Yonatan Serlin1, Tali Shafat2, Jaime Levy3, Aaron Winter4, Marina Shneck3, Boris Knyazer3, Yisrael Parmet5, Hadar Shalev6, Ehud Ur7, Alon Friedman8. 1. 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. 2. Clinical Research Center, Soroka University Medical Center, Beer-Sheva, Israel. 3. Department of Ophthalmology, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel. 4. Ophthalmology and Visual Sciences, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada. 5. Department of Industrial Engineering and Management, Ben-Gurion University of the Negev, Beer-Sheva, Israel. 6. Department of Psychiatry, Soroka University Medical Center, Beer-Sheva, Israel. 7. Division of Endocrinology and Metabolism, University of British Columbia, Vancouver, British Columbia, Canada. 8. 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.
Abstract
INTRODUCTION: 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.
INTRODUCTION: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.