31 results on '"Hernández, Isabel"'
Search Results
2. The role of sex and gender in the selection of Alzheimer patients for clinical trial pre-screening
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Rosende-Roca, Maitee, Abdelnour, Carla, Esteban, Ester, Tartari, Juan Pablo, Alarcon, Emilio, Martínez-Atienza, Juliana, González-Pérez, Antonio, Sáez, María E., Lafuente, Asunción, Buendía, Mar, Pancho, Ana, Aguilera, Nuria, Ibarria, Marta, Diego, Susana, Jofresa, Sara, Hernández, Isabel, López, Rogelio, Gurruchaga, Miren Jone, Tárraga, Lluís, Valero, Sergi, Ruiz, Agustín, Marquié, Marta, and Boada, Mercè
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- 2021
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3. Altered microRNAs related to synaptic function as potential plasma biomarkers for Alzheimer’s disease
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Siedlecki-Wullich, Dolores, Català-Solsona, Judit, Fábregas, Cristina, Hernández, Isabel, Clarimon, Jordi, Lleó, Alberto, Boada, Merce, Saura, Carlos A., Rodríguez-Álvarez, José, and Miñano-Molina, Alfredo J.
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- 2019
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4. 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, Marta, García-Sánchez, Ainhoa, Alarcón-Martín, Emilio, Martínez, Joan, Castilla-Martí, Miguel, Castilla-Martí, Luis, Orellana, Adelina, Montrreal, Laura, de Rojas, Itziar, García-González, Pablo, Puerta, Raquel, Olivé, Clàudia, Cano, Amanda, Hernández, Isabel, Rosende-Roca, Maitée, Vargas, Liliana, Tartri, Juan Pablo, Antonio, Ester Esteban-De, Bojaryn, Urszula, and Ricciardi, Mario
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MILD cognitive impairment ,ALZHEIMER'S disease ,CEREBROSPINAL fluid ,OPTICAL coherence tomography ,CHRONIC obstructive pulmonary disease - 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) Ab1-42, 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 +4 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. [ABSTRACT FROM AUTHOR]
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- 2023
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5. 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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6. 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, and Sanabria, Ángela
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COGNITION disorders ,ALZHEIMER'S disease ,MILD cognitive impairment ,OPTICAL coherence tomography ,MINI-Mental State Examination - Abstract
Optical coherence tomography angiography (OCT-A) allows the detection of retinal vessel density (VD) loss, which is a reflection of brain vascular pathology. We aimed to investigate differences in macular VD in the superficial plexus in a large cohort of individuals cognitively unimpaired (CU), with mild cognitive impairment due to Alzheimer´s disease (MCI-AD), MCI due to cerebrovascular pathology (MCI-Va), probable Alzheimer´s disease dementia (ADD) and Vascular Dementia (VaD). Clinical, demographical, ophthalmological and OCT-A data from the Neuro-ophthalmology Research at Fundació ACE (NORFACE) project were analyzed. Differences of macular VD in four quadrants (superior, nasal, inferior and temporal) among the five diagnostic groups were assessed in a multivariate regression model, adjusted by age, sex, education, hypertension, diabetes mellitus, heart disease and stroke. The study cohort comprised 672 participants: 128 CU, 120 MCI-AD, 111 MCI-Va, 257 ADD and 56 VaD. Regression analysis showed a significantly higher VD in the temporal quadrant in MCI-AD compared to CU participants (49.05 ± 4.91 vs 47.27 ± 4.17, p = 0.02, d = 0.40), and a significantly lower VD in the inferior quadrant in MCI-Va compared to CU participants (48.70 ± 6.57 vs 51.27 ± 6.39, p = 0.02, d = 0.40). Individuals with heart disease presented significantly lower VD in the inferior quadrant than those without (p = 0.01). The interaction of sex and diagnosis had no effect in differentiating VD. Mini-Mental State Examination (MMSE) scores were not correlated to VD (all r < 0.16; p > 0.07). In conclusion, our study showed that the MCI-AD and MCI-Va groups had significant differences in macular VD in opposite directions in the temporal and inferior quadrants, respectively, compared to CU participants, suggesting that macular VD might be able to differentiate two pathogenic pathways (AD- and cerebrovascular-related) in early stages of cognitive decline. [ABSTRACT FROM AUTHOR]
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- 2022
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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. Automatized FACEmemory® scoring is related to Alzheimer's disease phenotype and biomarkers in early-onset mild cognitive impairment: the BIOFACE cohort.
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Alegret, Montserrat, Sotolongo-Grau, Oscar, de Antonio, Ester Esteban, Pérez-Cordón, Alba, Orellana, Adelina, Espinosa, Ana, Gil, Silvia, Jiménez, Daniel, Ortega, Gemma, Sanabria, Angela, Roberto, Natalia, Hernández, Isabel, Rosende-Roca, Maitee, Tartari, Juan Pablo, Alarcon-Martin, Emilio, de Rojas, Itziar, Montrreal, Laura, Morató, Xavier, Cano, Amanda, and Rentz, Dorene M.
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MILD cognitive impairment ,ALZHEIMER'S disease ,AMNESTIC mild cognitive impairment ,MAGNETIC resonance imaging ,EPISODIC memory - Abstract
Background: FACEmemory® is the first computerized, self-administered verbal episodic memory test with voice recognition. It can be conducted under minimal supervision and contains an automatic scoring system to avoid administrator errors. Moreover, it is suitable for discriminating between cognitively healthy and amnestic mild cognitive impairment (MCI) individuals, and it is associated with Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers. This study aimed to determine whether FACEmemory scoring is related to performance on classical memory tests and to AD biomarkers of brain magnetic resonance imaging (MRI) and CSF in patients with early-onset MCI (EOMCI). Methods: Ninety-four patients with EOMCI from the BIOFACE study completed FACEmemory, classical memory tests (the Spanish version of the Word Free and Cued Selective Reminding Test -FCSRT-, the Word List from the Wechsler Memory Scale, third edition, and the Spanish version of the Rey–Osterrieth Complex Figure Test), and a brain MRI. Eighty-two individuals also underwent a lumbar puncture. Results: FACEmemory scoring was moderately correlated with FCSRT scoring. With regard to neuroimaging MRI results, worse execution on FACEmemory was associated with lower cortical volume in the right prefrontal and inferior parietal areas, along with the left temporal and associative occipital areas. Moreover, the total FACEmemory score correlated with CSF AD biomarkers (Aβ1-42/Aβ1-40 ratio, p181-tau, and Aβ1-42/p181-tau ratio). When performance on FACEmemory was compared among the ATN classification groups, significant differences between the AD group and normal and SNAP groups were found. Conclusions: FACEmemory is a promising tool for detecting memory deficits sensitive to early-onset AD, but it also allows the detection of memory-impaired cases due to other etiologies. Our findings suggest that FACEmemory scoring can detect the AD endophenotype and that it is also associated with AD-related changes in MRI and CSF in patients with EOMCI. The computerized FACEmemory tool might be an opportunity to facilitate early detection of MCI in younger people than 65, who have a growing interest in new technologies. [ABSTRACT FROM AUTHOR]
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- 2022
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9. PLCG2 protective variant p.P522R modulates tau pathology and disease progression in patients with mild cognitive impairment
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KLEINEIDAM, Luca, Chouraki, Vincent, Próchnicki, Tomasz, van der Lee, Sven, Madrid‑Márquez, Laura, Wagner-Thelen, Holger, Karaca, Ilker, WEINHOLD, Leonie, Wolfsgruber, Steffen, Boland, Anne, Martino Adami, Pamela, Lewczuk, Piotr, POPP, Julius, Brosseron, Frederic, Jansen, Iris, HULSMAN, Marc, Kornhuber, Johannes, Peters, Oliver, Berr, Claudine, Heun, Reinhard, Frölich, Lutz, Tzourio, Christophe, Dartigues, Jean-François, Hüll, Michael, Espinosa, Ana, Hernández, Isabel, de Rojas, Itziar, ORELLANA, Adelina, VALERO, Sergi, STRINGA, Najada, Van Schoor, Natasja, Huisman, Martijn, Scheltens, Philip, For The Alzheimer'S Disease Neuroimaging Initiative, (ADNI), Rüther, Eckart, Deleuze, Jean-François, Wiltfang, Jens, Tarraga, Lluis, Schmid, Matthias, Scherer, Martin, Riedel-Heller, Steffi, Heneka, Michael, Amouyel, Philippe, Jessen, Frank, Boada, Merce, Maier, Wolfgang, Schneider, Anja, González‑Pérez, Antonio, van der Flier, Wiesje, Wagner, Michael, Lambert, Jean-Charles, Holstege, Henne, Saez, Mª Eugenia, Latz, Eicke, Ruiz, Agustin, Ramirez, Alfredo, University Hospital Bonn, Universität zu Köln, German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Epidémiologie et de Santé Publique [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Amsterdam UMC, Vrije Universiteit Amsterdam [Amsterdam] (VU), Centro andaluz de estudios bioinformáticos - Andalusian Bioinformatics Research Centre [Sevilla] (CAEBi), Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Universitätsklinikum Erlangen [Erlangen], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), University of Bialystok, Lausanne University Hospital, University hospital of Zurich [Zurich], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Universität Heidelberg [Heidelberg], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Albert-Ludwigs-Universität Freiburg, Universitat Internacional de Catalunya [Barcelona] (UIC), Instituto de Salud Carlos III [Madrid] (ISC), University Medical Center Göttingen (UMG), Universidade de Aveiro, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Universität Leipzig [Leipzig], University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS), Norwegian University of Science and Technology [Trondheim] (NTNU), Norwegian University of Science and Technology (NTNU), Open Access funding provided by Projekt DEAL. This publication was funded in part by the German Federal Ministry of Education and Research (BMBF) (grants KND: 01GI0102, 01GI0420, 01GI0422, 01GI0423, 01GI0429, 01GI0431, 01GI0433, 01GI0434, grants KNDD: 01GI0710, 01GI0711, 01GI0712, 01GI0713, 01GI0714, 01GI0715, 01GI0716, 01ET1006B). Analyses were also funded by the German Federal Ministry of Education and Research (BMBF 01EA1410A) within the project 'Diet-Body-Brain: from epidemiology to evidence-based communication'. Part of the work was funded by the JPND EADB grant (German Federal Ministry of Education and Research (BMBF) grant: 01ED1619A). Part of the analysis was funded by the German Research Foundation (DFG) grant: RA 1971/6-1 to Alfredo Ramirez. Research of the Alzheimer Center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. The Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting VUmc fonds. The clinical database structure was developed with funding from Stichting Dioraphte. Genotyping of the Dutch case–control samples was performed in the context of EADB (European Alzheimer DNA biobank) funded by the JPco-fuND FP-829-029 (ZonMW project number 733051061). Data collection and sharing for this project were funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association, Alzheimer’s Drug Discovery Foundation, Araclon Biotech, BioClinica, Inc., Biogen, Bristol-Myers Squibb Company, CereSpir, Inc., Cogstate, Eisai Inc., ElanPharmaceuticals, Inc., Eli Lilly and Company, EuroImmun, F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc., Fujirebio, GE Healthcare, IXICO Ltd., Janssen Alzheimer Immunotherapy Research and Development, LLC., Johnson and Johnson Pharmaceutical Research and Development LLC., Lumosity, Lundbeck, Merck and Co., Inc., Meso Scale Diagnostics, LLC., NeuroRx Research, Neurotrack Technologies, Novartis Pharmaceuticals Corporation, Pfizer Inc., Piramal Imaging, Servier, Takeda Pharmaceutical Company, and transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for NeuroImaging at the University of Southern California. The Three-City Study genotyping and analysis was funded by the GENMED Labex, the Joint Programming Initiative on Neurodegenerative Diseases Research (JPND, PERADES project), the Institute Pasteur de Lille, the University of Lille, and the Nord-Pas de Calais Regional Council. This work also benefited from the Lille Métropole Communauté Urbaine Council, the French government’s LABEX DISTALZ program (development of innovative strategies for a transdisciplinary approach to Alzheimer’s disease). In addition, the Three-City Study was performed as part of a collaboration between the Institut National de la Santé et de la Recherche Médicale (Inserm), the Victor Segalen Bordeaux II University and Sanofi-Synthélabo. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. Additional funding for the 3C Study was also obtained from the Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé, MGEN, Institut de la Longévité, Agence Française de Sécurité Sanitaire des Produits de Santé, the Aquitaine and Bourgogne Regional Councils, Fondation de France and the joint French Ministry of Research/INSERM 'Cohortes et collections de données biologiques' programme. Lille Génopôle received an unconditional grant from Eisai. Fundacio ACE cohort receives support from the Innovative Medicines Initiative 2 Joint Undertaking which receives support from the European Union’s Horizon 2020 research and innovation programme (ADAPTED Grant No. 115975). A. Ruiz’s research is also supported by Instituto de Salud Carlos III (ISCIII) grants PI13/02434, PI16/01861, and PI19/01301. Acción Estratégica en Salud, integrated in the Spanish National R + D + I Plan and financed by ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER-'Una manera de Hacer Europa'), by Fundación bancaria 'La Caixa' and Grifols SA (GR@ACE project). For the Longitudinal Aging Study Amsterdam (LASA) supports was largely obtained from a grant from the Netherlands Ministry of Health, Welfare and Sports, Directorate of Long-Term Care. The data collection in 2012–2013 was financially supported by the Netherlands Organization for Scientific Research (NWO) in the framework of the project 'New Cohorts of young old in the twenty-first century' (File Number 480-10-014). Genotyping using Axiom-NL array was financially supported by EMGO+ Research Institute. PL was supported by the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement no 115372, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies in kind contribution. JW is supported by an Ilídio Pinho professorship and iBiMED (UID/BIM/04501/2013), at the University of Aveiro, Portugal. JP was supported by a grant from the Swiss National Science Foundation (320030L_141179)., Universität zu Köln = University of Cologne, Amsterdam UMC - Amsterdam University Medical Center, Universität Heidelberg [Heidelberg] = Heidelberg University, Universität Leipzig, Alzheimer's Disease Neuroimaging Initiative (ADNI), Kleineidam, L., Karaca, I., Heneka, M.T., Maier, W., Schneider, A., Wagner, M., Chouraki, V., Amouyel, P., Lambert, J.C., Próchnicki, T., Latz, E., van der Lee, S.J., Jansen, I.E., Hulsman, M., Scheltens, P., van der Flier, W.M., Holstege, H., Madrid-Márquez, L., González-Pérez, A., Sáez, M.E., Wagner-Thelen, H., Martino Adami, P.V., Jessen, F., Ramirez, A., Weinhold, L., Schmid, M., Wolfsgruber, S., Brosseron, F., Boland, A., Deleuze, J.F., Lewczuk, P., Kornhuber, J., Popp, J., Peters, O., Berr, C., Heun, R., Frölich, L., Tzourio, C., Dartigues, J.F., Hüll, M., Espinosa, A., Hernández, I., de Rojas, I., Orellana, A., Valero, S., Ruiz, A., Tarraga, L., Boada, M., Stringa, N., van Schoor, N.M., Huisman, M., Rüther, E., Wiltfang, J., Scherer, M., Riedel-Heller, S., Neurology, Human genetics, Epidemiology and Data Science, APH - Aging & Later Life, APH - Societal Participation & Health, Amsterdam Neuroscience - Complex Trait Genetics, APH - Personalized Medicine, APH - Methodology, Sociology, and The Social Context of Aging (SoCA)
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Apolipoprotein E ,Male ,pathology [Cognitive Dysfunction] ,Cognitive decline ,genetics [Alzheimer Disease] ,Disease ,SEPIA ,pathology [Alzheimer Disease] ,0302 clinical medicine ,Cognition ,genetics [Amyloid beta-Peptides] ,Medicine ,Aged, 80 and over ,0303 health sciences ,education.field_of_study ,Microglia ,physiology [Cognition] ,Middle Aged ,medicine.anatomical_structure ,Disease Progression ,Female ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,analysis [Biomarkers] ,Alzheimer’s disease ,Amyloid ,Phospholipase C gamma 2 ,Population ,tau Proteins ,Pathology and Forensic Medicine ,PLCG2 ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,SDG 3 - Good Health and Well-being ,Alzheimer Disease ,Humans ,Cognitive Dysfunction ,ddc:610 ,education ,Mild cognitive impairment ,HEALTHY ,030304 developmental biology ,Aged ,metabolism [Phospholipase C gamma] ,Original Paper ,Amyloid beta-Peptides ,TREM2 ,business.industry ,Phospholipase C gamma ,genetics [Cognitive Dysfunction] ,metabolism [tau Proteins] ,cerebrospinal fluid [tau Proteins] ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,Immunology ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Biomarkers - Abstract
A rare coding variant (rs72824905, p.P522R) conferring protection against Alzheimer’s disease (AD) was identified in the gene encoding the enzyme phospholipase-C-γ2 (PLCG2) that is highly expressed in microglia. To explore the protective nature of this variant, we employed latent process linear mixed models to examine the association of p.P522R with longitudinal cognitive decline in 3595 MCI patients, and in 10,097 individuals from population-based studies. Furthermore, association with CSF levels of pTau181, total tau, and Aβ1-42 was assessed in 1261 MCI patients. We found that MCI patients who carried the p.P522R variant showed a slower rate of cognitive decline compared to non-carriers and that this effect was mediated by lower pTau181 levels in CSF. The effect size of the association of p.P522R with the cognitive decline and pTau181 was similar to that of APOE-ε4, the strongest genetic risk factor for AD. Interestingly, the protective effect of p.P522R was more pronounced in MCI patients with low Aβ1-42 levels suggesting a role of PLCG2 in the response to amyloid pathology. In line with this hypothesis, we observed no protective effect of the PLCG2 variant on the cognitive decline in population-based studies probably due to the lower prevalence of amyloid positivity in these samples compared to MCI patients. Concerning the potential biological underpinnings, we identified a network of co-expressed proteins connecting PLCG2 to APOE and TREM2 using unsupervised co-regulatory network analysis. The network was highly enriched for the complement cascade and genes differentially expressed in disease-associated microglia. Our data show that p.P522R in PLCG2 reduces AD disease progression by mitigating tau pathology in the presence of amyloid pathology and, as a consequence, maintains cognitive function. Targeting the enzyme PLCG2 might provide a new therapeutic approach for treating AD.
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- 2020
10. 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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11. From Face-to-Face to Home-to-Home: Validity of a Teleneuropsychological Battery.
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Alegret, Montserrat, Espinosa, Ana, Ortega, Gemma, Pérez-Cordón, Alba, Sanabria, Ángela, Hernández, Isabel, Marquié, Marta, Rosende-Roca, Maitée, Mauleón, Ana, Abdelnour, Carla, Vargas, Liliana, de Antonio, Ester Esteban, López-Cuevas, Rogelio, Tartari, Juan Pablo, Alarcón-Martín, Emilio, Tárraga, Lluís, Ruiz, Agustín, Boada, Mercè, and Valero, Sergi
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CONFIRMATORY factor analysis ,EXPLORATORY factor analysis ,MILD cognitive impairment ,FACTOR structure ,NEUROPSYCHOLOGICAL tests ,CLINICAL neuropsychology ,PERCEIVED Stress Scale ,MEMORY ,MEDICAL consultation ,POCKET computers ,ATTENTION ,TELEMEDICINE - Abstract
Background: Over the last decade, teleneuropsychology has increased substantially. There is a need for valid neuropsychological batteries to be administered home-to-home. Since 2006, the neuropsychological battery of Fundació ACE (NBACE) has been administered face-to-face in our clinical settings. Recently, we adapted the NBACE for teleneuropsychology use to be administered home-to-home (NBACEtn).Objective: The aims of the present study are: 1) to determine the home-to-home NBACE equivalence compared to its original face-to-face version; and 2) to examine home-to-home NBACE discriminant capacity by differentiating among cognitively healthy, mild cognitive impairment, or mild dementia subjects and comparing it with the face-to-face version.Methods: Data from 338 individuals assessed home-to-home (NBACEtn) were contrasted with 7,990 participants assessed with its face-to-face version (NBACE). Exploratory and confirmatory factorial structure, and invariance analysis of the two versions of the battery were performed.Results: Exploratory and confirmatory factor analysis supported the four-factor model (attention, memory, executive, and visuospatial/constructional functions). Configural, metric, and scalar measurement invariance was found between home-to-home and face-to-face NBACE versions. Significant differences in most of the neuropsychological variables assessed were observed between the three clinical groups in both versions of administration. No differences were found between the technological devices used by participants (computer or tablet and mobile devices).Conclusion: For the first time, invariance analysis findings were addressed by determining a teleneuropsychological battery's equivalence in comparison with its face-to-face version. This study amplifies the neuropsychological assessment's applicability using a home-to-home format, maintaining the original measure's structure, interpretability, and discriminant capacity. [ABSTRACT FROM AUTHOR]- Published
- 2021
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12. Dementia Care in Times of COVID-19: Experience at Fundació ACE in Barcelona, Spain.
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Benaque, Alba, Gurruchaga, Miren Jone, Abdelnour, Carla, Hernández, Isabel, Cañabate, Pilar, Alegret, Montserrat, Rodríguez, Isabel, Rosende-Roca, Maitee, Tartari, Juan Pablo, Esteban, Ester, López, Rogelio, Gil, Silvia, Vargas, Liliana, Mauleón, Ana, Espinosa, Ana, Ortega, Gemma, Sanabria, Angela, Pérez, Alba, Alarcón, Emilio, and González-Pérez, Antonio
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COVID-19 ,COVID-19 pandemic ,MILD cognitive impairment ,PATIENT safety ,DEMENTIA ,CORONAVIRUS disease treatment ,TREATMENT of dementia ,VIRAL pneumonia ,RESEARCH ,RESEARCH methodology ,PATIENT-centered care ,EVALUATION research ,MEDICAL cooperation ,HOLISTIC medicine ,COMPARATIVE studies ,EPIDEMICS ,TELEMEDICINE ,LONGITUDINAL method - Abstract
Background: Fundació ACE is a non-profit organization providing care based on a holistic model to persons with cognitive disorders and their families for 25 years in Barcelona, Spain. Delivering care to this vulnerable population amidst the COVID-19 pandemic has represented a major challenge to our institution.Objective: To share our experience in adapting our model of care to the new situation to ensure continuity of care.Methods: We detail the sequence of events and the actions taken within Fundació ACE to swiftly adapt our face-to-face model of care to one based on telemedicine consultations. We characterize individuals under follow-up by the Memory Unit from 2017 to 2019 and compare the number of weekly visits in 2020 performed before and after the lockdown was imposed.Results: The total number of individuals being actively followed by Fundació ACE Memory Unit grew from 6,928 in 2017 to 8,147 in 2019. Among those newly diagnosed in 2019, most patients had mild cognitive impairment or mild dementia (42% and 25%, respectively). Weekly visits dropped by 60% following the suspension of face-to-face activity. However, by April 24 we were able to perform 78% of the visits we averaged in the weeks before confinement began.Discussion: We have shown that Fundació ACE model of care has been able to successfully adapt to a health and social critical situation as COVID-19 pandemic. Overall, we were able to guarantee the continuity of care while preserving the safety of patients, families, and professionals. We also seized the opportunity to improve our model of care. [ABSTRACT FROM AUTHOR]- Published
- 2020
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13. Association between retinal thickness and β-amyloid brain accumulation in individuals with subjective cognitive decline: Fundació ACE Healthy Brain Initiative.
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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, and Abdelnour, Carla
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VISUAL fields ,POSITRON emission tomography ,OPTICAL coherence tomography ,MILD cognitive impairment ,ALZHEIMER'S patients ,THICKNESS measurement - 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. [ABSTRACT FROM AUTHOR]
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- 2020
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14. A computerized version of the Short Form of the Face-Name Associative Memory Exam (FACEmemory®) for the early detection of Alzheimer's disease.
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Alegret, Montserrat, Muñoz, Nathalia, Roberto, Natalia, Rentz, Dorene M., Valero, Sergi, Gil, Silvia, Marquié, Marta, Hernández, Isabel, Riveros, Catalina, Sanabria, Angela, Perez-Cordon, Alba, Espinosa, Ana, Ortega, Gemma, Mauleón, Ana, Abdelnour, Carla, Rosende-Roca, Maitee, Papp, Kathryn V., Orellana, Adela, Benaque, Alba, and Tarraga, Lluís
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ALZHEIMER'S disease ,COGNITION disorders ,AUTOMATIC speech recognition ,MILD cognitive impairment ,EPISODIC memory - Abstract
Background: Computerized neuropsychological tests for early detection of Alzheimer's disease (AD) have attracted increasing interest. Memory for faces and proper names is a complex task because its association is arbitrary. It implicates associative occipito-temporal cerebral regions, which are disrupted in AD. The short form of the Face-Name Associative Memory Exam (FNAME-12), developed to detect preclinical and prodromal AD, asks individuals to learn the names and occupations associated with 12 faces. The current work advances this field by using voice recognition and touchscreen response format. The purpose of this study is to create the first self-administered episodic memory test, FACEmemory®, by adapting the FNAME-12 for tablet use with voice recognition, touchscreen answers, and automatic scoring. The test was minimally supervised by a psychologist to avoid technological problems during execution and scored manually to assess the reliability of the automatic scoring. The aims of the present study were (1) to determine whether FACEmemory® is a sensitive tool for the detection of cognitive impairment, (2) to examine whether performances on FACEmemory® are correlated with those on the S-FNAME (paper-and-pencil version with 16 images), and (3) to determine whether performances on FACEmemory® are related to AD biomarkers in the cerebrospinal fluid (CSF) (Aβ42, p-tau, and Aβ42/p-tau ratio). Methods: FACEmemory® was completed by 154 cognitively healthy (CH) individuals and 122 subjects with mild cognitive impairment, of whom 61 were non-amnestic (naMCI) and 61 amnestic (aMCI). A subsample of 65 individuals completed the S-FNAME, and 65 subjects received lumbar punctures. Results: Performance on FACEmemory® was progressively worse from CH to the naMCI and aMCI groups. A cutoff of 31.5 in total FACEmemory® obtained 80.5% and 80.3% sensitivity and specificity values, respectively, for discriminating between CH and aMCI. Automatically corrected FACEmemory® scores were highly correlated with the manually corrected ones. FACEmemory® scores and AD CSF biomarker levels were significantly correlated as well, mainly in the aMCI group. Conclusions: FACEmemory® may be a promising memory prescreening tool for detecting subtle memory deficits related to AD. Our findings suggest FACEmemory® performance provides a useful gradation of impairment from normal aging to aMCI, and it is related to CSF AD biomarkers. [ABSTRACT FROM AUTHOR]
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- 2020
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15. Exploring Genetic Associations of Alzheimer's Disease Loci With Mild Cognitive Impairment Neurocognitive Endophenotypes.
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Espinosa, Ana, Hernández-Olasagarre, Begoña, Moreno-Grau, Sonia, Kleineidam, Luca, Heilmann-Heimbach, Stefanie, Hernández, Isabel, Wolfsgruber, Steffen, Wagner, Holger, Rosende-Roca, Maitée, Mauleón, Ana, Vargas, Liliana, Lafuente, Asunción, Rodríguez-Gómez, Octavio, Abdelnour, Carla, Gil, Silvia, Marquié, Marta, Santos-Santos, Miguel A., Sanabria, Ángela, Ortega, Gemma, and Monté-Rubio, Gemma
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- 2018
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16. The Role of Verb Fluency in the Detection of Early Cognitive Impairment in Alzheimer's Disease.
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Alegret, Montserrat, Peretó, Mar, Pérez, Alba, Valero, Sergi, Espinosa, Ana, Ortega, Gemma, Hernández, Isabel, Mauleón, Ana, Rosende-Roca, Maitée, Vargas, Liliana, Rodríguez-Gómez, Octavio, Abdelnour, Carla, Berthier, Marcelo L, Bak, Thomas H, Ruíz, Agustín, Tárraga, Lluís, and Boada, Mercè
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ALZHEIMER'S disease risk factors ,ALZHEIMER'S disease diagnosis ,MILD cognitive impairment ,FLUENCY (Language learning) ,VERBAL ability ,COGNITION ,DIAGNOSIS - Abstract
Background: Verb fluency (VF) is the less commonly used fluency test, despite several studies suggesting its potential as a neuropsychological assessment tool.Objective: To investigate the presence of VF deficits in mild cognitive impairment (MCI) and mild Alzheimer's disease (AD) dementia; to assess the usefulness of VF in the detection of cognitively healthy (CH) people who will convert to MCI, and from MCI to dementia; and to establish the VF cut-offs useful in the cognitive assessment of Spanish population.Methods: 568 CH, 885 MCI, and 367 mild AD dementia individuals were administered the VF test and a complete neuropsychological battery. Longitudinal analyses were performed in 231 CH and 667 MCI subjects to search for VF predictors of diagnosis conversion.Results: A worsening on VF performance from CH, MCI to AD dementia groups was found. Lower performances on VF were significantly related to conversion from CH to MCI/MCI to dementia. When the effect of time to conversion was analyzed, a significant effect of VF was found on the faster conversion from CH to MCI, but not from MCI to dementia. Moreover, VF cut-off scores and sensitivity/specificity values were calculated for 6 conditions (3 age ranges by 2 educational levels).Conclusion: The VF test may be a useful tool for the differential diagnosis of cognitive failure in the elderly. Since VF deficits seem to take place in early stages of the disease, it is a suitable neuropsychological tool for the detection not only of CH people who will convert to MCI, but also from MCI to dementia. [ABSTRACT FROM AUTHOR]- Published
- 2018
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17. Social Representation of Dementia: An Analysis of 5,792 Consecutive Cases Evaluated in a Memory Clinic.
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Cañabate, Pilar, Martínez, Gabriel, Rosende-Roca, Maitée, Moreno, Mariola, Preckler, Silvia, Valero, Sergi, Sotolongo, Oscar, Hernández, Isabel, Alegret, Montserrat, Ortega, Gemma, Espinosa, Ana, Mauleón, Ana, Vargas, Liliana, Rodríguez, Octavio, Abdelnour, Carla, Sánchez, Domingo, Martín, Elvira, Ruiz, Agustín, Tárraga, Lluís, and Boada, Mercè
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DEMENTIA ,MILD cognitive impairment ,COGNITION disorders ,MEDICAL care ,PUBLIC health - Abstract
Background: Different interpretations of cognitive impairment and dementia due to differences in health structures, such as cultural differences could affect the diagnosis and treatment of the condition. it is reasonable to expect that the social and family impact of the disease and coping strategies will differ among societies.Objective: The general aim of this study is to understand the social representations of dementia, its associated practices, and the effects they imply.Methods: People diagnosed with clinical dementia and their families were assessed from 2005 to 2015 in the memory clinic of the Fundació ACE, Institut Català de Neurociències Aplicades in Barcelona, Spain.Results: 9,898 people were examined and 5,792 were diagnosed with dementia. For those with a caregiver (71%), the decision-making fell on the person with dementia in 16.2% of the cases; and for those without a caregiver, in 26.4% of the cases the family did not perceive the deficits as a disease, which led to multiple risk situations (74.6%).Conclusions: The recognition of dementia as part of aging is common among families. Consequently, risk situations may arise and diagnosis and access to treatment may be delayed. The incorporation of a social appraisal to the diagnostic process is a necessity to evaluate these situations. [ABSTRACT FROM AUTHOR]- Published
- 2017
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18. Cognitive Composites Domain Scores Related to Neuroimaging Biomarkers within Probable-Amnestic Mild Cognitive Impairment-Storage Subtype.
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Espinosa, Ana, Alegret, Montserrat, Pesini, Pedro, Valero, Sergi, Lafuente, Asunción, Buendía, Mar, José, Itziar San, Ibarria, Marta, Tejero, Miguel A., Giménez, Joan, Ruiz, Susana, Hernández, Isabel, Pujadas, Francesc, Martínez-Lage, Pablo, Munuera, Josep, Arbizu, Javier, Tárraga, Lluis, Hendrix, Suzanne B., Ruiz, Agustín, and Becker, James T.
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MILD cognitive impairment ,ALZHEIMER'S disease ,NEUROPSYCHOLOGICAL tests ,BRAIN imaging ,MAGNETIC resonance imaging ,ALZHEIMER'S disease diagnosis ,BRAIN metabolism ,AMINES ,ANTHROPOMETRY ,BRAIN ,DEOXY sugars ,MEMORY ,NEURORADIOLOGY ,RADIOPHARMACEUTICALS ,RESEARCH funding ,SURVIVAL analysis (Biometry) ,THIAZOLES ,POSITRON emission tomography ,EARLY diagnosis ,PSYCHOLOGY - Abstract
The probable-amnestic (Pr-a) mild cognitive impairment (MCI)-storage subtype is a phenotype with 8.5 times more risk of conversion to dementia, mainly Alzheimer's disease (AD), than the possible non-amnestic (Pss-na) MCI. The aim of this study was to find the optimized cognitive composites (CCs) domain scores most related to neuroimaging biomarkers within Pr-aMCI-storage subtype patients. The Fundació ACE (ACE) study with 20 Pr-aMCI-storage subtype subjects (MCI) were analyzed. All subjects underwent a neuropsychological assessment, a structural MRI, FDG-PET, and PIB-PET. The adjusted hippocampal volume (aHV) on MRI, the standard uptake value ratio (SUVR) on FDG-PET and PIB-PET SUVR measures were analyzed. The construction of the CCs domain scores, and the aHV on MRI and FDG-PET SUVR measures, were replicated in the parental AB255 study database (n = 133 MCI). Partial correlations adjusted by age, gender, and education were calculated with the associated p-value among every CC domain score and the neuroimaging biomarkers. The results were replicated in the "MCI due to AD" with memory storage impairments from ADNI. Delayed Recall CC domain score was significantly correlated with PIB-PET SUVR (β= -0.61, p = 0.003) in the ACE study and also with aHV on MRI (β= 0.27, p = 0.01) and FDG-PET SUVR (β= 0.27, p = 0.01) in the AB255 study. After a median survival time of 20.6 months, 85% from the ACE MCI converted to AD. The replication of our results in the ADNI dataset also confirmed our findings. Delayed Recall is the CC domain score best correlated with neuroimaging biomarkers associated with prodromal AD diagnosis. [ABSTRACT FROM AUTHOR]
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- 2017
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19. Impact of Recruitment Methods in Subjective Cognitive Decline.
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Abdelnour, Carla, Rodríguez-Gómez, Octavio, Alegre, Montserrat, Valero, Sergi, Moreno-Grau, Sonia, Ángela, Sanabria, Hernández, Isabel, Rosende-Roca, Maitee, Vargas, Liliana, Mauleón, Ana, Sánchez, Domingo, Espinosa, Ana, Ortega, Gemma, Pérez-Cordón, Alba, Diego, Susana, Gailhajanet, Anna, Guitart, Marina, Sotolongo-Grau, Óscar, Ruiz, Agustín, and Tárraga, Lluiz
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MILD cognitive impairment ,ALZHEIMER'S disease ,DEMENTIA ,LOGISTIC regression analysis ,NEUROPSYCHOLOGY ,APOLIPOPROTEINS ,COMPARATIVE studies ,DISEASE susceptibility ,NEUROPSYCHOLOGICAL tests ,RESEARCH methodology ,MEDICAL cooperation ,RESEARCH ,SEX distribution ,EVALUATION research ,EDUCATIONAL attainment ,PATIENT selection ,SELF diagnosis - Abstract
Background: Recruitment methods can determine sample characteristics in mild cognitive impairment and Alzheimer's disease dementia, but little is known about its influence in subjective cognitive decline (SCD).Objective: To determine the influence of two types of recruitment methods in the characteristics of individuals with SCD.Methods: We select and compare clinical and neuropsychological features, and frequency of APOE ɛ4 allele of 326 subjects with SCD from two cohorts: Open House Initiative (OHI) versus Memory Unit (MU). A logistic regression analysis (LRA), using gender and years of education as covariates, was used to examine the neuropsychological variables.Results: The OHI sample were mostly women (75.9% versus 64.5%, p < 0.05), with higher educational level (12.15 [3.71] versus 10.70 [3.80] years, p = 0.001), and more family history of dementia (138 [62.7%] versus 44 [41.5%], p < 0.001) than the MU sample. Also, the OHI sample showed better overall neuropsychological performance than the MU sample, and after a LRA, this trend continued in automatic response inhibition capacity, abstract reasoning, and recognition memory. We did not find differences in age, depression history, and/or APOE ɛ4 allele frequency.Conclusion: SCD subjects showed different demographic and neuropsychological characteristics depending on the recruitment method, which should be taken into account in the design of research studies with this target population. [ABSTRACT FROM AUTHOR]- Published
- 2017
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20. Alzheimer's disease risk variants modulate endophenotypes in mild cognitive impairment.
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Louwersheimer, Eva, Wolfsgruber, Steffen, Espinosa, Ana, Lacour, André, Heilmann-Heimbach, Stefanie, Alegret, Montserrat, Hernández, Isabel, Rosende-Roca, Maitée, Tárraga, Lluís, Boada, Mercè, Kornhuber, Johannes, Peters, Oliver, Frölich, Lutz, Hüll, Michael, Rüther, Eckart, Wiltfang, Jens, Scherer, Martin, Riedel-Heller, Steffi, Jessen, Frank, and Nöthen, Markus M.
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Introduction We evaluated the effect of Alzheimer's disease (AD) susceptibility loci on endophenotypes closely related with AD pathology in patients with mild cognitive impairment (MCI). Methods We selected 1730 MCI patients from four independent data sets. Weighted polygenic risk scores (PGS) were constructed of 18 non-apolipoprotein E ( APOE ) AD risk variants. In addition, we determined APOE genotype. AD endophenotypes were cognitive decline over time and cerebrospinal fluid (CSF) biomarkers (aβ, tau, ptau). Results PGS was modestly associated with cognitive decline over time, as measured by mini-mental state examination (MMSE) (β ± SE:−0.24 ± 0.10; P = .012), and with CSF levels of tau and ptau (tau: 1.38 ± 0.36, P = 1.21 × 10 −4 ; ptau: 1.40 ± 0.36, P = 1.02 × 10 −4 ). Discussion In MCI, we observed a joint effect of AD susceptibility loci on nonamyloid endophenotypes, suggesting a link of these genetic loci with neuronal degeneration in general rather than with Alzheimer-related amyloid deposition. [ABSTRACT FROM AUTHOR]
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- 2016
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21. Concordance between Subjective and Objective Memory Impairment in Volunteer Subjects.
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Alegret, Montserrat, Rodríguez, Octavio, Espinosa, Ana, Ortega, Gemma, Sanabria, Angela, Valero, Sergi, Hernández, Isabel, Rosende-Roca, Maitée, Vargas, Liliana, Abdelnour, Carla, Mauleón, Ana, Gailhajanet, Anna, Martín, Elvira, Tárraga, Lluís, Rentz, Dorene M., Amariglio, Rebecca E., Ruíz, Agustín, and Boada, Mercè
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MEMORY disorders ,COGNITIVE testing ,ASSOCIATIVE memory (Psychology) ,ALZHEIMER'S disease ,MILD cognitive impairment ,FOLLOW-up studies (Medicine) - Abstract
Background: Subjective memory impairment (SMI) refers to subjective awareness of initial memory decline undetectable with existing standardized cognitive tests. The Face Name Associative Memory Exam (FNAME) was created to detect memory deficits in individuals with preclinical Alzheimer's disease (AD). We reported normative data of a Spanish version of FNAME (S-FNAME) in cognitively normal (CN) Spanish-speaking subjects >49.Objective: To determine whether higher SMI [a modification of Memory Failures Everyday (MFE-30)] was related to worse memory performance (S-FNAME) or associated with greater affective symptoms in subjects >49; and whether MFE-30 and FNAME were able to discriminate between CN and mild cognitive impairment (MCI) subjects.Methods: 317 subjects (CN = 196, MCI = 121) were included in the analysis because they attended the annual "Open House Initiative" at Memory Clinic Fundació ACE, were >49 years, literate, received S-FNAME, MFE-30, and Hospital Anxiety and Depression Scale, had Mini-Mental State Examination scores ≥27, and returned to complete a comprehensive diagnostic assessment.Results: MFE-30 scores were associated with affective symptoms but not with S-FNAME performance. S-FNAME scores were related to performance on memory variables of NBACE (neuropsychological battery used in Fundació ACE). Although the MCI group showed significantly higher MFE-30 and worse S-FNAME scores than the CN group, their discriminability values were similar (Sensitivity: 49.6 versus 52.9; Specificity: 85.1 versus 83.6, respectively).Conclusions: SMI was more related to depressive symptoms than to S-FNAME memory performance; and S-FNAME scores were related to other episodic memory test performances, but neither to affective symptoms nor to SMI. MFE-30 and S-FNAME are not optimal for discriminating between CN and MCI groups. Longitudinal follow-up will determine if lower S-FNAME and higher SMI are related to increased risk of AD. [ABSTRACT FROM AUTHOR]- Published
- 2015
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22. Cognitive, Genetic, and Brain Perfusion Factors Associated with Four Year Incidence of Alzheimer's Disease from Mild Cognitive Impairment.
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Alegret, Montserrat, Cuberas-Borrós, Gemma, Espinosa, Ana, Valero, Sergi, Hernández, Isabel, Ruíz, Agustín, Becker, James T., Rosende-Roca, Maitée, Mauleón, Ana, Sotolongo, Oscar, Castell-Conesa, Joan, Roca, Isabel, Tárraga, Lluís, and Boada, Mercè
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MILD cognitive impairment ,ALZHEIMER'S disease research ,NEUROPSYCHOLOGICAL tests ,BRAIN imaging ,BRAIN research - Abstract
Background: There is a range of factors that predict the development of Alzheimer's disease (AD) dementia among patients with amnestic mild cognitive impairment (MCI). Objectives: To identify the neuropsychological, genetic, and functional brain imaging data that best predict conversion to AD dementia in patients with amnestic MCI. Methods: From an initial group of 42 amnestic MCI patients assessed with neurological, neuropsychological, and brain SPECT, 39 (25 converters, 14 non-converters) were followed for 4 years, and 36 had APOE ε4 genotyping. Baseline neuropsychological data and brain SPECT data were used to predict which of the MCI patients would develop dementia by the end of the 4 years of observation. Results: The MCI patients who had converted to AD dementia had poorer performance on long-term visual memory and Semantic Fluency tests. The MCI subjects who developed dementia were more likely to carry at least one copy of the APOE ε4 allele (Hazard Risk = 4.22). There was lower brain perfusion in converters than non-converters, mainly in postcentral gyrus. An additional analysis of the SPECT data found differences between the MCI subjects and controls in the posterior cingulate gyrus and the basal forebrain. When the brain imaging and neuropsychological test data were combined in the same Cox regression model, only the neuropsychological test data were significantly associated with time to dementia. Conclusion: Although the presence of reduced brain perfusion in postcentral gyrus and basal forebrain indicated an at-risk condition, it was the extent of memory impairment that was linked to the speed of decline from MCI to AD. [ABSTRACT FROM AUTHOR]
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- 2014
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23. Cut-off Scores of a Brief Neuropsychological Battery (NBACE) for Spanish Individual Adults Older than 44 Years Old.
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Alegret, Montserrat, Espinosa, Ana, Valero, Sergi, Vinyes-Junqué, Georgina, Ruiz, Agustín, Hernández, Isabel, Rosende-Roca, Maitee, Mauleón, Ana, Becker, James T., Tárraga, Lluís, and Boada, Mercè
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NEUROPSYCHOLOGY ,OLDER people ,MILD cognitive impairment ,INFORMATION processing ,DEMENTIA ,VERBAL learning ,THERAPEUTICS - Abstract
The neuropsychological battery used in Fundació ACE (NBACE) is a relatively brief, and easy to administer, test battery that was designed to detect cognitive impairment in the adulthood. The NBACE includes measures of cognitive information processing speed, orientation, attention, verbal learning and memory, language, visuoperception, praxis and executive functions. The aim of the present study was to establish the cut-off scores for impairment for different levels of age and education that could be useful in the cognitive assessment of Spanish subjects who are at risk for cognitive impairment, especially dementia. Data from 1018 patients with a mild dementia syndrome, and 512 cognitively healthy subjects, older than 44 years, from the Memory Clinic of Fundació ACE (Barcelona, Spain) were analyzed. In the whole sample, cut-off scores and sensitivity/specificity values were calculated for six conditions after combining 3 age ranges (44 to 64; 65 to 74; and older than 74 years old) by 2 educational levels (until Elementary school; and more than Elementary school). Moreover, general cut-offs are reported for Catalan and Spanish speakers. The results showed that most of NBACE tests reached good sensitivity and specificity values, except for Ideomotor praxis, Repetition and Verbal Comprehension tests, which had a ceiling effect. Word List Learning from the Wechsler Memory Scale-III and Semantic Verbal Fluency were the most useful tests to discriminate between cognitively healthy and demented subjects. The NBACE has been shown to be a useful tool able to detect cognitive impairment, especially dementia, in older than 44 years Spanish persons. [ABSTRACT FROM AUTHOR]
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- 2013
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24. A Longitudinal Follow-Up of 550 Mild Cognitive Impairment Patients: Evidence for Large Conversion to Dementia Rates and Detection of Major Risk Factors Involved.
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Espinosa, Ana, Alegret, Montserrat, Valero, Sergi, Vinyes-Junqué, Georgina, Hernández, Isabel, Mauleón, Ana, Rosende-Roca, Maitée, Ruiz, Agustín, López, Oscar, Tárraga, Lluís, and Boada, Mercè
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COGNITION disorders research ,ALZHEIMER'S patients ,NEUROPSYCHOLOGICAL tests ,EPISODIC memory ,MEMORY disorders ,DEMENTIA risk factors - Abstract
The most recent studies about mild cognitive impairment (MCI) are focused on the search for factors that make patients more vulnerable to conversion to dementia, mainly Alzheimer's disease (AD). The aim of this study was to determine which neuropsychological test performances, including episodic memory profiles, and genetic risk factors (APOE ε4) better predict early conversion to dementia among the four MCI subtypes. Data from 550 MCI patients were analyzed for the purpose of this study and were classified according to Petersen's criteria (2004), and also taking into account the absence (probable MCI) or presence (possible MCI) of comorbidities that could explain cognitive deficits. MCI cases were divided into Probable amnestic (Pr-aMCI) (n = 115), probable non-amnestic (Pr-naMCI) (n = 37), possible amnestic (Pss-aMCI) (n = 234), and possible non-amnestic (Pss-naMCI) (n = 164), single or multiple domain. In the whole MCI sample, regression analysis showed that low performances on Orientation, Verbal Delayed Recall of the Word List Learning test from WMS-III, and Luria's Clock test were associated with conversion to dementia, independently of APOE ε4 allele. Cox proportional-hazards showed that the Probable MCI subtype, presence of storage memory impairment, multiple domain condition, and presence of at least one ε4 allele increased the risk of conversion to dementia. Multivariate survival and Kapplan-Meier analyses showed that the Pr-aMCI with storage memory impairment had the most and closest risk of conversion to dementia. In conclusion, the Pr-aMCI subset of patients had 8.5 times more risk of converting to dementia than the Pss-naMCI group, who displayed the slowest conversion rate to dementia. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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25. A Two-Year Follow-Up of Cognitive Deficits and Brain Perfusion in Mild Cognitive Impairment and Mild Alzheimer's Disease.
- Author
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Alegret, Montserrat, Cuberas-Borrós, Gemma, Vinyes-Junqué, Georgina, Espinosa, Ana, Valero, Sergi, Hernández, Isabel, Roca, Isabel, Ruíz, Agustín, Rosende-Roca, Maitée, Mauleón, Ana, Becker, James T., Castell-Conesa, Joan, Tárraga, Lluís, and Boada, Mercè
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ALZHEIMER'S disease ,MILD cognitive impairment ,SINGLE photon emission computerized tomography centers ,LONGITUDINAL method ,PATIENTS - Abstract
The 15-Objects Test (15-OT) provides useful gradation of visuoperceptual impairment from normal aging through Alzheimer's disease (AD) and correlates with temporo-parietal perfusion. The objectives of this study were to analyze progression of 15-OT performance in mild cognitive impairment (MCI) and AD, and its correlates with cognition and single photon emission computerized tomography (SPECT), as well as to examine neuropsychological and SPECT differences between the MCI patients who developed AD and those who did not. From the initial 126 participants (42/group), 38 AD, 39 MCI, and 38 elderly controls (EC) were reassessed (SPECT: 35 AD, 33 MCI, 35 EC) after two years. The progression of cognitive and SPECT scores during this period was compared between groups, and baseline data between converters and non-converters. The 15-OT was the only measure of progression that differed between the three groups; worsening scores on 15-OT were associated with worsening in verbal and visual retention, and decreased perfusion on left postsubicular area. In the MCI patients, cerebral perfusion fell over the two years in medial-posterior cingulate and fronto-temporo-parietal regions; AD showed extensive changes involving almost all cerebral regions. No SPECT changes were detected in controls. At baseline, the MCI patients who developed AD differed from non-converters in verbal recognition memory, but not in SPECT perfusion. In conclusion, SPECT and 15-OT appear to provide a potential measure to differentiate between normal aging, MCI, and AD. Worsening on 15-OT was related to decreased perfusion in postsubicular area; but further longitudinal studies are needed to determine the contribution of 15-OT as a predictor of AD from MCI. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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26. Brain Perfusion Correlates of Visuoperceptual Deficits in Mild Cognitive Impairment and Mild Alzheimer's Disease.
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Alegret, Montserrat, Vinyes-Junqué, Georgina, Boada, Mercè, Martínez-Lage, Pablo, Cuberas, Gemma, Espinosa, Ana, Roca, Isabel, Hernández, Isabel, Valero, Sergi, Rosende-Roca, Maitée, Mauleón, Ana, Becker, James T., and Tárraga, Lluís
- Subjects
ALZHEIMER'S disease research ,VISUAL perception ,COGNITION disorders ,PERFUSION ,DIAGNOSIS ,ANALYSIS of variance - Abstract
Visuoperceptual processing is impaired early in the clinical course of Alzheimer's disease (AD). The 15-Objects Test (15-OT) detects such subtle performance deficits in mild cognitive impairment (MCI) and mild AD. Reduced brain perfusion in the temporal, parietal, and prefrontal regions have been found in early AD and MCI patients. The objectives of this study were to confirm the role of the 15-OT in the diagnosis of MCI and AD and to investigate the brain perfusion correlates of visuoperceptual dysfunction (15-OT) in subjects with MCI, AD, and normal aging. Forty-two AD, 42 MCI, and 42 healthy elderly control subjects underwent a brain Single Photon Emission Tomography (SPECT) and separately completed the 15-OT. An analysis of variance compared 15-OT scores between groups. SPM5 was used to analyse the SPECT data. 15-OT performace was impaired in the MCI and AD patients. In terms of the SPECT scans, AD patients showed reduced perfusion in temporal-parietal regions, while the MCI subjects had decreased perfusion in the middle and posterior cingulate. When MCI and AD groups were compared, a significant brain perfusion reduction was found in temporo-parietal regions. In the whole sample, 15-OT performance was significantly correlated with the clinical dementia rating scores, and with the perfusion in the bilateral posterior cingulate and the right temporal pole, with no significant correlation in each separate group. Our findings suggest that the 15-OT performance provides a useful gradation of impairment from normal aging to AD, and it seems to be related to perfusion in the bilateral posterior cingulate and the right temporal pole. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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27. Detection of visuoperceptual deficits in preclinical and mild Alzheimer's disease.
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Alegret, Montse, Boada-Rovira, Mercè, Vinyes-Junqué, Georgina, Valero, Sergi, Espinosa, Ana, Hernández, Isabel, Modinos, Gemma, Rosende-Roca, Maitee, Mauleón, Ana, Becker, JamesT., and Tárraga, Lluís
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NEUROPSYCHOLOGICAL tests ,VISUAL agnosia ,MEMORY ,PATIENTS ,ALZHEIMER'S disease ,REGRESSION analysis ,MULTIVARIATE analysis - Abstract
Exhaustive neuropsychological assessment of mild cognitive impairment (MCI) subjects frequently identifies cognitive deficits other than memory. However, visuoperception has rarely been investigated in MCI. The 15-Objects Test (15-OT), a visual discrimination task based on the Poppelreuter Test, consists of 15 overlapping objects. Poppelreuter-type tests are frequently used to detect visual agnosia. However, more complex tests, such as the 15-OT, are required to detect visuoperceptual signs in those patients who perform correctly on simple tests. The aim of the present study was to investigate visuoperceptual deficits in MCI patients and to assess the usefulness of the 15-OT to discriminate Alzheimer's disease (AD) and MCI patients from controls. The 15-OT, and a neuropsychological battery included in the diagnostic assessment, was administered to 44 healthy controls, 44 MCI patients, and 44 mild AD patients. Performance on the 15-OT was significantly different between groups. MCI scored between AD and controls. When MCI and AD patients had relatively normal performance on simple tests (Poppelreuter), increased significant abnormalities were found by a more difficult visuoperceptual test (15-OT). Regression analyses showed that the 15-OT was a significant predictor of group membership, but the Poppelreuter Test did not significantly contribute to the models. Visuoperceptual processing is impaired early in the clinical course of AD. The 15-OT allows detection of visuoperceptual deficits in the preclinical and mild AD stages, when classical tests are still unable to detect subtle deficits. So, its inclusion in neuropsychological batteries that are nowadays used in the clinical practice would allow increasing their diagnostic potential. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
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28. Author Correction: 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, Maiteé, Alegret, Montse, Pérez‑Cordón, Alba, Ortega, Gemma, Roberto, Natalia, Sanabria, Angela, Abdelnour, Carla, Gil, Silvia, Tartari, Juan Pablo, Vargas, Liliana, and Antonio, Ester Esteban‑De
- Subjects
NEUROBEHAVIORAL disorders ,MILD cognitive impairment - Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
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29. Association of lysophosphatidic acids with cerebrospinal fluid biomarkers and progression to Alzheimer's disease.
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Ahmad, Shahzad, Orellana, Adelina, Kohler, Isabelle, Frölich, Lutz, de Rojas, Itziar, Gil, Silvia, Boada, Mercè, Hernández, Isabel, Hausner, Lucrezia, Bakker, Margot H. M., Cabrera-Socorro, Alfredo, Amin, Najaf, Ramírez, Alfredo, Ruiz, Agustín, Hankemeier, Thomas, and Van Duijn, Cornelia M.
- Subjects
LYSOPHOSPHOLIPIDS ,ALZHEIMER'S disease ,CEREBROSPINAL fluid ,TAU proteins ,LIQUID chromatography-mass spectrometry ,MILD cognitive impairment - Abstract
Background: Lysophosphatidic acids (LPAs) are bioactive signaling phospholipids that have been implicated in Alzheimer's disease (AD). It is largely unknown whether LPAs are associated with AD pathology and progression from mild cognitive impairment (MCI) to AD. Methods: The current study was performed on cerebrospinal fluid (CSF) and plasma samples of 182 MCI patients from two independent cohorts. We profiled LPA-derived metabolites using liquid chromatography-mass spectrometry. We evaluated the association of LPAs with CSF biomarkers of AD, Aβ-42, p-tau, and total tau levels overall and stratified by APOE genotype and with MCI to AD progression. Results: Five LPAs (C16:0, C16:1, C22:4, C22:6, and isomer-LPA C22:5) showed significant positive association with CSF biomarkers of AD, Aβ-42, p-tau, and total tau, while LPA C14:0 and C20:1 associated only with Aβ-42 and alkyl-LPA C18:1, and LPA C20:1 associated with tau pathology biomarkers. Association of cyclic-LPA C16:0 and two LPAs (C20:4, C22:4) with Aβ-42 levels was found only in APOE ε4 carriers. Furthermore, LPA C16:0 and C16:1 also showed association with MCI to AD dementia progression, but results did not replicate in an independent cohort. Conclusions: Our findings provide evidence that LPAs may contribute to early AD pathogenesis. Future studies are needed to determine whether LPAs play a role in upstream of AD pathology or are downstream markers of neurodegeneration. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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30. Blood Amyloid Beta Levels in Healthy, Mild Cognitive Impairment and Alzheimer’s Disease Individuals: Replication of Diastolic Blood Pressure Correlations and Analysis of Critical Covariates.
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Ruiz, Agustín, Pesini, Pedro, Espinosa, Ana, Pérez-Grijalba, Virginia, Valero, Sergi, Sotolongo-Grau, Oscar, Alegret, Montserrat, Monleón, Inmaculada, Lafuente, Asunción, Buendía, Mar, Ibarria, Marta, Ruiz, Susana, Hernández, Isabel, San José, Itziar, Tárraga, Lluís, Boada, Mercè, and Sarasa, Manuel
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AMYLOID beta-protein ,BLOOD testing ,MILD cognitive impairment ,ALZHEIMER'S disease ,BLOOD pressure ,BIOMARKERS ,CONTROL groups - Abstract
Plasma amyloid beta (Aβ) levels are being investigated as potential biomarkers for Alzheimer’s disease. In AB128 cross-sectional study, a number of medical relevant correlates of blood Aβ40 or Aβ42 were analyzed in 140 subjects (51 Alzheimer’s disease patients, 53 healthy controls and 36 individuals diagnosed with mild cognitive impairment). We determined the association between multiple variables with Aβ40 and Aβ42 levels measured in three different blood compartments called i) Aβ directly accessible (DA) in the plasma, ii) Aβ recovered from the plasma matrix (RP) after diluting the plasma sample in a formulated buffer, and iii) associated with the remaining cellular pellet (CP). We confirmed that diastolic blood pressure (DBP) is consistently correlated with blood DA Aβ40 levels (r=-0.19, P=0.032). These results were consistent in the three phenotypic groups studied. Importantly, the observation resisted covariation with age, gender or creatinine levels. Observed effect size and direction of Aβ40 levels/DBP correlation are in accordance with previous reports. Of note, DA Aβ40 and the RP Aβ40 were also strongly associated with creatinine levels (r=0.599, P<<0.001) and to a lesser extent to urea, age, hematocrit, uric acid and homocysteine (p<0.001). DBP and the rest of statistical significant correlates identified should be considered as potential confounder factors in studies investigating blood Aβ levels as potential AD biomarker. Remarkably, the factors affecting Aβ levels in plasma (DA, RP) and blood cell compartments (CP) seem completely different. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
31. Assessing the role of TUBA4A gene in frontotemporal degeneration.
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Dols-Icardo, Oriol, Iborra, Oriol, Valdivia, Jessica, Pastor, Pau, Ruiz, Agustín, de Munain, Adolfo López, Sánchez-Valle, Raquel, Álvarez, Victoria, Sánchez-Juan, Pascual, Lleó, Alberto, Fortea, Juan, Blesa, Rafael, Cardona, Fernando, Baquero, Miquel, Alonso, María Dolores, Ortega-Cubero, Sara, Pastor, María A., Razquin, Cristina, Boada, Mercè, and Hernández, Isabel
- Subjects
- *
TUBULIN genetics , *FRONTOTEMPORAL lobar degeneration , *AMYOTROPHIC lateral sclerosis , *MILD cognitive impairment , *MISSENSE mutation , *DIAGNOSIS - Abstract
The tubulin alpha 4a ( TUBA4A ) gene has been recently associated with amyotrophic lateral sclerosis. Interestingly, some of the mutation carriers were also diagnosed with frontotemporal degeneration (FTD) or mild cognitive impairment. With the aim to investigate the role of TUBA4A in FTD, we screened TUBA4A in a series of 814 FTD patients from Spain. Our data did not disclose any nonsense or missense variant in the cohort, thus suggesting that TUBA4A mutations are not associated with FTD. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
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