title: Glucose indices are associated with cognitive and structural brain measures in young adults.
abstract: OBJECTIVE
  To evaluate the possible early consequences of impaired glucose metabolism on the brain by assessing the relationship of diabetes, fasting blood glucose (FBG) levels, and insulin resistance with cognitive performance and brain integrity in healthy young and middle-aged adults.
  
  
  METHODS
  The sample included dementia-free participants (mean age 40 ± 9 years; 53% women) of the Framingham Heart Study third-generation cohort with cognitive testing of memory, abstract reasoning, visual perception, attention, and executive function (n = 2,126). In addition, brain MRI examination (n = 1,597) was used to determine white matter, gray matter, and white matter hyperintensity (WMH) volumes and fractional anisotropy measures. We used linear regression models to assess relationships between diabetes, FBG, and insulin resistance with cognition, lobar gray matter, and WMH volumes as well as voxel-based microstructural white matter integrity and gray matter density, adjusting for potential confounders. Mediating effect of brain lesions on the association of diabetes with cognitive performance was also tested.
  
  
  RESULTS
  Diabetes was associated with worse memory, visual perception, and attention performance; increased WMH; and decreased total cerebral brain and occipital lobar gray matter volumes. The link of diabetes with attention and memory was mediated through occipital and frontal atrophy, and the latter also through hippocampal atrophy. Both diabetes and increased FBG were associated with large areas of reductions in gray matter density and fractional anisotropy on voxel-based analyses.
  
  
  CONCLUSIONS
  We found that hyperglycemia is associated with subtle brain injury and impaired attention and memory even in young adults, indicating that brain injury is an early manifestation of impaired glucose metabolism.
authors.affiliation: From the Department of Neurology (G.W., J.J.H., A.S.B., R.A., P.A.W., S.S.), Boston University School of Medicine, MA; The Framingham Heart Study (G.W., J.J.H., A.S.B., R.A., P.A.W., S.S.), MA; the Department of Neurology (P.M., C.D.), The University of California at Davis, Sacramento; and the Department of Biostatistics (A.S.B.), Boston University School of Public Health, MA. galitwai@bu.edu.
authors.forename: Galit
authors.initials: G
authors.lastname: Weinstein
authors.affiliation: From the Department of Neurology (G.W., J.J.H., A.S.B., R.A., P.A.W., S.S.), Boston University School of Medicine, MA; The Framingham Heart Study (G.W., J.J.H., A.S.B., R.A., P.A.W., S.S.), MA; the Department of Neurology (P.M., C.D.), The University of California at Davis, Sacramento; and the Department of Biostatistics (A.S.B.), Boston University School of Public Health, MA.
authors.forename: Pauline
authors.initials: P
authors.lastname: Maillard
authors.affiliation: From the Department of Neurology (G.W., J.J.H., A.S.B., R.A., P.A.W., S.S.), Boston University School of Medicine, MA; The Framingham Heart Study (G.W., J.J.H., A.S.B., R.A., P.A.W., S.S.), MA; the Department of Neurology (P.M., C.D.), The University of California at Davis, Sacramento; and the Department of Biostatistics (A.S.B.), Boston University School of Public Health, MA.
authors.forename: Jayandra J
authors.initials: JJ
authors.lastname: Himali
authors.affiliation: From the Department of Neurology (G.W., J.J.H., A.S.B., R.A., P.A.W., S.S.), Boston University School of Medicine, MA; The Framingham Heart Study (G.W., J.J.H., A.S.B., R.A., P.A.W., S.S.), MA; the Department of Neurology (P.M., C.D.), The University of California at Davis, Sacramento; and the Department of Biostatistics (A.S.B.), Boston University School of Public Health, MA.
authors.forename: Alexa S
authors.initials: AS
authors.lastname: Beiser
authors.affiliation: From the Department of Neurology (G.W., J.J.H., A.S.B., R.A., P.A.W., S.S.), Boston University School of Medicine, MA; The Framingham Heart Study (G.W., J.J.H., A.S.B., R.A., P.A.W., S.S.), MA; the Department of Neurology (P.M., C.D.), The University of California at Davis, Sacramento; and the Department of Biostatistics (A.S.B.), Boston University School of Public Health, MA.
authors.forename: Rhoda
authors.initials: R
authors.lastname: Au
authors.affiliation: From the Department of Neurology (G.W., J.J.H., A.S.B., R.A., P.A.W., S.S.), Boston University School of Medicine, MA; The Framingham Heart Study (G.W., J.J.H., A.S.B., R.A., P.A.W., S.S.), MA; the Department of Neurology (P.M., C.D.), The University of California at Davis, Sacramento; and the Department of Biostatistics (A.S.B.), Boston University School of Public Health, MA.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Wolf
authors.affiliation: From the Department of Neurology (G.W., J.J.H., A.S.B., R.A., P.A.W., S.S.), Boston University School of Medicine, MA; The Framingham Heart Study (G.W., J.J.H., A.S.B., R.A., P.A.W., S.S.), MA; the Department of Neurology (P.M., C.D.), The University of California at Davis, Sacramento; and the Department of Biostatistics (A.S.B.), Boston University School of Public Health, MA.
authors.forename: Sudha
authors.initials: S
authors.lastname: Seshadri
authors.affiliation: From the Department of Neurology (G.W., J.J.H., A.S.B., R.A., P.A.W., S.S.), Boston University School of Medicine, MA; The Framingham Heart Study (G.W., J.J.H., A.S.B., R.A., P.A.W., S.S.), MA; the Department of Neurology (P.M., C.D.), The University of California at Davis, Sacramento; and the Department of Biostatistics (A.S.B.), Boston University School of Public Health, MA.
authors.forename: Charles
authors.initials: C
authors.lastname: DeCarli
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D001927:Brain Diseases / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D048909:Diabetes Complications / Q000097:blood / Q000473:pathology / Q000503:physiopathology; D003920:Diabetes Mellitus / Q000097:blood*; D005260:Female; D066128:Gray Matter / Q000473:pathology; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008875:Middle Aged; D066127:White Matter / Q000473:pathology; D055815:Young Adult
chemical_list: D001786:Blood Glucose