Macular vessel density in the superficial plexus is not associated to cerebrospinal fluid core biomarkers for Alzheimer's disease in individuals with mild cognitive impairment: The NORFACE cohort

Marta Marquié; Ainhoa García-Sánchez; Emilio Alarcón-Martín; Joan Martínez; Miguel Castilla-Martí; Luis Castilla-Martí; Adelina Orellana; Laura Montrreal; Itziar de Rojas; Pablo García-González; Raquel Puerta; Clàudia Olivé; Amanda Cano; Isabel Hernández; Maitée Rosende-Roca; Liliana Vargas; Juan Pablo Tartari; Ester Esteban-De Antonio; Urszula Bojaryn; Mario Ricciardi; Diana M Ariton; Vanesa Pytel; Montserrat Alegret; Gemma Ortega; Ana Espinosa; Alba Pérez-Cordón; Ángela Sanabria; Nathalia Muñoz; Núria Lleonart; Núria Aguilera; Lluís Tárraga; Sergi Valero; Agustín Ruiz; Mercè Boada

doi:10.3389/fnins.2023.1076177

Macular vessel density in the superficial plexus is not associated to cerebrospinal fluid core biomarkers for Alzheimer's disease in individuals with mild cognitive impairment: The NORFACE cohort

Front Neurosci. 2023 Feb 23:17:1076177. doi: 10.3389/fnins.2023.1076177. eCollection 2023.

Authors

Marta Marquié^{1

2}, Ainhoa García-Sánchez¹, Emilio Alarcón-Martín¹, Joan Martínez¹, Miguel Castilla-Martí^{3

4}, Luis Castilla-Martí^{5

6}, Adelina Orellana^{1

2}, Laura Montrreal¹, Itziar de Rojas^{1

2}, Pablo García-González^{1

2}, Raquel Puerta¹, Clàudia Olivé¹, Amanda Cano^{1

2}, Isabel Hernández¹, Maitée Rosende-Roca¹, Liliana Vargas¹, Juan Pablo Tartari¹, Ester Esteban-De Antonio¹, Urszula Bojaryn¹, Mario Ricciardi¹, Diana M Ariton¹, Vanesa Pytel¹, Montserrat Alegret^{1

2}, Gemma Ortega^{1

2}, Ana Espinosa^{1

2}, Alba Pérez-Cordón¹, Ángela Sanabria^{1

2}, Nathalia Muñoz¹, Núria Lleonart¹, Núria Aguilera¹, Lluís Tárraga^{1

2}, Sergi Valero^{1

2}, Agustín Ruiz^{1

2}, Mercè Boada^{1

2}

Affiliations

¹ Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya (UIC), Barcelona, Spain.
² Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
³ Clínica Oftalmológica Dr. Castilla, Barcelona, Spain.
⁴ Vista Alpina Eye Clinic, Visp, Switzerland.
⁵ Ph.D. Programme in Surgery and Morphological Sciences, Universitat Autònoma de Barcelona, Barcelona, Spain.
⁶ Hôpital Ophtalmique Jules-Gonin, Fondation Asile des Aveugles, University of Lausanne, Lausanne, Switzerland.

Abstract

Background: Optical coherence tomography angiography (OCT-A) is a novel method in the dementia field that allows the detection of retinal vascular changes. The comparison of OCT-A measures with established Alzheimer's disease (AD)-related biomarkers is essential to validate the former as a marker of cerebrovascular impairment in the AD continuum. We aimed to investigate the association of macular vessel density (VD) in the superficial plexus quantified by OCT-A with the AT(N) classification based on cerebrospinal fluid (CSF) Aβ1-42, p181-tau and t-tau measurements in individuals with mild cognitive impairment (MCI).

Materials and methods: Clinical, demographic, ophthalmological, OCT-A and CSF core biomarkers for AD data from the Neuro-ophthalmology Research at Fundació ACE (NORFACE) project were analyzed. Differences in macular VD in four quadrants (superior, nasal, inferior, and temporal) among three AT(N) groups [Normal, Alzheimer and Suspected non-Alzheimer pathology (SNAP)] were assessed in a multivariate regression model, adjusted for age, APOE ε4 status, hypertension, diabetes mellitus, dyslipidemia, heart disease, chronic obstructive pulmonary disease and smoking habit, using the Normal AT(N) group as the reference category.

Results: The study cohort comprised 144 MCI participants: 66 Normal AT(N), 45 Alzheimer AT(N) and 33 SNAP AT(N). Regression analysis showed no significant association of the AT(N) groups with any of the regional macular VD measures (all, p > 0.16). The interaction between sex and AT(N) groups had no effect on differentiating VD. Lastly, CSF Aβ1-42, p181-tau and t-tau measures were not correlated to VD (all r < 0.13; p > 0.13).

Discussion: Our study showed that macular VD measures were not associated with the AT(N) classification based on CSF biomarkers in patients with MCI, and did not differ between AD and other underlying causes of cognitive decline in our cohort.

Keywords: AT(N); Alzheimer; NORFACE; cerebrospinal fluid; mild cognitive impairment; optical coherence tomography; vessel density (VD).

Copyright © 2023 Marquié, García-Sánchez, Alarcón-Martín, Martínez, Castilla-Martí, Castilla-Martí, Orellana, Montrreal, de Rojas, García-González, Puerta, Olivé, Cano, Hernández, Rosende-Roca, Vargas, Tartari, Esteban-De Antonio, Bojaryn, Ricciardi, Ariton, Pytel, Alegret, Ortega, Espinosa, Pérez-Cordón, Sanabria, Muñoz, Lleonart, Aguilera, Tárraga, Valero, Ruiz and Boada.

Grants and funding

This project has received funding from the Instituto de Salud Carlos III (ISCIII) Acción Estratégica en Salud, integrated in the Spanish National RCDCI Plan and financed by ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER–Una manera de hacer Europa) grant PI19/00335 awarded to MM, grant PI17/01474 awarded to MB, grants AC17/00100 and PI19/01301 awarded to AR, funded by the European Union Joint Programme–Neurodegenerative Disease Research (JPND) Multinational Research Projects on Personalized Medicine for Neurodegenerative Diseases/Instituto de Salud Carlos III grant AC19/00097 awarded to AR. IR received funding support from the ISCIII grant FI20/00215. AC received funding support from the ISCIII grant Sara Borrell (CD22/00125) and Ministerio de Ciencia e Innovación, Proyectos de Generación de Conocimiento grant PID2021-122473OA-I00. For CSF Biomarker Research, AR and MB received support from the European Union/EFPIA Innovative Medicines Initiative Joint undertaking ADAPTED and MOPEAD projects (grant numbers 115975 and 115985, respectively).