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. 2024 Feb 20;16(1):42.
doi: 10.1186/s13195-024-01408-9.

Macular vessel density in the superficial plexus is not a proxy of cerebrovascular damage in non-demented individuals: data from the NORFACE cohort

Ainhoa García-Sánchez  1 , Oscar Sotolongo-Grau  1 , Juan Pablo Tartari  1 , Ángela Sanabria  1   2 , Ester Esteban-De Antonio  1 , Alba Pérez-Cordón  1 , Montserrat Alegret  1   2 , Vanesa Pytel  1 , Joan Martínez  1 , Núria Aguilera  1 , Itziar de Rojas  1   2 , Amanda Cano  1   2 , Pablo García-González  1 , Raquel Puerta  1 , Clàudia Olivé  1 , Maria Capdevila  1 , Fernando García-Gutiérrez  1 , Assumpta Vivas  3 , Marta Gómez-Chiari  3 , Juan Giménez  3 , Miguel Ángel Tejero  3 , Miguel Castilla-Martí  4   5 , Luis Castilla-Martí  6   7 , Lluís Tárraga  1   2 , Sergi Valero  1   2 , Agustín Ruiz  1   2 , Mercè Boada  1   2 , Marta Marquié  8   9 ; FACEHBI study group; BIOFACE study group
Collaborators, Affiliations

Macular vessel density in the superficial plexus is not a proxy of cerebrovascular damage in non-demented individuals: data from the NORFACE cohort

Ainhoa García-Sánchez et al. Alzheimers Res Ther. .

Abstract

Introduction: Optical coherence tomography angiography (OCT-A) is a novel tool that allows the detection of retinal vascular changes. We investigated the association of macular vessel density (VD) in the superficial plexus assessed by OCT-A with measures of cerebrovascular pathology and atrophy quantified by brain magnetic resonance imaging (MRI) in non-demented individuals.

Methods: Clinical, demographical, OCT-A, and brain MRI data from non-demented research participants were included. We analyzed the association of regional macular VD with brain vascular burden using the Fazekas scale assessed in a logistic regression analysis, and the volume of white matter hyperintensities (WMH) assessed in a multiple linear regression analysis. We also explored the associations of macular VD with hippocampal volume, ventricle volume and Alzheimer disease cortical signature (ADCS) thickness assessed in multiple linear regression analyses. All analyses were adjusted for age, sex, syndromic diagnosis and cardiovascular variables.

Results: The study cohort comprised 188 participants: 89 with subjective cognitive decline and 99 with mild cognitive impairment. No significant association of regional macular VD with the Fazekas categories (all, p > 0.111) and WMH volume (all, p > 0.051) were detected. VD in the nasal quadrant was associated to hippocampal volume (p = 0.007), but no other associations of macular VD with brain atrophy measures were detected (all, p > 0.05).

Discussion: Retinal vascular measures were not a proxy of cerebrovascular damage in non-demented individuals, while VD in the nasal quadrant was associated with hippocampal atrophy independently of the amyloid status.

Keywords: BIOFACE; Brain atrophy; Cerebrovascular damage; FACEHBI; NORFACE; Optical coherence tomography-angiography; Vessel density.

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Conflict of interest statement

MB has consulted for Araclon, Avid, Grifols, Lilly, Nutricia, Roche, Eisai and Servier. She received fees from lectures and funds for research from Araclon, Biogen, Grifols, Nutricia, Roche and Servier. She reports grants/research funding from Abbvie, Araclon, Biogen Research Limited, Bioiberica, Grifols, Lilly, S.A, Merck Sharp & Dohme, Kyowa Hakko Kirin, Laboratorios Servier, Nutricia SRL, Oryzon Genomics, Piramal Imaging Limited, Roche Pharma SA, and Schwabe Farma Iberica SLU, all outside the submitted work. She has not received personal compensations from these organizations. AR is member of scientific advisory board of Landsteiner Genmed and Grifols SA. AR has stocks of Landsteiner Genmed. MM has consulted for F. Hoffmann-La Roche Ltd. The rest of authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Representative MRI T2-weighted images from a 68-year-old male with SCD showing A substantial WMH damage (Fazekas scale score = 3) and B isolation and masking of the WMH burden (in red) using the PGS software. Abbreviations: MRI: magnetic resonance imaging; WMH: white matter hyperintensitiy; SCD: subjective cognitive decline
Fig. 2
Fig. 2
Study flowchart. Abbreviations: APOE: apolipoprotein E; CSF: cerebrospinal fluid; IOP: intraocular pressure; MCI: mild cognitive impairment; MRI: magnetic brain imaging; OCT-A: Optical Coherence Tomography – angiography; PET: positron emission tomography; SCD: subjective cognitive decline
Fig. 3
Fig. 3
Representative OCT-A and brain MRI images from the study participants. A 68-year-old female with SCD and high CV damage (Fazekas scale score = 2, WMH volume = 30,943 mm3). B 61-year-old female with MCI and high CV damage (Fazekas scale score = 3, WMH volume = 27,000 mm3). C 61-year-old female with SCD and low CV damage (Fazekas scale score = 0, WMH volume = 290 mm3). D 60-year-old female with MCI and low CV damage (Fazekas scale score = 0, WMH volume = 710 mm3). Abbreviations: CV: cerebrovascular; MCI: mild cognitive impairment; MRI: magnetic ressonance imaging; OCT-A: Optical Coherence Tomography – angiography; SCD: subjective cognitive decline; WMH: white matter hyperintensity
Fig. 4
Fig. 4
Adjusted macular VD measurements by Fazekas categories. Macular VD differences between Fazekas categories in A nasal, B superior, C temporal, and D inferior quadrants. Macular VD measures are adjusted by age, sex, syndromic diagnosis, hypertension, diabetes mellitus, dyslipidemia, heart disease, respiratory disease, and smoking. Abbreviations: n.s.: non-significant; VD: vessel density
Fig. 5
Fig. 5
Association of macular VD and WMH volume. Association of macular VD in A nasal, B superior, C temporal, and D inferior quadrants with WHM volume. Macular VD measures are adjusted by age, sex, syndromic diagnosis, hypertension, diabetes mellitus, dyslipidemia, heart disease, respiratory disease, and smoking. Abbreviations: n.s.: non-significant; VD: vessel density; WMH: white matter hyperintensity
Fig. 6
Fig. 6
Association of macular VD and hippocampal volume. Association of macular VD in A nasal, B superior, C temporal, and D inferior quadrants with hippocampal volume. Macular VD measures are adjusted by age, sex, syndromic diagnosis, hypertension, diabetes mellitus, dyslipidemia, heart disease, respiratory disease, and smoking. Abbreviations: n.s.: non-significant; VD: vessel density; WMH: white matter hyperintensity
Fig. 7
Fig. 7
Association of macular VD and ventricle volume. Association of macular VD in A nasal, B superior, C temporal, and D inferior quadrants with ventricle volume. Macular VD measures are adjusted by age, sex, syndromic diagnosis, hypertension, diabetes mellitus, dyslipidemia, heart disease, respiratory disease, and smoking. Abbreviations: n.s.: non-significant; VD: vessel density
Fig. 8
Fig. 8
Association of macular VD and ADCS thickness. Association of macular VD in A nasal, B superior, C temporal, and D inferior quadrants with ACDS thickness. Macular VD measures are adjusted by age, sex, syndromic diagnosis, hypertension, diabetes mellitus, dyslipidemia, heart disease, respiratory disease, and smoking. Abbreviations: ADCS: Alzheimer’s disease cortical signature; non-significant; VD: vessel density
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