Jacoba A van de Kreeke1, H Ton Nguyen1, Elles Konijnenberg2, Jori Tomassen2, Anouk den Braber2, Mara Ten Kate2, Carole H Sudre3,4, Frederik Barkhof5, Dorret I Boomsma6, H Stevie Tan1, Frank D Verbraak1, Pieter Jelle Visser2. 1. Ophthalmology Department, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands. 2. Alzheimer Center, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands. 3. School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom. 4. Dementia Research Centre, Institute of Neurology, University College London, London, United Kingdom. 5. Radiology Department, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands. 6. Department of Biological Psychology, Vrije Universiteit Amsterdam, Netherlands Twin Register, Amsterdam, Netherlands.
Abstract
Purpose: Retinal microvasculopathy may reflect small vessel disease in the brain. Here we test the relationships between retinal vascular parameters and small vessel disease, the influence of cardiovascular risk factors on these relationships, and their common genetic background in a monozygotic twin cohort. Methods: We selected 134 cognitively healthy individuals (67 monozygotic twin pairs) aged ≥60 years from the Netherlands Twin Register for the EMIF-AD PreclinAD study. We measured seven retinal vascular parameters averaged over both eyes using fundus images analyzed with Singapore I Vessel Assessment. Small vessel disease was assessed on MRI by a volumetric measurement of periventricular and deep white matter hyperintensities. We calculated associations between RVPs and WMH, estimated intratwin pair correlations, and performed twin-specific analyses on relationships of interest. Results: Deep white matter hyperintensities volume was positively associated with retinal tortuosity in veins (P = 0.004) and fractal dimension in arteries (P = 0.001) and veins (P = 0.032), periventricular white matter hyperintensities volume was positively associated with retinal venous width (P = 0.028). Intratwin pair correlations were moderate to high for all small vessel disease/retinal vascular parameter variables (r = 0.49-0.87, P < 0.001). Cross-twin cross-trait analyses showed that retinal venous tortuosity of twin 1 could predict deep white matter hyperintensities volume of the co-twin (r = 0.23, P = 0.030). Within twin-pair differences for retinal venous tortuosity were associated with within twin-pair differences in deep white matter hyperintensities volume (r = 0.39, P = 0.001). Conclusions: Retinal arterial fractal dimension and venous tortuosity have associations with deep white matter hyperintensities volume. Twin-specific analyses suggest that retinal venous tortuosity and deep white matter hyperintensities volume have a common etiology driven by both shared genetic factors and unique environmental factors, supporting the robustness of this relationship.
Purpose: Retinal microvasculopathy may reflect small vessel disease in the brain. Here we test the relationships between retinal vascular parameters and small vessel disease, the influence of cardiovascular risk factors on these relationships, and their common genetic background in a monozygotic twin cohort. Methods: We selected 134 cognitively healthy individuals (67 monozygotic twin pairs) aged ≥60 years from the Netherlands Twin Register for the EMIF-AD PreclinAD study. We measured seven retinal vascular parameters averaged over both eyes using fundus images analyzed with Singapore I Vessel Assessment. Small vessel disease was assessed on MRI by a volumetric measurement of periventricular and deep white matter hyperintensities. We calculated associations between RVPs and WMH, estimated intratwin pair correlations, and performed twin-specific analyses on relationships of interest. Results: Deep white matter hyperintensities volume was positively associated with retinal tortuosity in veins (P = 0.004) and fractal dimension in arteries (P = 0.001) and veins (P = 0.032), periventricular white matter hyperintensities volume was positively associated with retinal venous width (P = 0.028). Intratwin pair correlations were moderate to high for all small vessel disease/retinal vascular parameter variables (r = 0.49-0.87, P < 0.001). Cross-twin cross-trait analyses showed that retinal venous tortuosity of twin 1 could predict deep white matter hyperintensities volume of the co-twin (r = 0.23, P = 0.030). Within twin-pair differences for retinal venous tortuosity were associated with within twin-pair differences in deep white matter hyperintensities volume (r = 0.39, P = 0.001). Conclusions: Retinal arterial fractal dimension and venous tortuosity have associations with deep white matter hyperintensities volume. Twin-specific analyses suggest that retinal venous tortuosity and deep white matter hyperintensities volume have a common etiology driven by both shared genetic factors and unique environmental factors, supporting the robustness of this relationship.
Authors: Anmar Abdul-Rahman; William Morgan; Ying Jo Khoo; Christopher Lind; Allan Kermode; William Carroll; Dao-Yi Yu Journal: PLoS One Date: 2022-06-28 Impact factor: 3.752
Authors: Jurre den Haan; Jacoba A van de Kreeke; Bart N van Berckel; Frederik Barkhof; Charlotte E Teunissen; Philip Scheltens; Frank D Verbraak; Femke H Bouwman Journal: Alzheimers Dement (Amst) Date: 2019-05-10
Authors: Jacoba Alida van de Kreeke; Hoang-Ton Nguyen; Elles Konijnenberg; Jori Tomassen; Anouk den Braber; Mara Ten Kate; Maqsood Yaqub; Bart van Berckel; Adriaan A Lammertsma; Dorret I Boomsma; Stevie H Tan; Frank Verbraak; Pieter Jelle Visser Journal: Br J Ophthalmol Date: 2019-05-22 Impact factor: 4.638
Authors: Jacoba A van de Kreeke; Hoang-Ton Nguyen; Jurre den Haan; Elles Konijnenberg; Jori Tomassen; Anouk den Braber; Mara Ten Kate; Lyduine Collij; Maqsood Yaqub; Bart van Berckel; Adriaan A Lammertsma; Dorret I Boomsma; Hendra Stevie Tan; Frank D Verbraak; Pieter Jelle Visser Journal: Acta Ophthalmol Date: 2019-05-06 Impact factor: 3.761
Authors: Jacoba A van de Kreeke; Hoang Ton Nguyen; Elles Konijnenberg; Jori Tomassen; Anouk den Braber; Mara Ten Kate; Maqsood Yaqub; Bart van Berckel; Adriaan A Lammertsma; Dorret I Boomsma; H Stevie Tan; Pieter Jelle Visser; Frank D Verbraak Journal: Acta Ophthalmol Date: 2020-10-18 Impact factor: 3.761