Association of Interleukin-6 and Interleukin-8 with Cognitive Decline in an Asian Memory Clinic Population

Abstract

Background: Neuroinflammation has been postulated to play an important role in cognitive impairment, cognitive decline, and dementia. Inflammatory biomarkers such as interleukin-6 (IL-6) and IL-8 are found to be associated with the neuro-inflammatory process and worse cognitive function. However, it is unknown whether these interleukins are associated with long-term cognitive function. Objective: To investigate the association of baseline IL-6 and IL-8 with cognitive function at baseline as well as its association with cognitive decline over five-year follow-up. Methods: 387 patients were recruited from an ongoing memory clinic-based study who underwent comprehensive physical, medical, neuropsychological and blood assessments together with brain MRI. IL-6 and IL-8 were measured using LUMINEX assays. The National Institute of Neurological Disorders and Stroke-Canadian Stroke Network neuropsychological battery was used to assess cognitive decline across multiple domains. Results: Among the 387 (mean age = 72.9 years and 53.7% males) participants, 322 had at least two follow-up assessments and were included in the longitudinal analysis. Negative linear trend associations were found between tertiles of IL-8 with baseline global cognition (p-trend< 0.001), attention (p-trend = 0.005), executive function (p-trend< 0.001), and visuospatial function (p-trend = 0.002) domains. No association was found between baseline IL-8 and cognitive decline. IL-6 was not associated with both baseline and follow-up cognition. Conclusion: IL-8 was associated with worse cognition especially in attention, executive function, and visuospatial function, suggesting the role of neuroinflammation in cognitive impairment. Hence, blood inflammatory biomarkers may be useful indicators in identifying patients at risk of cognitive impairment and warrant consideration for inclusion in treatment trials.