title: Lower serum osteocalcin concentrations are associated with brain microstructural changes and worse cognitive performance.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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 caudate <601·832 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.
  
  
  CONCLUSIONS
  Lower serum osteocalcin concentrations are associated with brain microstructural changes and worse cognitive performance.
authors.affiliation: Department of Radiology (IDI), Research Unit, Girona Biomedical Research Institute (IDIBGI), Hospital Universitari de Girona Dr Josep Trueta, Girona, Spain.|Department of Computer Science, Applied Mathematics and Statistics, University of Girona, Girona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Puig
authors.affiliation: Department of Radiology (IDI), Research Unit, Girona Biomedical Research Institute (IDIBGI), Hospital Universitari de Girona Dr Josep Trueta, Girona, Spain.
authors.forename: Gerard
authors.initials: G
authors.lastname: Blasco
authors.affiliation: Department of Computer Science, Applied Mathematics and Statistics, University of Girona, Girona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Daunis-i-Estadella
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Girona Biomedical Research Institute (IDIBGI), Hospital Universitari de Girona Dr Josep Trueta, and CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Girona, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Moreno
authors.affiliation: Department of Radiology (IDI), Research Unit, Girona Biomedical Research Institute (IDIBGI), Hospital Universitari de Girona Dr Josep Trueta, Girona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Molina
authors.affiliation: Biomedical Imaging Research Group (GIBI230), La Fe Polytechnics and University Hospital, La Fe Health Research Institute, Valencia, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Alberich-Bayarri
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Girona Biomedical Research Institute (IDIBGI), Hospital Universitari de Girona Dr Josep Trueta, and CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Girona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Xifra
authors.affiliation: Department of Radiology (IDI), Research Unit, Girona Biomedical Research Institute (IDIBGI), Hospital Universitari de Girona Dr Josep Trueta, Girona, Spain.
authors.forename: Salvador
authors.initials: S
authors.lastname: Pedraza
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Girona Biomedical Research Institute (IDIBGI), Hospital Universitari de Girona Dr Josep Trueta, and CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Girona, Spain.
authors.forename: Wifredo
authors.initials: W
authors.lastname: Ricart
authors.affiliation: Department of Psychiatry, Hospital Universitari de Bellvitge, and CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Barcelona, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Fernández-Aranda
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Girona Biomedical Research Institute (IDIBGI), Hospital Universitari de Girona Dr Josep Trueta, and CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Girona, Spain.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Fernández-Real
mesh_terms: D000328:Adult; D016880:Anisotropy; D001499:Bayes Theorem; D015992:Body Mass Index; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D003071:Cognition / Q000502:physiology*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009483:Neuropsychological Tests; D009765:Obesity / Q000097:blood* / Q000503:physiopathology / Q000523:psychology; D015675:Osteocalcin / Q000097:blood*; D011237:Predictive Value of Tests
chemical_list: D015675:Osteocalcin