2026

Peripheral inflammation in a Canadian cohort of neurodegenerative conditions: Occurrence, determinants, and impact

Authors:

Seixas-Lima, B., Rosa-Neto, P., Phillips, N. A., Borrie, M., Roncero, C. T., Lahiri, D., Dori, D., Eintracht, S., & Chertkow, H.

Journal:

Journal of Alzheimer's Disease

Abstract

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.

Plain Language Summary

Research has shown that levels of inflammation in the body and the brain play a key role in how we age. The term “inflammaging” has even been coined to refer to chronic inflammation observed in aging individuals. We studied the role of inflammation in aging because it is not fully understood yet.

We investigated inflammation in the blood of aging participants with various degrees of cognitive impairment. We wanted to answer a number of key questions, one of them being if a certain type of inflammation (peripheral inflammation) is present in all aging individuals, or present in some aging individuals only.

We found a relationship between aging and inflammation, confirming the reality of inflammaging. We found that inflammation is common but not present for all types of neurodegenerative conditions.

Obesity, poor nutrition and poor sleep are all risk factors for dementia that can modified with lifestyle adjustments. They were found to be at the core of inflammaging. Female sex, and increased cognitive impairment were also related to inflammation. Higher inflammation levels were found in individuals with vascular disease of the body and brain.

The role of inflammation is clear in the development and progression of neurodegeneration and dementia, but it is unclear whether treatments specifically targeting inflammation might have a role in preventing the development of dementia or other neurodegenerative diseases.

 

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