Circulating interleukin-6 concentration and cognitive decline in old age: the PROSPER study

Area of Science:

• Gerontology
• Neuroscience
• Immunology

Background:

• Inflammation is implicated in the development of cardiovascular disease and cognitive decline.
• The role of Interleukin-6 (IL-6) in cardiovascular disease is established, but its direct association with cognitive decline remains unclear.
• Investigating the link between IL-6 levels, its genetic variations, and cognitive function in aging populations is crucial.

Purpose of the Study:

• To examine the association between high Interleukin-6 (IL-6) concentrations and cognitive decline in elderly individuals.
• To investigate the relationship between the IL-6 -174 promoter polymorphism and age-related cognitive decline.
• To determine if these factors are independent of cardiovascular disease status and risk factors.

Main Methods:

• Analysis of over 5000 participants (mean age 75) from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER).
• Baseline measurement of IL-6 concentrations and IL-6 -174 polymorphism genotypes (C allele associated with higher IL-6).
• Repeated cognitive testing over a mean follow-up of 39 months to assess executive function and memory.

Main Results:

• Higher IL-6 concentration correlated with poorer executive cognitive function cross-sectionally (P < 0.001) and prospectively (P = 0.002).
• Higher IL-6 concentration was associated with an increased rate of memory decline (P = 0.002) over time.
• The IL-6 -174 CC genotype showed an association with worse performance on the Stroop test (P = 0.045), independent of IL-6 levels.

Conclusions:

• Elevated circulating IL-6 levels are significantly associated with impaired cognitive function and accelerated cognitive decline in older adults.
• Preliminary genetic evidence suggests a potential causal link between the IL-6 pathway and cognitive decline.
• Further research into the IL-6 pathway's role in cognitive aging is warranted.