Fetuin-A, a new vascular biomarker of cognitive decline in older adults

Fetuin-A is an abundant plasma protein known to predict vascular disease. Fetuin-A levels are lower in patients with Alzheimer's disease in proportion to the severity of cognitive impairment, but their association with normal cognitive ageing is unknown. We evaluated the association of serum fetuin-A levels with cognitive function in community-dwelling older adults.

A population-based study of 1382 older adults (median age 75) who had plasma fetuin-A levels and cognitive function evaluated in 1992-1996; 855 had repeat cognitive function assessment a median of 4 years later.

Adjusting for age, sex, education and depression, higher levels of fetuin-A were associated with better baseline performance on the Mini-Mental Status Exam (MMSE; P = 0·012) and a tendency for better Trails Making B scores (P = 0·066). In longitudinal analyses, the likelihood of a major decline (highest decile of change) in Trails B was 29% lower (P = 0·010) for each SD higher baseline fetuin-A level; odds of major decline in MMSE was 42% lower (P = 0·005) per SD higher fetuin-A for individuals with no known CVD, but were not related to fetuin-A in those with CVD (P = 0·33). Fetuin-A was not related to Category Fluency performance. Results were independent of multiple vascular risk factors and comorbid conditions.

Higher plasma fetuin-A concentrations are associated with better performance on tests of global cognitive function and executive function and with less likelihood of major decline in these cognitive abilities over a 4-year period. Fetuin-A may serve as a biological link between vascular disease and normal age-related cognitive decline.