title: Brain iron overload, insulin resistance, and cognitive performance in obese subjects: a preliminary MRI case-control study.
abstract: OBJECTIVE
  The linkage among the tissue iron stores, insulin resistance (IR), and cognition remains unclear in the obese population. We aimed to identify the factors that contribute to increased hepatic iron concentration (HIC) and brain iron overload (BIO), as evaluated by MRI, and to evaluate their impact on cognitive performance in obese and nonobese subjects.
  
  
  METHODS
  We prospectively recruited 23 middle-aged obese subjects without diabetes (13 women; age 50.4 ± 7.7 years; BMI 43.7 ± 4.48 kg/m2) and 20 healthy nonobese volunteers (10 women; age 48.8 ± 9.5 years; BMI 24.3 ± 3.54 kg/m2) in whom iron load was assessed in white and gray matter and the liver by MRI. IR was measured from HOMA-IR and an oral glucose tolerance test. A battery of neuropsychological tests was used to evaluate the cognitive performance. Multivariate regression analysis was used to identify the independent associations of BIO and cognitive performance.
  
  
  RESULTS
  A significant increase in iron load was detected at the caudate nucleus (P < 0.001), lenticular nucleus (P = 0.004), hypothalamus (P = 0.002), hippocampus (P < 0.001), and liver (P < 0.001) in obese subjects. There was a positive correlation between HIC and BIO at caudate (r = 0.517, P < 0.001), hypothalamus (r = 0.396, P = 0.009), and hippocampus (r = 0.347, P < 0.023). The area under the curve of insulin was independently associated with BIO at the caudate (P = 0.001), hippocampus (P = 0.028), and HIC (P = 0.025). BIOs at the caudate (P = 0.028), hypothalamus (P = 0.006), and lenticular nucleus (P = 0.012) were independently associated with worse cognitive performance.
  
  
  CONCLUSIONS
  Obesity and IR may contribute to increased HIC and BIO being associated with worse cognitive performance. BIO could be a potentially useful MRI biomarker for IR and obesity-associated cognitive dysfunction.
authors.affiliation: Department of Radiology, Girona Biomedical Research Institute, Diagnostic Imaging Institute, Girona, Spain.
authors.forename: Gerard
authors.initials: G
authors.lastname: Blasco
authors.affiliation: Department of Radiology, Girona Biomedical Research Institute, Diagnostic Imaging Institute, Girona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Puig
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 Radiology, Girona Biomedical Research Institute, Diagnostic Imaging Institute, Girona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Molina
authors.affiliation: Diabetes, Endocrinology and Nutrition Group, Girona Biomedical Research Institute, Dr. Trueta University Hospital, and Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBERobn), Girona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Xifra
authors.affiliation: Department of Psychiatry, Hospital de Bellvitge-Institut d'Investigació Biomèdica de Bellvitge and Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBERobn), Barcelona, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Fernández-Aranda
authors.affiliation: Department of Radiology, Girona Biomedical Research Institute, Diagnostic Imaging Institute, Girona, Spain.
authors.forename: Salvador
authors.initials: S
authors.lastname: Pedraza
authors.affiliation: Diabetes, Endocrinology and Nutrition Group, Girona Biomedical Research Institute, Dr. Trueta University Hospital, and Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBERobn), Girona, Spain.
authors.forename: Wifredo
authors.initials: W
authors.lastname: Ricart
authors.affiliation: Nutren Group, Department of Experimental Medicine, Lleida Agri-Food Science and Technological Park-Biomedical Research Institute of Lleida-Universitat de Lleida, Lleida, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Portero-Otín
authors.affiliation: Diabetes, Endocrinology and Nutrition Group, Girona Biomedical Research Institute, Dr. Trueta University Hospital, and Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBERobn), Girona, Spain jmfreal@idibgi.org.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Fernández-Real
mesh_terms: D000328:Adult; D001921:Brain / Q000378:metabolism; D016022:Case-Control Studies; D003071:Cognition / Q000502:physiology*; D003430:Cross-Sectional Studies; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D007501:Iron / Q000378:metabolism; D019190:Iron Overload / Q000503:physiopathology*; D008099:Liver / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications*; D011446:Prospective Studies
chemical_list: D007328:Insulin; D007501:Iron