Peripheral Inflammation in a Canadian Cohort of Neurodegenerative Conditions: Occurrence, Determinants, and Impact

Background "Inflammaging" describes chronic low-grade inflammation observed in aging individuals. It may play a major role in neurodegeneration. Objective To assess blood inflammatory markers in older adults. We hypothesized that elevated inflammation would be found in some cognitively normal older adults but would be more prevalent in individuals with cognitive impairment. Methods 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. Results 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. Conclusions 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.