Lower serum osteocalcin concentrations are associated with brain microstructural changes and worse cognitive performance

Rodent models have found that osteocalcin crosses the blood-brain barrier and regulates behaviour. No data are available on osteocalcin's effects on brain microstructure and cognitive performance in humans. We evaluated the association between serum osteocalcin concentrations and (i) brain microstructural changes on magnetic resonance imaging (MRI) and (ii) neuropsychological performance.We studied 24 consecutive obese subjects (13 women; age, 49·8 ± 8·1 years; body mass index [BMI], 43·9 ± 4·54 kg/m(2) ) and 20 healthy volunteers (10 women; age, 48·8 ± 9·5 years; BMI, 24·3 ± 3·54 kg/m(2) ) in a cross-sectional study within the multicentre FLORINASH Project. FLAIR signal intensity and DTI-metrics (primary (λ1 ), secondary (λ2 ) and tertiary (λ3 ) eigenvalues; fractional anisotropy (FA); and mean diffusivity) in the caudate, hypothalamus, thalamus and putamen, and in subcortical white matter were assessed. Cognitive performance evaluated by neuropsychological test battery.Lower osteocalcin concentrations were associated with BMI, higher λ1, λ2 and λ3 values at the caudate and lower FLAIR signal intensity at the caudate and putamen. Obese patients with lower osteocalcin concentrations had higher FA at putamen and thalamus. Lower osteocalcin concentrations were associated with higher Iowa Gambling Task (IGT) scores. FLAIR signal intensity at the caudate601·832 yielded 85·7% sensitivity, 64·3% specificity, 70·6% negative predictive value and 81·8% positive predictive value for IGT score. Lower osteocalcin was an independent predictor of worse cognitive performance on multivariate analysis (F = 3·551, P = 0·01343; R(2) = 0·103). Bayesian information criterion demonstrated that osteocalcin had the predominant role in predicting IGT score.Lower serum osteocalcin concentrations are associated with brain microstructural changes and worse cognitive performance.