sometimes that limited picture is useful, sometimes it is misleading.
Today's open access paper is a good illustration of the limits of what one can learn from a single marker, or two related markers. Circulating C-reactive protein and IL-6 are linked mechanistically in that C-reactive protein rises in response to IL-6. These are also the most commonly used measures of inflammation, so the research and medical communities have a fair grasp on the limitations. Nonetheless because they are commonly assessed markers, there is a tendency to continue to use them, as then at least there is a large body of existing data to compare against.
"Inflammaging" describes chronic low-grade inflammation observed in aging individuals. It may play a major role in neurodegeneration. Interleukin-6 (IL-6) and C-reactive protein (CRP) were assessed in 514 Canadian individuals in COMPASS-ND, a detailed study of cognitive impairment in the elderly. Cumulative link model (CLM) was used to investigate the relationship between inflammation status (low, medium, or high tertiles) and demographic and lifestyle factors along with cognitive function and cognitive diagnoses.
We found that 12% of cognitively normal older adults had IL-6 levels in the highest tertile, but this increased in cognitively impaired cohorts - 36% in Alzheimer's disease, 55% mixed dementia, 30% mild cognitive impairment, and 39% vascular mild cognitive impairment. We found that 36% of cognitively unimpaired older individuals display "elevated" IL-6 (middle and high tertile values), while approximately 70% of those with cognitive impairment also do so. Inflammation markers increased most robustly in association with age, higher body mass index, and higher Fazekas (MRI white matter hyperintensity) score. There were also weaker associations with female sex, nutrition, number of comorbidities, and poor sleep.
In conclusion, peripheral low-grade inflammation was common, particularly in individuals with cognitive impairment; and obesity and age were the main drivers. It remains unclear whether treatment targeting such inflammation might have a therapeutic role in dementia prevention.