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Peripheral Levels of Fibrinogen, C-Reactive Protein, and Plasma Viscosity Predict Future Cognitive Decline in Individuals Without Dementia

From the Centre for Population Health Sciences (R.E.M., M.C.S., G.D.M, F.G.R.K., J.F.P.), Department of Psychology (I.J.D.), Medical Research Council Centre for Cognitive Ageing and Cognitive Epidemiology (I.J.D., J.F.P.), University of Edinburgh, Scotland, UK; and the Division of Cardiovascular and Medical Sciences (G.D.O.L., A.R.), University of Glasgow, Scotland, UK.

Address correspondence and reprint requests to Riccardo E. Marioni, Centre for Population Health Sciences, Public Health Sciences Section, University of Edinburgh, Medical School, Teviot Place, Edinburgh, EH8 9AG, Scotland, UK. E-mail: R.E.Marioni{at}sms.ed.ac.uk

Objective: To determine whether circulating levels of the biomarkers C-reactive protein (CRP), fibrinogen, plasma viscosity, and hematocrit were associated with cognitive decline in middle-aged to elderly people.

Methods: Subjects consisted of 2312 men and women aged 50 to 80 years participating in the Aspirin for Asymptomatic Atherosclerosis Trial, all of whom were free of symptomatic cardiovascular disease at baseline. Biomarker levels and cognitive ability were measured at baseline with cognition assessed in all subjects using the Mill Hill Vocabulary Scale and in a subgroup of 504 persons using tests of memory, nonverbal reasoning, information processing speed, executive function, and mental flexibility. After 5 years, the five-test battery was administered to all participants and scores were used to derive a general cognitive ability factor.

Results: Baseline CRP and fibrinogen levels were associated negatively with age and sex-adjusted follow-up scores on the majority of the cognitive tests, and the general cognitive ability factor (correlations = –0.054 to 0.105, p < .05). In analyses adjusting for baseline cognitive scores, asymptomatic atherosclerotic disease, and cardiovascular risk factors, both markers predicted decline in several cognitive domains (excluding memory). Baseline plasma viscosity, but not hematocrit, was associated negatively with follow-up test scores for general cognitive ability, information processing speed, and mental flexibility (correlations = –0.050 to –0.098, p < .05) and with decline across the same domains (p < .05).

Conclusions: Increased circulating levels of CRP, fibrinogen, and elevated plasma viscosity predicted poorer subsequent cognitive ability and were associated with age-related cognitive decline in several domains, including general ability.

Key Words: inflammation • rheology • cognition • cognitive decline

Abbreviations: CRP = C-reactive protein; AAA = Aspirin for Asymptomatic Atherosclerosis; ABI = ankle-brachial index; AVLT = Auditory Verbal Learning Test; RAVENS = Raven’s Standard Progressive Matrices; DST = Digit Symbol Test; VFT = Verbal Fluency Test; TMT = Trail Making Test, Part B; MHVS = Mill Hill Vocabulary Scale; CVD = cardiovascular disease; BP = blood pressure; fib = fibrinogen.