title: White matter hyperintensities in middle-aged adults with childhood-onset type 1 diabetes.
abstract: OBJECTIVE
  Although microvascular complications are common in type 1 diabetes mellitus (T1DM), few studies have quantified the severity, risk factors, and implications of cerebral microvascular damage in these patients. As life expectancy in patients with T1DM increases, patients are exposed to age- and disease-related factors that may contribute to cerebral microvascular disease.
  
  
  METHODS
  Severity and volume of white matter hyperintensities (WMH) and infarcts were quantified in 97 middle-aged patients with childhood-onset T1DM (mean age and duration: 50 and 41 years, respectively) and 81 non-T1DM adults (mean age: 48 years), concurrent with cognitive and health-related measures.
  
  
  RESULTS
  Compared with non-T1DM participants, patients had more severe WMH (Fazekas scores 2 and 3 compared with Fazekas score 1, p < 0.0001) and slower information processing (digit symbol substitution, number correct: 65.7 ± 10.9 and 54.9 ± 13.6; pegboard, seconds: 66.0 ± 9.9 and 88.5 ± 34.2; both p < 0.0001) independent of age, education, or other factors. WMH were associated with slower information processing; adjusting for WMH attenuated the group differences in processing speed (13% for digit symbol, 11% for pegboard, both p ≤ 0.05). Among patients, prevalent neuropathies and smoking tripled the odds of high WMH burden, independent of age or disease duration. Associations between measures of blood pressure or hyperglycemia and WMH were not significant.
  
  
  CONCLUSIONS
  Clinically relevant WMH are evident earlier among middle-aged patients with childhood-onset T1DM and are related to the slower information processing frequently observed in T1DM. Brain imaging in patients with T1DM who have cognitive difficulties, especially those with neuropathies, may help uncover cerebral microvascular damage. Longitudinal studies are warranted to fully characterize WMH development, risk factors, and long-term effects on cognition.
authors.affiliation: From the Department of Epidemiology, Graduate School of Public Health (K.A.N., T.J.O., J.C.Z., R.M.B., T.C., R.G.M., C.R.) and Department of Psychiatry, School of Medicine (C.M.R., H.J.A., J.R.J., J.R.), University of Pittsburgh, Pittsburgh, PA; and VeraLight Inc. (J.D.M.), Albuquerque, NM.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Nunley
authors.affiliation: From the Department of Epidemiology, Graduate School of Public Health (K.A.N., T.J.O., J.C.Z., R.M.B., T.C., R.G.M., C.R.) and Department of Psychiatry, School of Medicine (C.M.R., H.J.A., J.R.J., J.R.), University of Pittsburgh, Pittsburgh, PA; and VeraLight Inc. (J.D.M.), Albuquerque, NM.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Ryan
authors.affiliation: From the Department of Epidemiology, Graduate School of Public Health (K.A.N., T.J.O., J.C.Z., R.M.B., T.C., R.G.M., C.R.) and Department of Psychiatry, School of Medicine (C.M.R., H.J.A., J.R.J., J.R.), University of Pittsburgh, Pittsburgh, PA; and VeraLight Inc. (J.D.M.), Albuquerque, NM.
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Orchard
authors.affiliation: From the Department of Epidemiology, Graduate School of Public Health (K.A.N., T.J.O., J.C.Z., R.M.B., T.C., R.G.M., C.R.) and Department of Psychiatry, School of Medicine (C.M.R., H.J.A., J.R.J., J.R.), University of Pittsburgh, Pittsburgh, PA; and VeraLight Inc. (J.D.M.), Albuquerque, NM.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Aizenstein
authors.affiliation: From the Department of Epidemiology, Graduate School of Public Health (K.A.N., T.J.O., J.C.Z., R.M.B., T.C., R.G.M., C.R.) and Department of Psychiatry, School of Medicine (C.M.R., H.J.A., J.R.J., J.R.), University of Pittsburgh, Pittsburgh, PA; and VeraLight Inc. (J.D.M.), Albuquerque, NM.
authors.forename: J Richard
authors.initials: JR
authors.lastname: Jennings
authors.affiliation: From the Department of Epidemiology, Graduate School of Public Health (K.A.N., T.J.O., J.C.Z., R.M.B., T.C., R.G.M., C.R.) and Department of Psychiatry, School of Medicine (C.M.R., H.J.A., J.R.J., J.R.), University of Pittsburgh, Pittsburgh, PA; and VeraLight Inc. (J.D.M.), Albuquerque, NM.
authors.forename: John
authors.initials: J
authors.lastname: Ryan
authors.affiliation: From the Department of Epidemiology, Graduate School of Public Health (K.A.N., T.J.O., J.C.Z., R.M.B., T.C., R.G.M., C.R.) and Department of Psychiatry, School of Medicine (C.M.R., H.J.A., J.R.J., J.R.), University of Pittsburgh, Pittsburgh, PA; and VeraLight Inc. (J.D.M.), Albuquerque, NM.
authors.forename: Janice C
authors.initials: JC
authors.lastname: Zgibor
authors.affiliation: From the Department of Epidemiology, Graduate School of Public Health (K.A.N., T.J.O., J.C.Z., R.M.B., T.C., R.G.M., C.R.) and Department of Psychiatry, School of Medicine (C.M.R., H.J.A., J.R.J., J.R.), University of Pittsburgh, Pittsburgh, PA; and VeraLight Inc. (J.D.M.), Albuquerque, NM.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Boudreau
authors.affiliation: From the Department of Epidemiology, Graduate School of Public Health (K.A.N., T.J.O., J.C.Z., R.M.B., T.C., R.G.M., C.R.) and Department of Psychiatry, School of Medicine (C.M.R., H.J.A., J.R.J., J.R.), University of Pittsburgh, Pittsburgh, PA; and VeraLight Inc. (J.D.M.), Albuquerque, NM.
authors.forename: Tina
authors.initials: T
authors.lastname: Costacou
authors.affiliation: From the Department of Epidemiology, Graduate School of Public Health (K.A.N., T.J.O., J.C.Z., R.M.B., T.C., R.G.M., C.R.) and Department of Psychiatry, School of Medicine (C.M.R., H.J.A., J.R.J., J.R.), University of Pittsburgh, Pittsburgh, PA; and VeraLight Inc. (J.D.M.), Albuquerque, NM.
authors.forename: John D
authors.initials: JD
authors.lastname: Maynard
authors.affiliation: From the Department of Epidemiology, Graduate School of Public Health (K.A.N., T.J.O., J.C.Z., R.M.B., T.C., R.G.M., C.R.) and Department of Psychiatry, School of Medicine (C.M.R., H.J.A., J.R.J., J.R.), University of Pittsburgh, Pittsburgh, PA; and VeraLight Inc. (J.D.M.), Albuquerque, NM.
authors.forename: Rachel G
authors.initials: RG
authors.lastname: Miller
authors.affiliation: From the Department of Epidemiology, Graduate School of Public Health (K.A.N., T.J.O., J.C.Z., R.M.B., T.C., R.G.M., C.R.) and Department of Psychiatry, School of Medicine (C.M.R., H.J.A., J.R.J., J.R.), University of Pittsburgh, Pittsburgh, PA; and VeraLight Inc. (J.D.M.), Albuquerque, NM. rosanoc@edc.pitt.edu.
authors.forename: Caterina
authors.initials: C
authors.lastname: Rosano
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology*; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000473:pathology* / Q000523:psychology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D066127:White Matter / Q000473:pathology*