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

S P Mooijaart¹, N Sattar, S Trompet

¹Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands. s.p.mooijaart@lumc.nl

Journal of Internal Medicine

|February 19, 2013

Summary

Higher interleukin-6 (IL-6) levels are linked to worse cognitive function and faster decline in older adults. This suggests IL-6 may play a causal role in age-related cognitive impairment.

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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.