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

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  1   2 , Ainhoa García-Sánchez  1 , Emilio Alarcón-Martín  1 , Joan Martínez  1 , Miguel Castilla-Martí  3   4 , Luis Castilla-Martí  5   6 , Adelina Orellana  1   2 , Laura Montrreal  1 , Itziar de Rojas  1   2 , Pablo García-González  1   2 , Raquel Puerta  1 , Clàudia Olivé  1 , Amanda Cano  1   2 , Isabel Hernández  1 , Maitée Rosende-Roca  1 , Liliana Vargas  1 , Juan Pablo Tartari  1 , Ester Esteban-De Antonio  1 , Urszula Bojaryn  1 , Mario Ricciardi  1 , Diana M Ariton  1 , Vanesa Pytel  1 , Montserrat Alegret  1   2 , Gemma Ortega  1   2 , Ana Espinosa  1   2 , Alba Pérez-Cordón  1 , Ángela Sanabria  1   2 , Nathalia Muñoz  1 , Núria Lleonart  1 , Núria Aguilera  1 , Lluís Tárraga  1   2 , Sergi Valero  1   2 , Agustín Ruiz  1   2 , Mercè Boada  1   2
Affiliations

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 et al. Front Neurosci. .

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).

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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, SA, 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 compensation from these organizations. AR was member of the scientific advisory board of Landsteiner Genmed and Grifols SA. AR holds stocks in Landsteiner Genmed. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Participants’ selection algorithm. AD, Alzheimer’s disease; APOE, apolipoprotein E; OCT-A, optical coherence tomography-angiography; CSF, cerebrospinal fluid; IOP, intraocular pressure; MCI, mild cognitive impairment; SNAP, suspected non-Alzheimer pathology; VD, vessel density.
FIGURE 2
FIGURE 2
Adjusted macular VD measurements by AT(N) group. Macular VD differences among diagnostic groups in (A) nasal, (B) superior, (C) temporal, and (D) inferior quadrants. Macular VD measurements are adjusted by age, APOE ε4 status, hypertension, diabetes mellitus, dyslipidemia, heart disease, COPD and smoking habit. COPD, chronic obstructive pulmonary disease; n.s., non-significant; SNAP, suspected non-Alzheimer pathology; VD, vessel density.
FIGURE 3
FIGURE 3
Representative macular VD images from the superficial vascular plexus for each AT(N) group: Normal (A), Alzheimer (B), and SNAP (C). SNAP, suspected non-Alzheimer pathology; VD, vessel density.
See this image and copyright information in PMC

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