Age- and Sex-Different Associations between Cognitive Performance and Inflammatory Biomarkers in Community Dwelling Older Adults: towards Precision Preventive Strategies

BACKGROUND Studies have demonstrated associations between inflammatory biomarkers and cognitive function in people with dementia or stroke, but little is known regarding these associations in healthy middle-aged and older populations. OBJECTIVES This study aims to examine associations between inflammatory biomarkers (both vascular and systemic) and cognitive performance in stroke- and dementia-free middleaged and older adults without apolipoprotein E4 (ApoE e4) allele carriers. DESIGN A cross-sectional study. SETTING Social Environment and Biomarkers of Aging Study (SEBAS) 2006. PARTICIPANTS A total of 983 participants aged 53 years and older. MEASUREMENTS Composite cognitive function assessment, including the Short Portable Mental Status Questionnaire, the Rey Auditory Verbal Learning Test, and the Wechsler Adult Intelligence Scale. Overnight venous blood sampling for 6 inflammatory biomarkers (C-reactive protein, interleukin-6, fibrinogen, homocysteine, intercellular adhesion molecule-1 and E-selectin) and ApoE genotyping. RESULTS Among 983 participants (mean age: 65.8 +/- 9.5 years), 808 were non-ApoE epsilon 4 allele carriers and were stroke- and dementia-free. Higher log fibrinogen was associated with poorer cognitive function after adjustment for potential confounding factors in non-ApoE epsilon 4 allele carriers and strokeand dementia-free populations (unstandardized coefficients beta= -1.553, P value= 0.003). In participants aged 65 years or older, both of elevated fibrinogen and homocysteine were associated with poorer cognitive function (beta= -2.288, P value= 0.015; beta= -1.331, P value= 0.012, respectively). Elevated log CRP was significantly associated with lower cognitive function only in women (beta= -0.514, P value= 0.024). CONCLUSION Higher serum levels of fibrinogen were negatively associated with cognitive function, which was independent of ApoE genotyping and prior cerebrovascular events in dementia-free community-dwelling older adults. Further studies are needed to validate the roles of fibrinogen in the pathophysiology of dementia and elucidate the underlying mechanisms.