Association between retinal thickness and β-amyloid brain accumulation in individuals with subjective cognitive decline: Fundació ACE Healthy Brain Initiative

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Abstract

Background

Optical coherence tomography (OCT) of the retina is a fast and easily accessible tool for the quantification of retinal structural measurements. Multiple studies show that patients with Alzheimer’s disease (AD) exhibit thinning in several retinal layers compared to age-matched controls. Subjective cognitive decline (SCD) has been proposed as a risk factor for progression to AD. There is little data about retinal changes in preclinical AD and their correlation with amyloid-β (Aβ) uptake.

Aims

We investigated the association of retinal thickness quantified by OCT with Aβ accumulation and conversion to mild cognitive impairment (MCI) over 24 months in individuals with SCD.

Methods

One hundred twenty-nine individuals with SCD enrolled in Fundació ACE Healthy Brain Initiative underwent comprehensive neuropsychological testing, OCT scan of the retina and florbetaben (FBB) positron emission tomography (PET) at baseline (v0) and after 24 months (v2). We assessed the association of sixteen retinal thickness measurements at baseline with FBB-PET status (+/−) and global standardize uptake value ratio (SUVR) as a continuous measure at v0 and v2 and their predictive value on clinical status change (conversion to mild cognitive impairment (MCI)) at v2.

Results

Mean age of the sample was 64.72 ± 7.27 years; 62.8% were females. Fifteen participants were classified as FBB-PET+ at baseline and 22 at v2. Every 1 μm of increased thickness in the inner nasal macular region conferred 8% and 6% higher probability of presenting a FBB-PET+ status at v0 (OR = 1.08, 95% CI = 1.02–1.14, p = 0.007) and v2 (OR = 1.06, 95% CI = 1.02–1.11, p = 0.004), respectively. Inner nasal macular thickness also positively correlated with global SUVR (at v0: β = 0.23, p = 0.004; at v2: β = 0.26, p = 0.001). No retinal measurements were associated to conversion to MCI over 24 months.

Conclusions

Subtle retinal thickness changes in the macular region are already present in SCD and correlate with Aβ uptake.

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Most cited references 21

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β-Amyloid burden in healthy aging: regional distribution and cognitive consequences.

K Rodrigue, K Kennedy, M D Devous … (2012)

Several lines of evidence suggest that pathologic changes underlying Alzheimer disease (AD) begin years prior to the clinical expression of the disease, underscoring the need for studies of cognitively healthy adults to capture these early changes. The overall goal of the current study was to map the cortical distribution of β-amyloid (Aβ) in a healthy adult lifespan sample (aged 30-89), and to assess the relationship between elevated amyloid and cognitive performance across multiple domains. A total of 137 well-screened and cognitively normal adults underwent Aβ PET imaging with radiotracer (18)F-florbetapir. Aβ load was estimated from 8 cortical regions. Participants were genotyped for APOE and tested for processing speed, working memory, fluid reasoning, episodic memory, and verbal ability. Aβ deposition is distributed differentially across the cortex and progresses at varying rates with age across cortical brain regions. A subset of cognitively normal adults aged 60 and over show markedly elevated deposition, and also had a higher rate of APOE ε4 (38%) than nonelevated adults (19%). Aβ burden was linked to poorer cognitive performance on measures of processing speed, working memory, and reasoning. Even in a highly selected lifespan sample of adults, Aβ deposition is apparent in some adults and is influenced by APOE status. Greater amyloid burden was related to deleterious effects on cognition, suggesting that subtle cognitive changes accrue as amyloid progresses.

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The inner blood-retinal barrier: Cellular basis and development

Mónica Díaz-Coránguez, Carla Ramos, David A Antonetti (2017)

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Automated layer segmentation of macular OCT images using dual-scale gradient information.

Makoto Araie, Zhenguo Wang, Kinpui Chan … (2010)

A novel automated boundary segmentation algorithm is proposed for fast and reliable quantification of nine intra-retinal boundaries in optical coherence tomography (OCT) images. The algorithm employs a two-step segmentation schema based on gradient information in dual scales, utilizing local and complementary global gradient information simultaneously. A shortest path search is applied to optimize the edge selection. The segmentation algorithm was validated with independent manual segmentation and a reproducibility study. It demonstrates high accuracy and reproducibility in segmenting normal 3D OCT volumes. The execution time is about 16 seconds per volume (480x512x128 voxels). The algorithm shows potential for quantifying images from diseased retinas as well.

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Author and article information

Contributors

Marta Marquié: mmarquie@fundacioace.org

Journal

Journal ID (nlm-ta): Alzheimers Res Ther

Journal ID (iso-abbrev): Alzheimers Res Ther

Title: Alzheimer's Research & Therapy

Publisher: BioMed Central (London )

ISSN (Electronic): 1758-9193

Publication date (Electronic): 31 March 2020

Publication date PMC-release: 31 March 2020

Publication date Collection: 2020

Volume: 12

Electronic Location Identifier: 37

Affiliations

[1 ]GRID grid.410675.1, ISNI 0000 0001 2325 3084, Research Center and Memory Clinic, , Fundació ACE Institut Català de Neurociències Aplicades - Universitat Internacional de Catalunya (UIC), ; Gran Via Carles III, 85 bis, 08028 Barcelona, Spain

[2 ]GRID grid.413448.e, ISNI 0000 0000 9314 1427, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), , Instituto de Salud Carlos III, ; Madrid, Spain

[3 ]Clínica Oftalmológica Dr. Castilla, Barcelona, Spain

[4 ]GRID grid.411142.3, ISNI 0000 0004 1767 8811, Department of Ophthalmology, , Hospital del Mar and Hospital de l’Esperança - Parc de Salut Mar, ; Barcelona, Spain

[5 ]GRID grid.5841.8, ISNI 0000 0004 1937 0247, Department of Radiology, Hospital Clínic i Provincial de Barcelona, , Universitat de Barcelona, ; Barcelona, Spain

[6 ]Department of Diagnostic Imaging, Clínica Corachan, Barcelona, Spain

[7 ]GRID grid.413448.e, ISNI 0000 0000 9314 1427, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), , Instituto de Salud Carlos III, ; Madrid, Spain

[8 ]GRID grid.7080.f, Institut de Recerca Vall d’Hebron, , Universitat Autònoma de Barcelona (VHIR-UAB), ; Barcelona, Spain

Article

Publisher ID: 602

DOI: 10.1186/s13195-020-00602-9

PMC ID: 7110730

PubMed ID: 32234080

SO-VID: b048a027-5475-4097-93a8-553eab5a404c

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 13 August 2019

Date accepted : 20 March 2020

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100010665, H2020 Marie Skłodowska-Curie Actions;

Award ID: 796706

Award Recipient : Marta Marquié

Funded by: European Foundation for the Study of Diabetes - ESFS/Lilly Mental Health and Diabetes 2013 Programme

Funded by: Grifols

Funded by: Life Molecular Imaging

Award ID: N/A

Funded by: Araclon Biotech

Award ID: N/A

Funded by: Fundació ACE Institut Català de Neurociències Aplicades

Award ID: N/A

Funded by: Alkahest

Award ID: N/A

Funded by: Laboratorio de análisis Echevarne

Award ID: N/A

Funded by: IrsiCaixa

Award ID: N/A

Custom metadata

ScienceOpen disciplines: Neurology

Keywords: optical coherence tomography,retinal thickness,subjective cognitive decline,β-amyloid,florbetaben,positron emission tomography

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ScienceOpen disciplines: Neurology

Keywords: optical coherence tomography, retinal thickness, subjective cognitive decline, β-amyloid, florbetaben, positron emission tomography

Association between retinal thickness and β-amyloid brain accumulation in individuals with subjective cognitive decline: Fundació ACE Healthy Brain Initiative

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Nanoparticles to cross the blood-brain barrier (BBB)

Most cited references 21

β-Amyloid burden in healthy aging: regional distribution and cognitive consequences.

The inner blood-retinal barrier: Cellular basis and development

Automated layer segmentation of macular OCT images using dual-scale gradient information.

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