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

Summary Objectives Fetuin‐ A is an abundant plasma protein known to predict vascular disease. Fetuin‐ A levels are lower in patients with A lzheimer'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. Design/Patients/Measurements 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. Results Adjusting for age, sex, education and depression, higher levels of fetuin‐ A were associated with better baseline performance on the M ini‐ M ental S tatus E xam ( MMSE ; P  =   0·012) and a tendency for better T rails M aking B scores ( P  =   0·066). In longitudinal analyses, the likelihood of a major decline (highest decile of change) in T rails 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 C ategory F luency performance. Results were independent of multiple vascular risk factors and comorbid conditions. Conclusions 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.