title: Hypothalamic damage is associated with inflammatory markers and worse cognitive performance in obese subjects.
abstract: BACKGROUND
  Growing evidence implicates hypothalamic inflammation in the pathogenesis of diet-induced obesity and cognitive dysfunction in rodent models. Few studies have addressed the association between obesity and hypothalamic damage in humans and its relevance.
  
  
  OBJECTIVE
  This study aimed to determine markers of obesity-associated hypothalamic damage on diffusion tensor imaging (DTI) and to determine whether DTI metrics are associated with performance on cognitive testing.
  
  
  METHODS
  This cross-sectional study analyzed DTI metrics (primary [λ(1)], secondary [λ(2)], and tertiary [λ(3)] eigenvalues; fractional anisotropy; and mean diffusivity) in the hypothalamus of 24 consecutive middle-age obese subjects (13 women; 49.8 ± 8.1 y; body mass index [BMI], 43.9 ± 0.92 kg/m(2)) and 20 healthy volunteers (10 women; 48.8 ± 9.5 y; BMI, 24.3 ± 0.79 kg/m(2)).
  
  
  RESULTS
  measures: Hypothalamic damage assessed by DTI metrics and cognitive performance evaluated by neuropsychological test battery.
  
  
  RESULTS
  λ(1) values in the hypothalamus were significantly lower in obese subjects (P < .0001). The sensitivity, specificity, and positive and negative predictive values for obesity-associated hypothalamic damage by λ(1) < 1.072 were 75, 87.5, 83.3, and 80.7%, respectively. Patients with hypothalamic λ(1) < 1.072 had higher values of BMI, fat mass, inflammatory markers, carotid-intima media thickness, and hepatic steatosis and lower scores on cognitive tests. Combined BMI and alanine aminotransferase had the strongest association with hypothalamic damage reflected by λ(1) < 1.072 (area under the curve = 0.89).
  
  
  CONCLUSIONS
  DTI detects obesity-associated hypothalamic damage associated with inflammatory markers and worse cognitive performance. This study highlights the potential utility of λ(1) as a surrogate marker of obesity-associated hypothalamic damage.
authors.affiliation: Department of Radiology (J.P., G.B., X.M., S.P.), Girona Biomedical Research Institute (IDIBGI), Hospital Universitari de Girona Dr Josep Trueta. Girona, Spain; Department of Computer Science, Applied Mathematics and Statistics (J.D.-i.-E.), University of Girona. Girona, Spain; Department of Diabetes, Endocrinology and Nutrition (J.P., G.X., W.R., J.M.F.-R.), IDIBGI, Hospital Universitari de Girona Dr Josep Trueta, and CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn). Girona, Spain; and Department of Psychiatry (F.F.-A.), Hospital Universitari de Bellvitge, and CIBERobn, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Puig
authors.forename: Gerard
authors.initials: G
authors.lastname: Blasco
authors.forename: Josep
authors.initials: J
authors.lastname: Daunis-I-Estadella
authors.forename: Xavier
authors.initials: X
authors.lastname: Molina
authors.forename: Gemma
authors.initials: G
authors.lastname: Xifra
authors.forename: Wifredo
authors.initials: W
authors.lastname: Ricart
authors.forename: Salvador
authors.initials: S
authors.lastname: Pedraza
authors.forename: Fernando
authors.initials: F
authors.lastname: Fernández-Aranda
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Fernández-Real
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D059168:Carotid Intima-Media Thickness; D003071:Cognition / Q000502:physiology*; D003430:Cross-Sectional Studies; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D007031:Hypothalamus / Q000503:physiopathology*; D007249:Inflammation / Q000097:blood / Q000503:physiopathology* / Q000523:psychology; D008875:Middle Aged; D009483:Neuropsychological Tests; D009765:Obesity / Q000097:blood / Q000503:physiopathology* / Q000523:psychology; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers