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

García-Sánchez, Ainhoa / Sotolongo-Grau, Oscar / Tartari, Juan Pablo / Sanabria, Ángela / Esteban-De Antonio, Ester / Pérez-Cordón, Alba / Alegret, Montserrat / Pytel, Vanesa / Martínez, Joan / Aguilera, Núria / de Rojas, Itziar / Cano, Amanda / García-González, Pablo / Puerta, Raquel / Olivé, Clàudia / Capdevila, Maria / García-Gutiérrez, Fernando / Vivas, Assumpta / Gómez-Chiari, Marta /

Giménez, Juan / Tejero, Miguel Ángel / Castilla-Martí, Miguel / Castilla-Martí, Luis / Tárraga, Lluís / Valero, Sergi / Ruiz, Agustín / Boada, Mercè / Marquié, Marta

Alzheimer's research & therapy

2024 Volume 16, Issue 1, Page(s) 42

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 ... ...

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.
MeSH term(s)	Humans ; Fluorescein Angiography/methods ; Retinal Vessels/diagnostic imaging ; Retinal Vessels/pathology ; Atrophy/pathology ; Tomography, Optical Coherence/methods
Language	English
Publishing date	2024-02-20
Publishing country	England
Document type	Journal Article
ZDB-ID	2506521-X
ISSN	1758-9193 ; 1758-9193
ISSN (online)	1758-9193
ISSN	1758-9193
DOI	10.1186/s13195-024-01408-9
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Article ; Online: Plasma extracellular vesicles reveal early molecular differences in amyloid positive patients with early-onset mild cognitive impairment.

Cano, Amanda / Esteban-de-Antonio, Ester / Bernuz, Mireia / Puerta, Raquel / García-González, Pablo / de Rojas, Itziar / Olivé, Claudia / Pérez-Cordón, Alba / Montrreal, Laura / Núñez-Llaves, Raúl / Sotolongo-Grau, Óscar / Alarcón-Martín, Emilio / Valero, Sergi / Alegret, Montserrat / Martín, Elvira / Martino-Adami, Pamela V / Ettcheto, Miren / Camins, Antonio / Vivas, Assumpta /

Gomez-Chiari, Marta / Tejero, Miguel Ángel / Orellana, Adelina / Tárraga, Lluís / Marquié, Marta / Ramírez, Alfredo / Martí, Mercè / Pividori, María Isabel / Boada, Mercè / Ruíz, Agustín

Journal of nanobiotechnology

2023 Volume 21, Issue 1, Page(s) 54

Abstract: In the clinical course of Alzheimer's disease (AD) development, the dementia phase is commonly preceded by a prodromal AD phase, which is mainly characterized by reaching the highest levels of Aβ and p-tau-mediated neuronal injury and a mild cognitive ... ...

Abstract	In the clinical course of Alzheimer's disease (AD) development, the dementia phase is commonly preceded by a prodromal AD phase, which is mainly characterized by reaching the highest levels of Aβ and p-tau-mediated neuronal injury and a mild cognitive impairment (MCI) clinical status. Because of that, most AD cases are diagnosed when neuronal damage is already established and irreversible. Therefore, a differential diagnosis of MCI causes in these prodromal stages is one of the greatest challenges for clinicians. Blood biomarkers are emerging as desirable tools for pre-screening purposes, but the current results are still being analyzed and much more data is needed to be implemented in clinical practice. Because of that, plasma extracellular vesicles (pEVs) are gaining popularity as a new source of biomarkers for the early stages of AD development. To identify an exosome proteomics signature linked to prodromal AD, we performed a cross-sectional study in a cohort of early-onset MCI (EOMCI) patients in which 184 biomarkers were measured in pEVs, cerebrospinal fluid (CSF), and plasma samples using multiplex PEA technology of Olink
MeSH term(s)	Humans ; Amyloid beta-Peptides ; Cross-Sectional Studies ; Alzheimer Disease/metabolism ; Cognitive Dysfunction/diagnosis ; tau Proteins/cerebrospinal fluid ; Extracellular Vesicles/metabolism ; Biomarkers ; Peptide Fragments
Chemical Substances	Amyloid beta-Peptides ; tau Proteins ; Biomarkers ; Peptide Fragments
Language	English
Publishing date	2023-02-14
Publishing country	England
Document type	Journal Article
ZDB-ID	2100022-0
ISSN	1477-3155 ; 1477-3155
ISSN (online)	1477-3155
ISSN	1477-3155
DOI	10.1186/s12951-023-01793-7
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Article ; Online: BIOFACE: A Prospective Study of Risk Factors, Cognition, and Biomarkers in a Cohort of Individuals with Early-Onset Mild Cognitive Impairment. Study Rationale and Research Protocols.

Journal of Alzheimer's disease : JAD

2021 Volume 83, Issue 3, Page(s) 1233–1249

Abstract: Background: Mild cognitive impairment (MCI) due to Alzheimer's disease (AD) diagnosis is based on cerebrospinal fluid (CSF) or neuroimaging biomarkers. Currently, non-invasive and inexpensive blood-based biomarkers are being investigated, such as ... ...

Abstract	Background: Mild cognitive impairment (MCI) due to Alzheimer's disease (AD) diagnosis is based on cerebrospinal fluid (CSF) or neuroimaging biomarkers. Currently, non-invasive and inexpensive blood-based biomarkers are being investigated, such as neuronal-derived plasma exosomes (NPEs). Neuroinflammation and early vascular changes have been described in AD pathogenesis and can be traced in plasma and NPEs. However, they have not been studied in early onset MCI (EOMCI). Objective: To describe the rationale, design, and baseline characteristics of the participants from the BIOFACE cohort, a two-year observational study on EOMCI conducted at Fundació ACE. The study goal is to characterize the different phenotypes from a clinical, neuropsychological, and biomarker point of view and to investigate the CSF and plasma proteomics as well as the role of NPEs as early biomarkers of AD. Methods: Participants underwent extended neurological and neuropsychological batteries, multimodal biomarkers including brain MRI, blood, saliva, CSF, anthropometric, and neuro-ophthalmological examinations. Results: Ninety-seven patients with EOMCI were recruited. 59.8%were women. Mean age at symptom onset was 57 years; mean MMSE was 28. First degree and presenile family history of dementia was present in 60.8%and 15.5%, respectively. Depressive and anxiety disorders along with vascular risk factors were the most frequent comorbidities. 29%of participants were APOE ɛ4 carriers, and 67%showed a CSF normal ATN profile. Conclusion: BIOFACE is a two-year study of clinical, cognition, and biomarkers that will shed light on the physiopathology and the potential utility of plasma and NPEs as non-invasive early diagnostic and prognostic biomarkers in people younger than 65 years.
MeSH term(s)	Biomarkers/blood ; Biomarkers/cerebrospinal fluid ; Cognition/physiology ; Cognitive Dysfunction/blood ; Cognitive Dysfunction/diagnosis ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neuropsychological Tests/statistics & numerical data ; Prospective Studies ; Risk Factors
Chemical Substances	Biomarkers
Language	English
Publishing date	2021-08-19
Publishing country	Netherlands
Document type	Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-210254
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Article ; Online: Subtle executive deficits are associated with higher brain amyloid burden and lower cortical volume in subjective cognitive decline: the FACEHBI cohort.

Pérez-Cordón, Alba / Monté-Rubio, Gemma / Sanabria, Angela / Rodriguez-Gomez, Octavio / Valero, Sergi / Abdelnour, Carla / Marquié, Marta / Espinosa, Ana / Ortega, Gemma / Hernandez, Isabel / Rosende-Roca, Maitee / Vargas, Liliana / Mauleón, Ana / Gil, Silvia / Tartari, Juan Pablo / Lomeña, Francisco / Campos, Francisco / Vivas, Assumpta / Gomez-Chiari, Marta /

Benaque, Alba / Ruiz, Agustin / Tárraga, Luis / Boada, Mercè / Alegret, Montserrat

Scientific reports

2020 Volume 10, Issue 1, Page(s) 17721

Abstract: To determine whether lower performance on executive function tests in subjective cognitive decline (SCD) individuals are associated with higher levels of brain amyloid beta (Aβ) deposition and regional volumetric reduction in areas of interest for ... ...

Abstract	To determine whether lower performance on executive function tests in subjective cognitive decline (SCD) individuals are associated with higher levels of brain amyloid beta (Aβ) deposition and regional volumetric reduction in areas of interest for Alzheimer's disease (AD). 195 individuals with SCD from the FACEHBI study were assessed with a neuropsychological battery that included the following nine executive function tests: Trail Making Test A and B (TMTA, TMTB), the Rule Shift Cards subtest of BADS, the Automatic Inhibition subtest of the Syndrom Kurz Test (AI-SKT), Digit Span Backwards and Similarities from WAIS-III, and the letter, semantic, and verb fluency tests. All subjects underwent an 18F-Florbetaben positron emission tomography (FBB-PET) scan to measure global standard uptake value ratio (SUVR), and a magnetic resonance imaging (MRI). A multiple regression analysis, adjusted for age, was carried out to explore the association between global SUVR and performance on executive tests. Then, on those tests significantly associated with amyloid burden, a voxel-based morphometry (VBM) analysis was carried out to explore their correlates with grey matter volume. Multiple regression analysis revealed a statistically significant association between Aβ deposition and performance on one of the executive tests (the AI-SKT). Moreover, VBM analysis showed worse AI-SKT scores were related to lower volume in bilateral hippocampus and left inferior frontal regions. In conclusion, in SCD individuals, worse automatic inhibition ability has been found related to higher cerebral Aβ deposition and lower volume in the hippocampus and frontal regions. Thus, our results may contribute to the early detection of AD in individuals with SCD.
MeSH term(s)	Aged ; Aged, 80 and over ; Alzheimer Disease/diagnosis ; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Amyloid beta-Peptides/metabolism ; Brain/diagnostic imaging ; Brain/metabolism ; Brain/pathology ; Cognitive Dysfunction/diagnosis ; Cognitive Dysfunction/metabolism ; Cognitive Dysfunction/pathology ; Cohort Studies ; Early Diagnosis ; Executive Function/physiology ; Female ; Humans ; Male ; Middle Aged ; Positron Emission Tomography Computed Tomography ; Up-Regulation
Chemical Substances	Amyloid beta-Peptides
Language	English
Publishing date	2020-10-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-74704-7
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Article ; Online: Association between retinal thickness and β-amyloid brain accumulation in individuals with subjective cognitive decline: Fundació ACE Healthy Brain Initiative.

Marquié, Marta / Valero, Sergi / Castilla-Marti, Miguel / Martínez, Joan / Rodríguez-Gómez, Octavio / Sanabria, Ángela / Tartari, Juan Pablo / Monté-Rubio, Gemma C / Sotolongo-Grau, Oscar / Alegret, Montserrat / Pérez-Cordón, Alba / Roberto, Natalia / de Rojas, Itziar / Moreno-Grau, Sonia / Montrreal, Laura / Hernández, Isabel / Rosende-Roca, Maitee / Mauleón, Ana / Vargas, Liliana /

Abdelnour, Carla / Gil, Silvia / Esteban-De Antonio, Ester / Espinosa, Ana / Ortega, Gemma / Lomeña, Francisco / Pavia, Javier / Vivas, Assumpta / Tejero, Miguel Ángel / Gómez-Chiari, Marta / Simó, Rafael / Ciudin, Andreea / Hernández, Cristina / Orellana, Adelina / Benaque, Alba / Ruiz, Agustín / Tárraga, Lluís / Boada, Mercè

Alzheimer's research & therapy

2020 Volume 12, Issue 1, Page(s) 37

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 ... ...

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.
MeSH term(s)	Aged ; Alzheimer Disease/diagnosis ; Amyloid beta-Peptides/metabolism ; Brain/diagnostic imaging ; Brain/metabolism ; Cognitive Dysfunction/diagnostic imaging ; Female ; Humans ; Male ; Middle Aged ; Positron-Emission Tomography ; Retina/diagnostic imaging ; Retina/pathology
Chemical Substances	Amyloid beta-Peptides
Language	English
Publishing date	2020-03-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2506521-X
ISSN	1758-9193 ; 1758-9193
ISSN (online)	1758-9193
ISSN	1758-9193
DOI	10.1186/s13195-020-00602-9
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Article ; Online: Exploring APOE genotype effects on Alzheimer's disease risk and amyloid β burden in individuals with subjective cognitive decline: The FundacioACE Healthy Brain Initiative (FACEHBI) study baseline results.

Moreno-Grau, Sonia / Rodríguez-Gómez, Octavio / Sanabria, Ángela / Pérez-Cordón, Alba / Sánchez-Ruiz, Domingo / Abdelnour, Carla / Valero, Sergi / Hernández, Isabel / Rosende-Roca, Maitée / Mauleón, Ana / Vargas, Liliana / Lafuente, Asunción / Gil, Silvia / Santos-Santos, Miguel Ángel / Alegret, Montserrat / Espinosa, Ana / Ortega, Gemma / Guitart, Marina / Gailhajanet, Anna /

de Rojas, Itziar / Sotolongo-Grau, Óscar / Ruiz, Susana / Aguilera, Nuria / Papasey, Judith / Martín, Elvira / Peleja, Esther / Lomeña, Francisco / Campos, Francisco / Vivas, Assumpta / Gómez-Chiari, Marta / Tejero, Miguel Ángel / Giménez, Joan / Serrano-Ríos, Manuel / Orellana, Adelina / Tárraga, Lluís / Ruiz, Agustín / Boada, Mercè

Alzheimer's & dementia : the journal of the Alzheimer's Association

2017 Volume 14, Issue 5, Page(s) 634–643

Abstract: Introduction: Subjective cognitive decline (SCD) has been proposed as a potential preclinical stage of Alzheimer's disease (AD). Nevertheless, the genetic and biomarker profiles of SCD individuals remain mostly unexplored.: Methods: We evaluated ... ...

Abstract	Introduction: Subjective cognitive decline (SCD) has been proposed as a potential preclinical stage of Alzheimer's disease (AD). Nevertheless, the genetic and biomarker profiles of SCD individuals remain mostly unexplored. Methods: We evaluated apolipoprotein E (APOE) ε4's effect in the risk of presenting SCD, using the Fundacio ACE Healthy Brain Initiative (FACEHBI) SCD cohort and Spanish controls, and performed a meta-analysis addressing the same question. We assessed the relationship between APOE dosage and brain amyloid burden in the FACEHBI SCD and Alzheimer's Disease Neuroimaging Initiative cohorts. Results: Analysis of the FACEHBI cohort and the meta-analysis demonstrated SCD individuals presented higher allelic frequencies of APOE ε4 with respect to controls. APOE dosage explained 9% (FACEHBI cohort) and 11% (FACEHBI and Alzheimer's Disease Neuroimaging Initiative cohorts) of the variance of cerebral amyloid levels. Discussion: The FACEHBI sample presents APOE ε4 enrichment, suggesting that a pool of AD patients is nested in our sample. Cerebral amyloid levels are partially explained by the APOE allele dosage, suggesting that other genetic or epigenetic factors are involved in this AD endophenotype.
MeSH term(s)	Alleles ; Alzheimer Disease/genetics ; Amyloid/blood ; Apolipoprotein E4/genetics ; Biomarkers/metabolism ; Brain/diagnostic imaging ; Brain/metabolism ; Cognitive Dysfunction/diagnostic imaging ; Cognitive Dysfunction/genetics ; Cross-Sectional Studies ; Diagnostic Self Evaluation ; Female ; Genotype ; Humans ; Male ; Meta-Analysis as Topic ; Middle Aged ; Neuroimaging/methods ; Risk Factors ; Spain
Chemical Substances	Amyloid ; Apolipoprotein E4 ; Biomarkers
Language	English
Publishing date	2017-11-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2211627-8
ISSN	1552-5279 ; 1552-5260
ISSN (online)	1552-5279
ISSN	1552-5260
DOI	10.1016/j.jalz.2017.10.005
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Article ; Online: Macular vessel density in the superficial plexus is not a proxy of cerebrovascular damage in non-demented individuals: data from the NORFACE cohort.

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Article ; Online: Plasma extracellular vesicles reveal early molecular differences in amyloid positive patients with early-onset mild cognitive impairment.

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Article ; Online: BIOFACE: A Prospective Study of Risk Factors, Cognition, and Biomarkers in a Cohort of Individuals with Early-Onset Mild Cognitive Impairment. Study Rationale and Research Protocols.

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Article ; Online: Subtle executive deficits are associated with higher brain amyloid burden and lower cortical volume in subjective cognitive decline: the FACEHBI cohort.

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

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Article ; Online: Exploring APOE genotype effects on Alzheimer's disease risk and amyloid β burden in individuals with subjective cognitive decline: The FundacioACE Healthy Brain Initiative (FACEHBI) study baseline results.

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