17 results on '"Esteban-De Antonio, Ester"'
Search Results
2. Plasma extracellular vesicles reveal early molecular differences in amyloid positive patients with early-onset mild cognitive impairment
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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, and Ruíz, Agustín
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- 2023
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3. Differences in macular vessel density in the superficial plexus across cognitive impairment: the NORFACE cohort
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Marquié, Marta, Valero, Sergi, Martínez, Joan, Alarcón-Martín, Emilio, García-Sánchez, Ainhoa, de Rojas, Itziar, Castilla-Martí, Miguel, Castilla-Martí, Luis, Hernández, Isabel, Rosende-Roca, Maitée, Vargas, Liliana, Tartari, Juan Pablo, Esteban-De Antonio, Ester, Bojaryn, Urszula, Pytel, Vanesa, Narvaiza, Leire, Alegret, Montserrat, Ortega, Gemma, Espinosa, Ana, Sanabria, Ángela, Pérez-Cordón, Alba, Lleonart, Núria, Muñoz, Nathalia, Tárraga, Lluís, Ruiz, Agustín, and Boada, Mercè
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- 2022
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4. Interaction of neuropsychiatric symptoms with APOE ε4 and conversion to dementia in MCI patients in a Memory Clinic
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Valero, Sergi, Marquié, Marta, De Rojas, Itziar, Espinosa, Ana, Moreno-Grau, Sonia, Orellana, Adelina, Montrreal, Laura, Hernández, Isabel, Mauleón, Ana, Rosende-Roca, Maitée, Alegret, Montse, Pérez-Cordón, Alba, Ortega, Gemma, Roberto, Natalia, Sanabria, Angela, Abdelnour, Carla, Gil, Silvia, Tartari, Juan Pablo, Vargas, Liliana, Esteban-De Antonio, Ester, Benaque, Alba, Tárraga, Lluís, Boada, Mercè, and Ruíz, Agustín
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- 2020
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5. Extracellular vesicles, the emerging mirrors of brain physiopathology.
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Cano, Amanda, Ettcheto, Miren, Bernuz, Mireia, Puerta, Raquel, Esteban de Antonio, Ester, Sánchez-López, Elena, Souto, Eliana B., Camins, Antonio, Martí, Mercè, Isabel Pividori, María, Boada, Mercè, and Ruiz, Agustín
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- 2023
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6. The Synergic Effect of AT(N) Profiles and Depression on the Risk of Conversion to Dementia in Patients with Mild Cognitive Impairment.
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Marquié, Marta, García-Gutiérrez, Fernando, Orellana, Adelina, Montrreal, Laura, de Rojas, Itziar, García-González, Pablo, Puerta, Raquel, Olivé, Clàudia, Cano, Amanda, Hernández, Isabel, Rosende-Roca, Maitée, Vargas, Liliana, Tartari, Juan Pablo, Esteban-De Antonio, Ester, Bojaryn, Urszula, Ricciardi, Mario, Ariton, Diana M., Pytel, Vanesa, Alegret, Montserrat, and Ortega, Gemma
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MILD cognitive impairment ,DISEASE risk factors ,DEMENTIA patients ,ALZHEIMER'S disease ,MENTAL depression ,CEREBROSPINAL fluid - Abstract
Few studies have addressed the impact of the association between Alzheimer's disease (AD) biomarkers and NPSs in the conversion to dementia in patients with mild cognitive impairment (MCI), and no studies have been conducted on the interaction effect of these two risk factors. AT(N) profiles were created using AD-core biomarkers quantified in cerebrospinal fluid (CSF) (normal, brain amyloidosis, suspected non-Alzheimer pathology (SNAP) and prodromal AD). NPSs were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q). A total of 500 individuals with MCI were followed-up yearly in a memory unit. Cox regression analysis was used to determine risk of conversion, considering additive and multiplicative interactions between AT(N) profile and NPSs on the conversion to dementia. A total of 224 participants (44.8%) converted to dementia during the 2-year follow-up study. Pathologic AT(N) groups (brain amyloidosis, prodromal AD and SNAP) and the presence of depression and apathy were associated with a higher risk of conversion to dementia. The additive combination of the AT(N) profile with depression exacerbates the risk of conversion to dementia. A synergic effect of prodromal AD profile with depressive symptoms is evidenced, identifying the most exposed individuals to conversion among MCI patients. [ABSTRACT FROM AUTHOR]
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- 2023
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7. Establishing In-House Cutoffs of CSF Alzheimer's Disease Biomarkers for the AT(N) Stratification of the Alzheimer Center Barcelona Cohort.
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Orellana, Adelina, García-González, Pablo, Valero, Sergi, Montrreal, Laura, de Rojas, Itziar, Hernández, Isabel, Rosende-Roca, Maitee, Vargas, Liliana, Tartari, Juan Pablo, Esteban-De Antonio, Ester, Bojaryn, Urszula, Narvaiza, Leire, Alarcón-Martín, Emilio, Alegret, Montserrat, Alcolea, Daniel, Lleó, Alberto, Tárraga, Lluís, Pytel, Vanesa, Cano, Amanda, and Marquié, Marta
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ALZHEIMER'S disease ,CEREBROSPINAL fluid examination ,BLAND-Altman plot ,CEREBROSPINAL fluid ,POSITRON emission tomography ,MILD cognitive impairment ,ENZYME-linked immunosorbent assay ,CHEMILUMINESCENCE immunoassay - Abstract
Background: Clinical diagnosis of Alzheimer's disease (AD) increasingly incorporates CSF biomarkers. However, due to the intrinsic variability of the immunodetection techniques used to measure these biomarkers, establishing in-house cutoffs defining the positivity/negativity of CSF biomarkers is recommended. However, the cutoffs currently published are usually reported by using cross-sectional datasets, not providing evidence about its intrinsic prognostic value when applied to real-world memory clinic cases. Methods: We quantified CSF Aβ1-42, Aβ1-40, t-Tau, and p181Tau with standard INNOTEST
® ELISA and Lumipulse G® chemiluminescence enzyme immunoassay (CLEIA) performed on the automated Lumipulse G600II. Determination of cutoffs included patients clinically diagnosed with probable Alzheimer's disease (AD, n = 37) and subjective cognitive decline subjects (SCD, n = 45), cognitively stable for 3 years and with no evidence of brain amyloidosis in 18F-Florbetaben-labeled positron emission tomography (FBB-PET). To compare both methods, a subset of samples for Aβ1-42 (n = 519), t-Tau (n = 399), p181Tau (n = 77), and Aβ1-40 (n = 44) was analyzed. Kappa agreement of single biomarkers and Aβ1-42/Aβ1-40 was evaluated in an independent group of mild cognitive impairment (MCI) and dementia patients (n = 68). Next, established cutoffs were applied to a large real-world cohort of MCI subjects with follow-up data available (n = 647). Results: Cutoff values of Aβ1-42 and t-Tau were higher for CLEIA than for ELISA and similar for p181Tau. Spearman coefficients ranged between 0.81 for Aβ1-40 and 0.96 for p181TAU. Passing–Bablok analysis showed a systematic and proportional difference for all biomarkers but only systematic for Aβ1-40. Bland–Altman analysis showed an average difference between methods in favor of CLEIA. Kappa agreement for single biomarkers was good but lower for the Aβ1-42/Aβ1-40 ratio. Using the calculated cutoffs, we were able to stratify MCI subjects into four AT(N) categories. Kaplan–Meier analyses of AT(N) categories demonstrated gradual and differential dementia conversion rates (p = 9.815−27 ). Multivariate Cox proportional hazard models corroborated these findings, demonstrating that the proposed AT(N) classifier has prognostic value. AT(N) categories are only modestly influenced by other known factors associated with disease progression. Conclusions: We established CLEIA and ELISA internal cutoffs to discriminate AD patients from amyloid-negative SCD individuals. The results obtained by both methods are not interchangeable but show good agreement. CLEIA is a good and faster alternative to manual ELISA for providing AT(N) classification of our patients. AT(N) categories have an impact on disease progression. AT(N) classifiers increase the certainty of the MCI prognosis, which can be instrumental in managing real-world MCI subjects. [ABSTRACT FROM AUTHOR]- Published
- 2022
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8. Cerebral amyloid angiopathy-related transient focal neurological episodes: A transient ischemic attack mimic with an increased risk of intracranial hemorrhage
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Vales-Montero, Marta, García-Pastor, Andrés, Iglesias-Mohedano, Ana María, Esteban-de Antonio, Ester, Salgado-Cámara, Paula, García-Domínguez, José Manuel, Vázquez-Alén, Pilar, Díaz-Otero, Fernando, Fernández-Bullido, Yolanda, and Gil-Núñez, Antonio
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- 2019
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9. Neuropsychiatric Profile as a Predictor of Cognitive Decline in Mild Cognitive Impairment.
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Roberto, Natalia, Portella, Maria J., Marquié, Marta, Alegret, Montserrat, Hernández, Isabel, Mauleón, Ana, Rosende-Roca, Maitee, Abdelnour, Carla, Esteban de Antonio, Ester, Tartari, Juan P., Vargas, Liliana, López-Cuevas, Rogelio, Bojaryn, Urszula, Espinosa, Ana, Ortega, Gemma, Pérez-Cordón, Alba, Sanabria, Ángela, Orellana, Adelina, de Rojas, Itziar, and Moreno-Grau, Sonia
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COGNITION disorders ,MILD cognitive impairment ,VERBAL learning ,PROGNOSIS ,COGNITIVE ability ,SYMPTOMS - Abstract
Introduction: Mild cognitive impairment is often associated with affective and other neuropsychiatric symptoms (NPS). This co-occurrence might have a relevant impact on disease progression, from MCI to dementia. Objective: The aim of this study was to explore the trajectories of cognitive decline in an MCI sample from a memory clinic, taking into consideration a perspective of isolated cognitive functions and based on NPS clusters, accounting for the different comorbid symptoms collected at their baseline visit. Methods: A total of 2,137 MCI patients were monitored over a 2.4-year period. Four clusters of NPS (i.e., Irritability, Apathy, Anxiety/Depression and Asymptomatic) were used to run linear mixed models to explore the interaction of cluster with time on cognitive trajectories using a comprehensive neuropsychological battery (NBACE) administered at baseline and at the three subsequent follow-ups. Results: A significant interaction between cluster and time in cognitive decline was found when verbal learning and cued-recall were explored (p = 0.002 for both memory functions). For verbal learning, the Irritability cluster had the largest effect size (0.69), whereas the Asymptomatic cluster showed the smallest effect size (0.22). For cued-recall, the Irritability cluster had the largest effect size among groups (0.64), and Anxiety/Depression had the smallest effect size (0.21). Conclusions: In MCI patients, the Irritability and Apathy NPS clusters shared similar patterns of worsening in memory functioning, which could point to these NPS as risk factors of a faster cognitive decline, acting as early prognostic markers and helping in the diagnostic process. [ABSTRACT FROM AUTHOR]
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- 2021
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10. Macular vessel density in the superficial plexus is not associated to cerebrovascular damage in non‐demented individuals: data from the NORFACE cohort.
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Marquié, Marta, García‐Sánchez, Ainhoa, Sotolongo‐Grau, Oscar, Tartari, Juan Pablo, Sanabria, Angela, Esteban‐De Antonio, Ester, Pérez, Alba, Castilla‐Martí, Miguel, Castilla‐Martí, Luis, Martínez, Joan, Alarcón‐Martín, Emilio, Alegret, Montserrat, Aguilera, Núria, Vivas, Assumpta, M, Gómez‐Chiari, Escudero, José Miguel, Tejero, Miguel Angel, Tárraga, Lluís, Ruiz, Agustin, and Boada, Mercè
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Background: Optical Coherence Tomography angiography (OCT‐A) is a novel tool that allows the detection of retinal vascular changes. The comparison of OCT‐A measures with brain vascular burden is essential to validate the former as a surrogate of cerebrovascular damage and biomarker of cognitive decline. We aimed to investigate the association of macular vessel density (VD) in the superficial plexus assessed by OCT‐A with measures of cerebrovascular pathology quantified by brain magnetic resonance imaging (MRI) in a cohort of non‐demented individuals. Method: Clinical, demographical, APOE ε4 status, amyloid status, OCT‐A and brain MRI data from non‐demented participants of the FACEHBI and BIOFACE studies were included. We analyzed the association of macular VD in four quadrants (superior, nasal, inferior and temporal) with brain vascular burden using the Fazekas scale scores (dichotomized in two categories, 0‐1 vs 2‐3), assessed in a logistic regression analysis, and the volume of white matter hyperintensities (WMH) quantified by Freesurfer assessed in a multiple regression analysis. We additionally explored the associations of macular VD with hippocampal volume, ventricles volume and Alzheimer Disease cortical signature (ADCS) thickness assessed in a multiple regression analysis. All analyses were adjusted for age and dyslipidemia. Result: The study cohort comprised 188 participants: 89 with subjective cognitive decline (SCD) and 99 with mild cognitive impairment (MCI). Logistic regression analysis showed no significant differences of regional macular VD between the two Fazekas groups (all, p>0.05). Multiple regression analysis showed no significant association of regional macular VD with the volume of WMH (all, p>0.05). Macular VD in the nasal and inferior quadrants were positively associated with hippocampal volume (p = 0.009 and p = 0.021, respectively), but no association was detected with ventricles volume or ADCS thickness (both p>0.05). Conclusion: Our study showed that retinal vascular measures (regional macular VD in the superficial vascular plexus) assessed by OCT‐A were not associated with brain vascular damage quantified by the Fazekas scale and the WMH burden n in a cohort of non‐demented research participants with SCD and MCI. [ABSTRACT FROM AUTHOR]
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- 2023
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11. 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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Esteban de Antonio, Ester, Pérez-Cordón, Alba, Gil, Silvia, Orellana, Adelina, Cano, Amanda, Alegret, Montserrat, Espinosa, Ana, Alarcón-Martín, Emilio, Valero, Sergi, Martínez, Joan, de Rojas, Itziar, Sotolongo-Grau, Óscar, Martín, Elvira, Vivas, Assumpta, Gomez-Chiari, Marta, Tejero, Miguel Ángel, Bernuz, Mireia, Tárraga, Lluis, Ruiz, Agustín, and Marquié, Marta
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MILD cognitive impairment , *PROGNOSIS , *ALZHEIMER'S disease , *LONGITUDINAL method , *BIOMARKERS , *RESEARCH , *RESEARCH methodology , *COGNITION , *MAGNETIC resonance imaging , *MEDICAL cooperation , *EVALUATION research , *NEUROPSYCHOLOGICAL tests , *COMPARATIVE studies , *PSYCHOLOGICAL tests - 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. [ABSTRACT FROM AUTHOR]- Published
- 2021
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12. Pathological Correlations of Neuropsychiatric Symptoms in Institutionalized People with Dementia.
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Esteban de Antonio, Ester, López-Álvarez, Jorge, Rábano, Alberto, Agüera-Ortiz, Luis, Sánchez-Soblechero, Antonio, Amaya, Laura, Portela, Sofía, Cátedra, Carlos, Olazarán, Javier, and de Antonio, Ester Esteban
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APATHY , *SYMPTOMS , *DEMENTIA , *ALZHEIMER'S disease , *SENILE dementia , *OLDER people , *SLEEP disorders - Abstract
Background: Comprehensive clinicopathological studies of neuropsychiatric symptoms (NPS) in dementia are lacking.Objective: To describe the pathological correlations of NPS in a sample of institutionalized people with dementia.Methods: We studied 59 people who were consecutively admitted to a nursing home and donated their brain. Correlations between pathological variables and NPS upon admission (n = 59) and at one-year follow-up assessment (n = 46) were explored and confirmed using bivariate and multivariate statistical methods.Results: Mean (SD) age at admission was 83.2 (6.4) years and mean (SD) age at demise was 85.4 (6.6); 73% of the subjects were female and 98% presented advanced dementia. The most frequent etiological diagnosis was Alzheimer's disease (AD; 74.6% clinical diagnosis, 67.8% pathological diagnosis). The pathological diagnosis of AD was associated with aggression (β est 0.31), depression (β est 0.31), anxiety (β est 0.38), and irritability (β est 0.28). Tau stage correlated with aggressive symptoms (β est 0.32) and anxiety (βest 0.33). Coexistence of AD and Lewy body pathology was associated with depression (β est 0.32), while argyrophilic grains were associated with eating symptoms (β est 0.29). Predictive models were achieved for apathy, including cognitive performance, basal ganglia ischemic lesions, and sex as predictors (R2 0.38) and for sleep disorders, including pathological diagnosis of AD and age at demise (R2 0.18) (all p-values <0.05, unadjusted).Conclusion: AD was the main pathological substrate of NPS in our sample of very elderly people with advanced dementia. However, correlations were mild, supporting a model of focal/asymmetric rather than diffuse brain damage, along with relevance of environmental and other personal factors, in the genesis of those symptoms. [ABSTRACT FROM AUTHOR]- Published
- 2020
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13. Managing Clinical Trials for Alzheimer's Disease During the COVID-19 Crisis: Experience at Fundació ACE in Barcelona, Spain.
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Abdelnour, Carla, Esteban de Antonio, Ester, Pérez-Cordón, Alba, Lafuente, Asunción, Buendía, Mar, Pancho, Ana, Jofresa, Sara, Aguilera, Nuria, Ibarria, Marta, Cuevas, Rosario, Cañada, Laia, Calvet, Anna, Diego, Susana, González-Pérez, Antonio, Orellana, Adela, Montrreal, Laura, de Jorge, Laura, Marquié, Marta, Benaque, Alba, and Gurruchaga, Miren
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COVID-19 pandemic , *ALZHEIMER'S disease , *CLINICAL trials , *SERODIAGNOSIS , *SARS-CoV-2 , *ALZHEIMER'S disease treatment , *PREVENTION of epidemics , *VIRAL pneumonia , *EXPERIMENTAL design , *CLINICAL pathology , *COVID-19 , *MEDICAL care , *PATIENTS , *CLINICS , *TELEMEDICINE - Abstract
Background: The COVID-19 pandemic has brought great disruption to health systems worldwide. This affected ongoing clinical research, particularly among those most vulnerable to the pandemic, like dementia patients. Fundació ACE is a research center and memory clinic based in Barcelona, Spain, one of the hardest-hit countries.Objective: To describe the ad-hoc strategic plan developed to cope with this crisis and to share its outcomes.Methods: We describe participants' clinical and demographic features. Additionally, we explain our strategic plan aimed at minimizing the impact on clinical trial research activities, which included SARS-CoV-2 RT-PCR and IgG serological tests to all participants and personnel. The outcomes of the plan are described in terms of observed safety events and drop-outs during the study period.Results: A total of 130 patients were participating in 16 active clinical trials in Fundació ACE when the lockdown was established. During the confinement, we performed 1018 calls to the participants, which led to identify adverse events in 26 and COVID-19 symptoms in 6. A total of 83 patients (64%) could restart on-site visits as early as May 11, 2020. All SARS-CoV-2 RT-PCR diagnostic tests performed before on-site visits were negative and only three IgG serological tests were positive. Throughout the study period, we only observed one drop-out, due to an adverse event unrelated to COVID-19.Discussion: The plan implemented by Fundació ACE was able to preserve safety and integrity of ongoing clinical trials. We must use the lessons learned from the pandemic and design crisis-proof protocols for clinical trials. [ABSTRACT FROM AUTHOR]- Published
- 2020
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14. Comparison of automated CLEIA and manual ELISA immunoassays for CSF AD biomarkers: The Fundació ACE Biomarker Research Program (FACEBREP).
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Orellana, Adelina, Valero, Sergi, Abdelnour, Carla, Montrreal, Laura, de Rojas, Itziar, Rosende‐Roca, Maitee, Mauleon, Ana, Vargas, Liliana, Tartari, Juan Pablo, Esteban‐De Antonio, Ester, García‐González, Pablo, Alarcón‐Martín, Emilio, Alegret, Montserrat, Alcolea, Daniel, Lleó, Alberto, Hernandez, Isabel, Tarraga, Lluis, Marquié, Marta, and Boada, Mercè
- Abstract
Background: Clinical diagnosis of Alzheimer's disease (AD) increasingly incorporate CSF biomarkers. However due to the intrinsic variability of the immunodetection techniques used to measure these biomarkers, it is recommended to establish in‐house cutoffs defining the positivity/negativity of CSF biomarkers. Method: We quantified CSF Aβ1‐42, t‐Tau, p181Tau and Aβ1‐40 with standard INNOTEST® ELISA and Lumipulse G® chemiluminescence enzyme‐immunoassay (CLEIA) performed on automated Lumipulse G600II. Determination of cutoffs included patients clinically diagnosed with Alzheimer Disease (AD, n=37) and amyloid‐negative Subjective Cognitive Decline subjects (SCD, n=45), cognitively stable during 3‐years and with no evidence of brain amyloidosis in 18F‐Florbetaben‐labeled positron emission tomography (FBB‐PET). To compare both methods, a subset of samples for Aβ1‐42 (n=519), t‐Tau (n=399), p181Tau (n=77) and Aβ1‐40 (n=44) were analyzed. Kappa agreement of single biomarkers and Aβ1‐42/Aβ1‐40 was performed in an independent group of mild cognitive impairment (MCI) and dementia patients (n=68). Result: Cutoffs values of Aβ1‐42 and t‐Tau were higher for CLEIA than for ELISA and similar for p181Tau. Spearman coefficients ranged between 0.81 for Aβ1‐40 and 0.96 for p181TAU. Passing‐Bablok analysis showed a systematic and proportional difference for all biomarkers but only systematic for Aβ1‐40. Bland‐Altman analysis showed an average difference between methods in favor of CLEIA. Kappa agreement for single biomarkers were good but lower for Aβ1‐42/Aβ1‐40. Conclusion: We established internal cutoffs to discriminate AD patients from amyloid‐negative SCD individuals. Results obtained by both methods are not interchangeable but showed good agreement. We propose automated CLEIA as a good alternative to manual ELISA together with Aβ1‐42/Aβ1‐40 to classify amyloidosis. [ABSTRACT FROM AUTHOR]
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- 2021
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15. 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.
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Marquié M, García-Sánchez A, Alarcón-Martín E, Martínez J, Castilla-Martí M, Castilla-Martí L, Orellana A, Montrreal L, de Rojas I, García-González P, Puerta R, Olivé C, Cano A, Hernández I, Rosende-Roca M, Vargas L, Tartari JP, Esteban-De Antonio E, Bojaryn U, Ricciardi M, Ariton DM, Pytel V, Alegret M, Ortega G, Espinosa A, Pérez-Cordón A, Sanabria Á, Muñoz N, Lleonart N, Aguilera N, Tárraga L, Valero S, Ruiz A, and Boada M
- 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., Competing Interests: 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., (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.)
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- 2023
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16. Matrix metalloproteinase 10 is linked to the risk of progression to dementia of the Alzheimer's type.
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Martino Adami PV, Orellana A, García P, Kleineidam L, Alarcón-Martín E, Montrreal L, Aguilera N, Espinosa A, Abdelnour C, Rosende-Roca M, Pablo Tartari J, Vargas L, Mauleón A, Esteban-De Antonio E, López-Cuevas R, Dalmasso MC, Campos Martin R, Parveen K, Andrade Fuentes VM, Amin N, Ahmad S, Ikram MA, Lewczuk P, Kornhuber J, Peters O, Frölich L, Rüther E, Wiltfang J, Tarraga L, Boada M, Maier W, de Rojas I, Cano A, Sanabria A, Alegret M, Hernández I, Marquié M, Valero S, van Duijn CM, Wagner M, Jessen F, Schneider A, Sáez Goñi ME, González Pérez A, Ruiz A, and Ramírez A
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- Amyloid beta-Peptides, Biomarkers, Disease Progression, Humans, Longitudinal Studies, Peptide Fragments, tau Proteins, Alzheimer Disease pathology, Cognitive Dysfunction diagnosis, Matrix Metalloproteinase 10 cerebrospinal fluid
- Abstract
Alzheimer's disease has a long asymptomatic phase that offers a substantial time window for intervention. Using this window of opportunity will require early diagnostic and prognostic biomarkers to detect Alzheimer's disease pathology at predementia stages, thus allowing identification of patients who will most probably progress to dementia of the Alzheimer's type and benefit from specific disease-modifying therapies. Consequently, we searched for CSF proteins associated with disease progression along with the clinical disease staging. We measured the levels of 184 proteins in CSF samples from 556 subjective cognitive decline and mild cognitive impairment patients from three independent memory clinic longitudinal studies (Spanish ACE, n = 410; German DCN, n = 93; German Mannheim, n = 53). We evaluated the association between protein levels and clinical stage, and the effect of protein levels on the progression from mild cognitive impairment to dementia of the Alzheimer's type. Mild cognitive impairment subjects with increased CSF level of matrix metalloproteinase 10 (MMP-10) showed a higher probability of progressing to dementia of the Alzheimer's type and a faster cognitive decline. CSF MMP-10 increased the prediction accuracy of CSF amyloid-β 42 (Aβ42), phospho-tau 181 (P-tau181) and total tau (T-tau) for conversion to dementia of the Alzheimer's type. Including MMP-10 to the [A/T/(N)] scheme improved considerably the prognostic value in mild cognitive impairment patients with abnormal Aβ42, but normal P-tau181 and T-tau, and in mild cognitive impairment patients with abnormal Aβ42, P-tau181 and T-tau. MMP-10 was correlated with age in subjects with normal Aβ42, P-tau181 and T-tau levels. Our findings support the use of CSF MMP-10 as a prognostic marker for dementia of the Alzheimer's type and its inclusion in the [A/T/(N)] scheme to incorporate pathologic aspects beyond amyloid and tau. CSF level of MMP-10 may reflect ageing and neuroinflammation., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2022
- Full Text
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17. Association between retinal thickness and β-amyloid brain accumulation in individuals with subjective cognitive decline: Fundació ACE Healthy Brain Initiative.
- Author
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Marquié M, Valero S, Castilla-Marti M, Martínez J, Rodríguez-Gómez O, Sanabria Á, Tartari JP, Monté-Rubio GC, Sotolongo-Grau O, Alegret M, Pérez-Cordón A, Roberto N, de Rojas I, Moreno-Grau S, Montrreal L, Hernández I, Rosende-Roca M, Mauleón A, Vargas L, Abdelnour C, Gil S, Esteban-De Antonio E, Espinosa A, Ortega G, Lomeña F, Pavia J, Vivas A, Tejero MÁ, Gómez-Chiari M, Simó R, Ciudin A, Hernández C, Orellana A, Benaque A, Ruiz A, Tárraga L, and Boada M
- Subjects
- Aged, Brain diagnostic imaging, Brain metabolism, Female, Humans, Male, Middle Aged, Positron-Emission Tomography, Alzheimer Disease diagnosis, Amyloid beta-Peptides metabolism, Cognitive Dysfunction diagnostic imaging, Retina diagnostic imaging, Retina pathology
- 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.
- Published
- 2020
- Full Text
- View/download PDF
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