Cognitive Decline and Markers of Inflammation and Hemostasis: The Edinburgh Artery Study

OBJECTIVES: To determine whether circulating markers of activated inflammation and hemostasis are associated with cognitive decline in older people. DESIGN: Prospective cohort study (Edinburgh Artery Study). SETTING: Eleven general practices in Edinburgh, Scotland. PARTICIPANTS: A sample of 452 men and women followed for 16 years. MEASUREMENTS: Biomarker data were collected in 1987/88, and cognitive assessment was first conducted in 1998/99, when the mean age of the sample +/- standard deviation was 73.1+/-5.0), and subsequently in 2002/03. Information was obtained on verbal declarative memory (Wechsler Logical Memory Test (LMT)), nonverbal reasoning (Raven's Standard Progressive Matrices), verbal fluency (Verbal Fluency Test), information processing speed (Wechsler Digit Symbol Test), and a general cognitive factor representing the variance common to the individual test scores. RESULTS: In age-adjusted analyses, plasma fibrinogen, interleukin-6 (IL-6), and intercellular adhesion molecule 1 (ICAM-1) were negatively associated with performance on all cognitive measures in 2002/03 except the LMT (correlation coefficients from -0.10 to -0.24). In multivariate analyses controlling for demographic characteristics, depression, and cardiovascular morbidity and risk factors, fibrinogen independently predicted 4-year decline in nonverbal reasoning (P<.05). Also, when cognitive change was estimated from peak prior level, IL-6 turned out to be inversely related to decline in information processing speed (P<.05). Similarly, ICAM-1 was associated with a greater decline in general cognitive ability (P<.05) and nonverbal ability (P<.05). CONCLUSION: Systemic markers of inflammation and hemostasis are associated with a progressive decline in general and specific cognitive abilities in older people, independent of major vascular comorbidity.