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Systemic Inflammation Linked With Later Dementia

Inflammatory biomarkers could help to identify people at higher risk of developing dementia, a study suggested. 

A research team from the University of Manchester analysed data from the UK Biobank to follow up on previous research suggesting that inflammation might play a contributing role in the onset of dementia.

They noted that although the literature had reported potential involvement of inflammation in both cognitive performance and Alzheimer’s disease, studies had not been consistent. They therefore set out to investigate the relationship between a composite systematic inflammatory biomarker measure (leucocyte count and C-reactive protein, CRP) with cognitive performance measures across five domains measured both concurrently and 4 to 13 years later. They also correlated the inflammatory biomarker association with dementia diagnoses recorded in linked hospital and primary care records 3 to 11 years later. 

Participants were all free of dementia at the outset. After excluding existing cases and those with the APOE ε2 / APOE ε4 genotype, the final sample comprised 433,556 individuals.

Worse Cognitive Performance

The study, published in PLoS ONE, reported that elevated initial inflammatory biomarker levels were associated with worse performance on cognitive measures, including tasks related to prospective memory, fluid intelligence, reaction time, and numeric memory, both at baseline and 4 to 13 years later. In addition, higher inflammatory biomarkers were associated with an increased risk of receiving a dementia diagnosis 3 to 11 years later.

While the associations were small, they were statistically significant, the authors said, noting that they had accounted for various demographic and health factors, including APOE status, cardiovascular problems, and deprivation. 

Being in the highest compared with the lowest quartile for the inflammatory biomarker score was associated with around a 35% increased risk for dementia diagnosis (HR 1.349, CI 1.215–1.498) in the fully adjusted model (including APOE).

"Our results indicate that systemic inflammation may play a small but significant part in dementia pathophysiology, especially in vascular dementia," the researchers concluded. 

Lead author, geneticist Dr Krisztina Mekli PhD, a research associate at the University of Manchester, said: "This association of course does not mean causality, therefore further research is needed to understand and evaluate the potential mechanism." 

Other known biomarkers, such as APOE status, appear to have a stronger association with dementia - the HR for APOE was 2.624 (CI 2.443–2.818) in this study. However, measuring inflammatory biomarkers could be an additional useful tool to help to identify people at elevated risk of developing dementia in the near future, Dr Mekli said.

The study was funded by the Advantage Foundation.