Association of fractal dimension and other retinal vascular network parameters with cognitive performance and neuroimaging biomarkers: The Multi-Ethnic Study of Atherosclerosis (MESA)

Sally S Ong¹, Jeremy J Peavey², Kevin D Hiatt³, Christopher T Whitlow³, Rebecca M Sappington^{1

4}, Atalie C Thompson¹, Samuel N Lockhart², Haiying Chen⁵, Suzanne Craft², Stephen R Rapp⁶, Annette L Fitzpatrick⁷, Susan R Heckbert⁷, José A Luchsinger⁸, Barbara E K Klein⁹, Stacy M Meuer⁹, Mary Frances Cotch¹⁰, Tien Y Wong^{11

12}, Timothy M Hughes²

Affiliations

¹ Department of Ophthalmology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
² Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
³ Department of Radiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
⁴ Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
⁵ Department of Psychiatry and Behavioral Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
⁶ Biostatistics and Data Science, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
⁷ Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington, USA.
⁸ Departments of Medicine and Epidemiology, Columbia University Irving Medical Center, New York, New York, USA.
⁹ Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.
¹⁰ National Eye Institute, National Institute of Health, Bethesda, Maryland, USA.
¹¹ Singapore Eye Research Institute, Singapore National Eye Center, Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore.
¹² Tsinghua Medicine, Tsinghua University, Beijing, China.

PMID: 37828734
PMCID: PMC10916935
DOI: 10.1002/alz.13498

Association of fractal dimension and other retinal vascular network parameters with cognitive performance and neuroimaging biomarkers: The Multi-Ethnic Study of Atherosclerosis (MESA)

Sally S Ong et al. Alzheimers Dement. 2024 Feb.

. 2024 Feb;20(2):941-953.

doi: 10.1002/alz.13498. Epub 2023 Oct 12.

Authors

Affiliations

¹ Department of Ophthalmology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
² Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
³ Department of Radiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
⁴ Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
⁵ Department of Psychiatry and Behavioral Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
⁶ Biostatistics and Data Science, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
⁷ Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington, USA.
⁸ Departments of Medicine and Epidemiology, Columbia University Irving Medical Center, New York, New York, USA.
⁹ Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.
¹⁰ National Eye Institute, National Institute of Health, Bethesda, Maryland, USA.
¹¹ Singapore Eye Research Institute, Singapore National Eye Center, Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore.
¹² Tsinghua Medicine, Tsinghua University, Beijing, China.

PMID: 37828734
PMCID: PMC10916935
DOI: 10.1002/alz.13498

Abstract

Introduction: Retinal vascular network changes may reflect the integrity of the cerebral microcirculation, and may be associated with cognitive impairment.

Methods: Associations of retinal vascular measures with cognitive function and MRI biomarkers were examined amongst Multi-Ethnic Study of Atherosclerosis (MESA) participants in North Carolina who had gradable retinal photographs at Exams 2 (2002 to 2004, n = 313) and 5 (2010 to 2012, n = 306), and detailed cognitive testing and MRI at Exam 6 (2016 to 2018).

Results: After adjustment for covariates and multiple comparisons, greater arteriolar fractal dimension (FD) at Exam 2 was associated with less isotropic free water of gray matter regions (β = -0.0005, SE = 0.0024, p = 0.01) at Exam 6, while greater arteriolar FD at Exam 5 was associated with greater gray matter cortical volume (in mm³ , β = 5458, SE = 20.17, p = 0.04) at Exam 6.

Conclusion: Greater arteriolar FD, reflecting greater complexity of the branching pattern of the retinal arteries, is associated with MRI biomarkers indicative of less neuroinflammation and neurodegeneration.

Keywords: Alzheimer's disease; MRI biomarkers; branching angle; curvature tortuosity; dementia; fractal dimension; retinal vascular network parameter.

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Conflict of interest statement

The authors declare that no conflicts of interest exist. Author disclosures are available in the supporting information.

Figures

**FIGURE 1**
Highest (A,C,E) and lowest (B,D,F) quartile representative images of retinal vascular network parameters that were graded using the Singapore “I” Vessel Assessment (SIVA) software. (A,B) Branching angle is calculated from the first angle formed between two daughter vessels of one parent vessel at its bifurcation. (C,D) Curvature tortuosity is derived from the integral of curvature square along the vessel path, normalized by its total path length. (E,F) Fractal dimension is a measurement of the complexity of the whole branching pattern of the retinal vascular tree and is calculated by plotting the logarithm of the number of boxes against the logarithm of the size of the boxes.

**FIGURE 2**
Flow diagram of MESA participants at the Wake Forest Site with retinal imaging, SIVA, brain imaging, and cognitive testing. At MESA Exam 1 (2000 to 2002), 1077 participants were recruited at the Wake Forest site. Of these, 985, 813, and 360 returned for follow up evaluation at Exams 2 (2003 to 2004), 5 (2010 to 2012), and 6 (2016 to 2019), respectively. At Exams 2 and 5, retinal imaging was obtained for 973 and 672 participants, respectively. No retinal imaging was performed at Exam 6. At Exam 6, cognitive testing and adjudication were completed for 320 participants. Of these 320 participants, 317 and 310 also had retinal images taken at Exams 2 and 5, respectively. Brain MRI was performed for 256 participants at Exam 6 and none at Exams 2 and 5. Cognitive testing was also completed for 752 participants at Exam 5 and none at Exam 2. CASI, Cognitive Abilities Screening Instrument; DS, Digit Span; DSC, Digit Symbol Coding; GM, gray matter; MESA, Multi‐Ethnic Study of Atherosclerosis; MRI, magnetic resonance imaging; QC, quality control; SIVA, Singapore I Vessel Assessment; WM, white matter.

See this image and copyright information in PMC

References

1. Corriveau RA, Bosetti F, Emr M, et al. The science of vascular contributions to cognitive impairment and dementia (VCID): a framework for advancing research priorities in the cerebrovascular biology of cognitive decline. Cell Mol Neurobiol. 2016;36(2):281‐288. doi:10.1007/s10571-016-0334-7 - DOI - PMC - PubMed
1. Heringa SM, Bouvy WH, van den Berg E, Moll AC, Kappelle LJ, Biessels GJ. Associations between retinal microvascular changes and dementia, cognitive functioning, and brain imaging abnormalities: a systematic review. J Cereb Blood Flow Metab. 2013;33(7):983‐995. doi:10.1038/jcbfm.2013.58 - DOI - PMC - PubMed
1. Sharrett AR. A review of population‐based retinal studies of the microvascular contribution to cerebrovascular diseases. Ophthalmic Epidemiol. 2007;14(4):238‐242. doi:10.1080/09286580701396712 - DOI - PubMed
1. Ding J, Patton N, Deary IJ, et al. Retinal microvascular abnormalities and cognitive dysfunction: a systematic review. Br J Ophthalmol. 2008;92(8):1017‐1025. doi:10.1136/bjo.2008.141994 - DOI - PubMed
1. Cheung CY, Ong YT, Ikram MK, Chen C, Wong TY. Retinal microvasculature in Alzheimer's disease. J Alzheimers Dis. 2014;42(4):S339‐S352. doi:10.3233/JAD-141596. Suppl. - DOI - PubMed

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Association of fractal dimension and other retinal vascular network parameters with cognitive performance and neuroimaging biomarkers: The Multi-Ethnic Study of Atherosclerosis (MESA)

Affiliations

Association of fractal dimension and other retinal vascular network parameters with cognitive performance and neuroimaging biomarkers: The Multi-Ethnic Study of Atherosclerosis (MESA)

Authors

Affiliations

Abstract

Conflict of interest statement

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