title: Angiographic evidence of proliferative retinopathy predicts neuropsychiatric morbidity in diabetic patients.
abstract: BACKGROUND
  Diabetic retinopathy (DR) is a common vasculopathy categorized as either non-proliferative (NPDR) or proliferative (PDR),characterized by dysfunctional blood-retinal barrier (BRB) and diagnosed using fluorescein angiography (FA). Since the BRB is similar in structure and function to the blood-brain barrier (BBB) and BBB dysfunction plays a key role in the pathogenesis of brain disorders, we hypothesized that PDR, the severe form of DR, is likely to mirror BBB damage and to predict a worse neuropsychiatric outcome.
  
  
  METHODS
  A retrospective cohort study was conducted among subjects with diabetes (N=2982) with FA-confirmed NPDR (N=2606) or PDR (N=376). Incidence and probability to develop brain pathologies and mortality were investigated in a 10-year follow-up study. We used Kaplan-Meier, Cox and logistic regression analyses to examine association between DR severity and neuropsychiatric morbidity adjusting for confounders.
  
  
  RESULTS
  Patients with PDR had significantly higher rates of all-cause brain pathologies (P<0.001), specifically stroke (P=0.005), epilepsy (P=0.006) and psychosis (P=0.024), and a shorter time to develop any neuropsychiatric event (P<0.001) or death (P=0.014) compared to NPDR. Cox adjusted hazard ratio for developing all-cause brain impairments was higher for PDR (HR=1.37, 95% CI 1.16-1.61, P<0.001) which was an independent predictor for all-cause brain impairments (OR 1.30, 95% CI 1.04-1.64, P=0.022), epilepsy (OR 2.16, 95% CI 1.05-4.41, P=0.035) and mortality (HR=1.35, 95% CI 1.06-1.70, P=0.014).
  
  
  CONCLUSIONS
  This is the first study to confirm that angiography-proven microvasculopathy identifies patients at high risk for neuropsychiatric morbidity and mortality.
authors.affiliation: Department of Physiology and Cell Biology, Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel; Department of Medical Neuroscience, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Yonatan
authors.initials: Y
authors.lastname: Serlin
authors.affiliation: Clinical Research Center, Soroka University Medical Center, Beer-Sheva, Israel.
authors.forename: Tali
authors.initials: T
authors.lastname: Shafat
authors.affiliation: Department of Ophthalmology, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Jaime
authors.initials: J
authors.lastname: Levy
authors.affiliation: Ophthalmology and Visual Sciences, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Aaron
authors.initials: A
authors.lastname: Winter
authors.affiliation: Department of Ophthalmology, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Marina
authors.initials: M
authors.lastname: Shneck
authors.affiliation: Department of Ophthalmology, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Boris
authors.initials: B
authors.lastname: Knyazer
authors.affiliation: Department of Industrial Engineering and Management, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Yisrael
authors.initials: Y
authors.lastname: Parmet
authors.affiliation: Department of Psychiatry, Soroka University Medical Center, Beer-Sheva, Israel.
authors.forename: Hadar
authors.initials: H
authors.lastname: Shalev
authors.affiliation: Division of Endocrinology and Metabolism, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Ehud
authors.initials: E
authors.lastname: Ur
authors.affiliation: Department of Physiology and Cell Biology, Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel; Department of Medical Neuroscience, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada. Electronic address: alon.friedman@dal.ca.
authors.forename: Alon
authors.initials: A
authors.lastname: Friedman
mesh_terms: D000792:Angiography; D001927:Brain Diseases / Q000453:epidemiology* / Q000401:mortality*; D015897:Comorbidity; D003930:Diabetic Retinopathy / Q000000981:diagnostic imaging / Q000453:epidemiology*; D005260:Female; D006801:Humans; D007557:Israel / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D015996:Survival Rate
keywords: Angiography; Blood-brain barrier; Blood-retinal barrier; Diabetic retinopathy; Neuropsychiatry