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1. Automatic analysis of Categorical Verbal Fluency for Mild Cognitive Impartment detection: a non-linear language independent approach

Author

López-De-Ipiña, Karmele, de Lizarduy, Unai Martinez, Barroso, Nora, Ecay-Torres, Miriam, Martinez-Lage, Pablo, Torres, Fernando, and Faundez-Zanuy, Marcos

Subjects
Computer Science - Sound, Electrical Engineering and Systems Science - Audio and Speech Processing, Quantitative Biology - Quantitative Methods
Abstract

Alzheimer's disease (AD) is one the main causes of dementia in the world and the patients develop severe disability and sometime full dependence. In previous stages Mild Cognitive Impairment (MCI) produces cognitive loss but not severe enough to interfere with daily life. This work, on selection of biomarkers from speech for the detection of AD, is part of a wide-ranging cross study for the diagnosis of Alzheimer. Specifically in this work a task for detection of MCI has been used. The task analyzes Categorical Verbal Fluency. The automatic classification is carried out by SVM over classical linear features, Castiglioni fractal dimension and Permutation Entropy. Finally the most relevant features are selected by ANOVA test. The promising results are over 50% for MCI, Comment: 4 pages, published in 2015 4th International Work Conference on Bioinspired Intelligence (IWOBI), pp. 101-104

Published
2022
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2. Paired plasma lipidomics and proteomics analysis in the conversion from mild cognitive impairment to Alzheimer's disease

Author

Gómez-Pascual, Alicia, Naccache, Talel, Xu, Jin, Hooshmand, Kourosh, Wretlind, Asger, Gabrielli, Martina, Lombardo, Marta Tiffany, Shi, Liu, Buckley, Noel J., Tijms, Betty M., Vos, Stephanie J.B., ten Kate, Mara, Engelborghs, Sebastiaan, Sleegers, Kristel, Frisoni, Giovanni B., Wallin, Anders, Lleó, Alberto, Popp, Julius, Martinez-Lage, Pablo, Streffer, Johannes, Barkhof, Frederik, Zetterberg, Henrik, Visser, Pieter Jelle, Lovestone, Simon, Bertram, Lars, Nevado-Holgado, Alejo J., Gualerzi, Alice, Picciolini, Silvia, Proitsi, Petroula, Verderio, Claudia, Botía, Juan A., and Legido-Quigley, Cristina

Published
2024
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4. World-Wide FINGERS Network: A global approach to risk reduction and prevention of dementia.

Author

Kivipelto, Miia, Mangialasche, Francesca, Snyder, Heather M, Allegri, Ricardo, Andrieu, Sandrine, Arai, Hidenori, Baker, Laura, Belleville, Sylvie, Brodaty, Henry, Brucki, Sonia M, Calandri, Ismael, Caramelli, Paulo, Chen, Christopher, Chertkow, Howard, Chew, Effie, Choi, Seong H, Chowdhary, Neerja, Crivelli, Lucía, Torre, Rafael De La, Du, Yifeng, Dua, Tarun, Espeland, Mark, Feldman, Howard H, Hartmanis, Maris, Hartmann, Tobias, Heffernan, Megan, Henry, Christiani J, Hong, Chang H, Håkansson, Krister, Iwatsubo, Takeshi, Jeong, Jee H, Jimenez-Maggiora, Gustavo, Koo, Edward H, Launer, Lenore J, Lehtisalo, Jenni, Lopera, Francisco, Martínez-Lage, Pablo, Martins, Ralph, Middleton, Lefkos, Molinuevo, José L, Montero-Odasso, Manuel, Moon, So Y, Morales-Pérez, Kristal, Nitrini, Ricardo, Nygaard, Haakon B, Park, Yoo K, Peltonen, Markku, Qiu, Chengxuan, Quiroz, Yakeel T, Raman, Rema, Rao, Naren, Ravindranath, Vijayalakshmi, Rosenberg, Anna, Sakurai, Takashi, Salinas, Rosa M, Scheltens, Philip, Sevlever, Gustavo, Soininen, Hilkka, Sosa, Ana L, Suemoto, Claudia K, Tainta-Cuezva, Mikel, Velilla, Lina, Wang, Yongxiang, Whitmer, Rachel, Xu, Xin, Bain, Lisa J, Solomon, Alina, Ngandu, Tiia, and Carrillo, Maria C

Subjects
Alzheimer's disease, World-Wide FINGERS, cognitive impairment, dementia, lifestyle, multidomain intervention, prevention, randomized controlled trial, Geriatrics, Clinical Sciences, Neurosciences
Abstract

Reducing the risk of dementia can halt the worldwide increase of affected people. The multifactorial and heterogeneous nature of late-onset dementia, including Alzheimer's disease (AD), indicates a potential impact of multidomain lifestyle interventions on risk reduction. The positive results of the landmark multidomain Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) support such an approach. The World-Wide FINGERS (WW-FINGERS), launched in 2017 and including over 25 countries, is the first global network of multidomain lifestyle intervention trials for dementia risk reduction and prevention. WW-FINGERS aims to adapt, test, and optimize the FINGER model to reduce risk across the spectrum of cognitive decline-from at-risk asymptomatic states to early symptomatic stages-in different geographical, cultural, and economic settings. WW-FINGERS aims to harmonize and adapt multidomain interventions across various countries and settings, to facilitate data sharing and analysis across studies, and to promote international joint initiatives to identify globally implementable and effective preventive strategies.

Published
2020

5. Gray matter network properties show distinct associations with CSF p-tau 181 levels and amyloid status in individuals without dementia

Author

Lorenzini, Luigi, Ingala, Silvia, Wottschel, Viktor, Wink, Alle Meije, Mutsaerts, Henk JMM, Haller, Sven, Blennow, Kaj, O'Brien, John T., Frisoni, B. Giovanni, Chételat, Gael, Payoux, Pierre, Martinez-Lage, Pablo, Waldman, Adam, Wardlaw, Joanna, Ritchie, Craig, Gispert, Juan Domingo, Visser, Pieter Jelle, Scheltens, Philip, Barkhof, Frederik, and Tijms, Betty M.

Published
2022
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7. Unlocking Preclinical Alzheimer's: A Multi-Year Label-Free In Vitro Raman Spectroscopy Study Empowered by Chemometrics.

Author

Lopez, Eneko, Etxebarria-Elezgarai, Jaione, García-Sebastián, Maite, Altuna, Miren, Ecay-Torres, Mirian, Estanga, Ainara, Tainta, Mikel, López, Carolina, Martínez-Lage, Pablo, Amigo, Jose Manuel, and Seifert, Andreas

Subjects
ALZHEIMER'S disease, AUTOPSY, CHEMOMETRICS, NEURODEGENERATION, CEREBROSPINAL fluid, RAMAN spectroscopy
Abstract

Alzheimer's disease is a progressive neurodegenerative disorder, the early detection of which is crucial for timely intervention and enrollment in clinical trials. However, the preclinical diagnosis of Alzheimer's encounters difficulties with gold-standard methods. The current definitive diagnosis of Alzheimer's still relies on expensive instrumentation and post-mortem histological examinations. Here, we explore label-free Raman spectroscopy with machine learning as an alternative to preclinical Alzheimer's diagnosis. A special feature of this study is the inclusion of patient samples from different cohorts, sampled and measured in different years. To develop reliable classification models, partial least squares discriminant analysis in combination with variable selection methods identified discriminative molecules, including nucleic acids, amino acids, proteins, and carbohydrates such as taurine/hypotaurine and guanine, when applied to Raman spectra taken from dried samples of cerebrospinal fluid. The robustness of the model is remarkable, as the discriminative molecules could be identified in different cohorts and years. A unified model notably classifies preclinical Alzheimer's, which is particularly surprising because of Raman spectroscopy's high sensitivity regarding different measurement conditions. The presented results demonstrate the capability of Raman spectroscopy to detect preclinical Alzheimer's disease for the first time and offer invaluable opportunities for future clinical applications and diagnostic methods. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Discovery and validation of plasma proteomic biomarkers relating to brain amyloid burden by SOMAscan assay

Author

Shi, Liu, Westwood, Sarah, Baird, Alison L., Winchester, Laura, Dobricic, Valerija, Kilpert, Fabian, Hong, Shengjun, Franke, Andre, Hye, Abdul, Ashton, Nicholas J., Morgan, Angharad R., Bos, Isabelle, Vos, Stephanie J.B., Buckley, Noel J., Kate, Mara ten, Scheltens, Philip, Vandenberghe, Rik, Gabel, Silvy, Meersmans, Karen, Engelborghs, Sebastiaan, De Roeck, Ellen E., Sleegers, Kristel, Frisoni, Giovanni B., Blin, Olivier, Richardson, Jill C., Bordet, Régis, Molinuevo, José L., Rami, Lorena, Wallin, Anders, Kettunen, Petronella, Tsolaki, Magda, Verhey, Frans, Lleó, Alberto, Alcolea, Daniel, Popp, Julius, Peyratout, Gwendoline, Martinez-Lage, Pablo, Tainta, Mikel, Johannsen, Peter, Teunissen, Charlotte E., Freund-Levi, Yvonne, Frölich, Lutz, Legido-Quigley, Cristina, Barkhof, Frederik, Blennow, Kaj, Zetterberg, Henrik, Baker, Susan, Morgan, B. Paul, Streffer, Johannes, Visser, Pieter Jelle, Bertram, Lars, Lovestone, Simon, and Nevado-Holgado, Alejo J.

Published
2019
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10. Inflammatory biomarkers in Alzheimer's disease plasma

Author

Bullmore, Edward T., Bhatti, Junaid, Chamberlain, Samuel J., Correia, Marta M., Crofts, Anna L., Dickinson, Amber, Foster, Andrew C., Kitzbichler, Manfred G., Knight, Clare, Lynall, Mary-Ellen, Maurice, Christina, O'Donnell, Ciara, Pointon, Linda J., St George Hyslop, Peter, Turner, Lorinda, Vertes, Petra, Widmer, Barry, Williams, Guy B., Morgan, B. Paul, Leckey, Claire A., Morgan, Angharad R., O'Hagan, Caroline, Touchard, Samuel, Cavanagh, Jonathan, Deith, Catherine, Farmer, Scott, McClean, John, McColl, Alison, McPherson, Andrew, Scouller, Paul, Sutherland, Murray, Boddeke, H.W.G.M., Richardson, Jill C., Khan, Shahid, Murphy, Phil, Parker, Christine A., Patel, Jai, Jones, Declan, de Boer, Peter, Kemp, John, Drevets, Wayne C., Nye, Jeffrey S., Wittenberg, Gayle, Isaac, John, Bhattacharya, Anindya, Carruthers, Nick, Kolb, Hartmuth, Pariante, Carmine M., Turkheimer, Federico, Barker, Gareth J., Byrom, Heidi, Cash, Diana, Cattaneo, Annamaria, Gee, Antony, Hastings, Caitlin, Mariani, Nicole, McLaughlin, Anna, Mondelli, Valeria, Nettis, Maria, Nikkheslat, Naghmeh, Randall, Karen, Sheridan, Hannah, Simmons, Camilla, Singh, Nisha, Van Loo, Victoria, Vicente-Rodriguez, Marta, Wood, Tobias C., Worrell, Courtney, Zajkowska, Zuzanna, Plath, Niels, Egebjerg, Jan, Eriksson, Hans, Gastambide, Francois, Adams, Karen Husted, Jeggo, Ross, Thomsen, Christian, Pederson, Jan Torleif, Campbell, Brian, Möller, Thomas, Nelson, Bob, Zorn, Stevin, O'Connor, Jason, Attenburrow, Mary Jane, Baird, Alison, Benjamin, Jithen, Clare, Stuart, Cowen, Philip, Huang, I-Shu (Dante), Hurley, Samuel, Jones, Helen, Lovestone, Simon, Mada, Francisca, Nevado-Holgado, Alejo, Oladejo, Akintayo, Ribe, Elena, Smith, Katy, Vyas, Anviti, Hughes, Zoe, Balice-Gordon, Rita, Duerr, James, Piro, Justin R., Sporn, Jonathan, Perry, V. Hugh, Cleal, Madeleine, Fryatt, Gemma, Gomez-Nicola, Diego, Mancuso, Renzo, Reynolds, Richard, Harrison, Neil A., Cercignani, Mara, Clarke, Charlotte L., Hoskins, Elizabeth, Kohn, Charmaine, Murray, Rosemary, Wilcock, Lauren, Wlazly, Dominika, Mount, Howard, Leckey, Claire, Nevado-Holgado, Alejo J., Barkhof, Frederik, Bertram, Lars, Blin, Olivier, Bos, Isabelle, Dobricic, Valerija, Engelborghs, Sebastiaan, Frisoni, Giovanni, Frölich, Lutz, Gabel, Silvey, Johannsen, Peter, Kettunen, Petronella, Kłoszewska, Iwona, Legido-Quigley, Cristina, Lleó, Alberto, Martinez-Lage, Pablo, Mecocci, Patrizia, Meersmans, Karen, Molinuevo, José Luis, Peyratout, Gwendoline, Popp, Julius, Richardson, Jill, Sala, Isabel, Scheltens, Philip, Streffer, Johannes, Soininen, Hikka, Tainta-Cuezva, Mikel, Teunissen, Charlotte, Tsolaki, Magda, Vandenberghe, Rik, Visser, Pieter Jelle, Vos, Stephanie, Wahlund, Lars-Olof, Wallin, Anders, Westwood, Sarah, and Zetterberg, Henrik

Published
2019
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11. Primary fatty amides in plasma associated with brain amyloid burden, hippocampal volume, and memory in the European Medical Information Framework for Alzheimer's Disease biomarker discovery cohort

Author

Kim, Min, Snowden, Stuart, Suvitaival, Tommi, Ali, Ashfaq, Merkler, David J., Ahmad, Tahmina, Westwood, Sarah, Baird, Alison, Proitsi, Petroula, Nevado-Holgado, Alejo, Hye, Abdul, Bos, Isabelle, Vos, Stephanie, Vandenberghe, Rik, Teunissen, Charlotte, ten Kate, Mara, Scheltens, Philip, Gabel, Silvy, Meersmans, Karen, Blin, Olivier, Richardson, Jill, De Roeck, Ellen, Sleegers, Kristel, Bordet, Régis, Rami, Lorena, Kettunen, Petronella, Tsolaki, Magda, Verhey, Frans, Sala, Isabel, Lléo, Alberto, Peyratout, Gwendoline, Tainta, Mikel, Johannsen, Peter, Freund-Levi, Yvonne, Frölich, Lutz, Dobricic, Valerija, Engelborghs, Sebastiaan, Frisoni, Giovanni B., Molinuevo, José L., Wallin, Anders, Popp, Julius, Martinez-Lage, Pablo, Bertram, Lars, Barkhof, Frederik, Ashton, Nicholas, Blennow, Kaj, Zetterberg, Henrik, Streffer, Johannes, Visser, Pieter J., Lovestone, Simon, and Legido-Quigley, Cristina

Published
2019
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12. Longitudinal cerebrospinal fluid biomarker trajectories along the Alzheimer's disease continuum in the BIOMARKAPD study

Author

Lleó, Alberto, Alcolea, Daniel, Martínez-Lage, Pablo, Scheltens, Philip, Parnetti, Lucilla, Poirier, Judes, Simonsen, Anja H., Verbeek, Marcel M., Rosa-Neto, Pedro, Slot, Rosalinde E.R., Tainta, Mikel, Izaguirre, Andrea, Reijs, Babette L.R., Farotti, Lucia, Tsolaki, Magda, Vandenbergue, Rik, Freund-Levi, Yvonne, Verhey, Frans R.J., Clarimón, Jordi, Fortea, Juan, Frolich, Lutz, Santana, Isabel, Molinuevo, José Luis, Lehmann, Sylvain, Visser, Pieter J., Teunissen, Charlotte E., Zetterberg, Henrik, and Blennow, Kaj

Published
2019
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13. Cerebrospinal fluid biomarkers of neurodegeneration, synaptic integrity, and astroglial activation across the clinical Alzheimer's disease spectrum

Author

Bos, Isabelle, Vos, Stephanie, Verhey, Frans, Scheltens, Philip, Teunissen, Charlotte, Engelborghs, Sebastiaan, Sleegers, Kristel, Frisoni, Giovanni, Blin, Olivier, Richardson, Jill C., Bordet, Régis, Tsolaki, Magda, Popp, Julius, Peyratout, Gwendoline, Martinez-Lage, Pablo, Tainta, Mikel, Lleó, Alberto, Johannsen, Peter, Freund-Levi, Yvonne, Frölich, Lutz, Vandenberghe, Rik, Westwood, Sarah, Dobricic, Valerija, Barkhof, Frederik, Legido-Quigley, Cristina, Bertram, Lars, Lovestone, Simon, Streffer, Johannes, Andreasson, Ulf, Blennow, Kaj, Zetterberg, Henrik, and Visser, Pieter Jelle

Published
2019
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16. Cortical microstructural changes along the Alzheimer's disease continuum

Author

Montal, Victor, Vilaplana, Eduard, Alcolea, Daniel, Pegueroles, Jordi, Pasternak, Ofer, González-Ortiz, Sofia, Clarimón, Jordi, Carmona-Iragui, María, Illán-Gala, Ignacio, Morenas-Rodríguez, Estrella, Ribosa-Nogué, Roser, Sala, Isabel, Sánchez-Saudinós, María-Belén, García-Sebastian, Maite, Villanúa, Jorge, Izagirre, Andrea, Estanga, Ainara, Ecay-Torres, Mirian, Iriondo, Ane, Clerigue, Montserrat, Tainta, Mikel, Pozueta, Ana, González, Andrea, Martínez-Heras, Eloy, Llufriu, Sara, Blesa, Rafael, Sanchez-Juan, Pascual, Martínez-Lage, Pablo, Lleó, Alberto, and Fortea, Juan

Published
2018
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17. Whitepaper: Defining and investigating cognitive reserve, brain reserve, and brain maintenance

Author

Arenaza Urquiljo, Eider M., Bartrés-Faz, David, Belleville, Sylvie, Cantillon, Marc, Chetelat, Gael, Clouston, Sean A.P., Estanga, Ainara, Ewers, Michael, Franzmeier, Nicolai, Gold, Brian, Habeck, Christian, Jones, Richard, Kempermann, Gerd, Kochhann, Renata, Kremen, William, Lim, Yen Ying, Martínez-Lage, Pablo, Morbelli, Silvia, Okonkwo, Ozioma, Ossenkoppele, Rik, Pettigrew, Corinne, Rosen, Allyson C., Scarmeas, Nikolaos, Soldan, Anja, Song, Xiaowei, Udeh-Momoh, Chinedu, Stern, Yaakov, Valenzuela, Michael, Van Loenhoud, Anita C., Vemuri, Prashanthi, Vuoksimaa, Eero, Arenaza-Urquijo, Eider M., Cantilon, Marc, and Kremen, William S.

Published
2018
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24. Feature Extraction Approach Based on Fractal Dimension for Spontaneous Speech Modelling Oriented to Alzheimer Disease Diagnosis

Author

López-de-Ipiña, Karmele, Egiraun, Harkaitz, Sole-Casals, Jordi, Ecay, Miriam, Ezeiza, Aitzol, Barroso, Nora, Martinez-Lage, Pablo, Martinez-de-Lizardui, Unai, Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Doug, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Goebel, Randy, editor, Siekmann, Jörg, editor, Wahlster, Wolfgang, editor, Drugman, Thomas, editor, and Dutoit, Thierry, editor

Published
2013
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26. Mechanisms underlying resilience in ageing

Author

Stern, Yaakov, Chételat, Gaël, Habeck, Christian, Arenaza-Urquijo, Eider M., Vemuri, Prashanthi, Estanga, Ainara, Bartrés-Faz, David, Cantillon, Marc, Clouston, Sean A.P., Elman, Jeremy A., Gold, Brian T., Jones, Richard, Kempermann, Gerd, Lim, Yen Ying, van Loenhoud, Anita, Martínez-Lage, Pablo, Morbelli, Silvia, Okonkwo, Ozioma, Ossenkoppele, Rik, Pettigrew, Corinne, Rosen, Allyson C., Scarmeas, Nikolaos, Soldan, Anja, Udeh-Momoh, Chinedu, Valenzuela, Michael, and Vuoksimaa, Eero

Published
2019
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28. Genetic screening of Alzheimer's disease genes in Iberian and African samples yields novel mutations in presenilins and APP

Author

Guerreiro, Rita Joao, Baquero, Miquel, Blesa, Rafael, Boada, Mercè, Brás, Jose Miguel, Bullido, Maria J., Calado, Ana, Crook, Richard, Ferreira, Carla, Frank, Ana, Gómez-Isla, Teresa, Hernández, Isabel, Lleó, Alberto, Machado, Alvaro, Martínez-Lage, Pablo, Masdeu, José, Molina-Porcel, Laura, Molinuevo, José L., Pastor, Pau, Pérez-Tur, Jordi, Relvas, Rute, Oliveira, Catarina Resende, Ribeiro, Maria Helena, Rogaeva, Ekaterina, Sa, Alfredo, Samaranch, Lluís, Sánchez-Valle, Raquel, Santana, Isabel, Tàrraga, Lluís, Valdivieso, Fernando, Singleton, Andrew, Hardy, John, and Clarimón, Jordi

Published
2010
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30. Changes in Synaptic Proteins Precede Neurodegeneration Markers in Preclinical Alzheimer's Disease Cerebrospinal Fluid

Author

Lleó, Alberto, Núñez-Llaves, Raúl, Alcolea, Daniel, Chiva, Cristina, Balateu Paños, Daniel, Colom-Cadena, Martí, Gómez, Gemma, Muñoz, Laia, Querol-Vilaseca, Marta, Pegueroles, Jordi, Rami Gonzalez, Lorena, Llado Plarrumani, Albert, Molinuevo, José Luis, Tainta, Mikel, Clarimón, Jordi, Spires Jones, Tara, Blesa, Rafael, Fortea, Juan, Martínez Lage, Pablo, Sánchez Valle, Raquel, Sabidó, Eduard, Bayés, Àlex, Belbin, Olivia, and Universitat Autònoma de Barcelona

Subjects
Male, Proteomics, Pathology, medicine.medical_specialty, Prodromal Symptoms, Syntaxin 1, Nerve Tissue Proteins, Disease, Biochemistry, Analytical Chemistry, Synapse, 03 medical and health sciences, Cerebrospinal fluid, Alzheimer Disease, Interstitial fluid, medicine, Humans, Receptors, AMPA, Shotgun proteomics, Molecular Biology, Aged, 030304 developmental biology, 0303 health sciences, business.industry, Research, Calcium-Binding Proteins, 030302 biochemistry & molecular biology, Neurodegeneration, Prognosis, medicine.disease, Pathophysiology, Biomarker (cell), Alzheimer, Malaltia d', Early Diagnosis, Synapses, Thy-1 Antigens, Female, Autopsy, business, Proteïnes, Biomarkers
Abstract

A biomarker of synapse loss, an early event in Alzheimer's disease (AD) pathophysiology that precedes neuronal death and symptom onset, would be a much-needed prognostic biomarker. With direct access to the brain interstitial fluid, the cerebrospinal fluid (CSF) is a potential source of synapse-derived proteins. In this study, we aimed to identify and validate novel CSF biomarkers of synapse loss in AD. Discovery: Combining shotgun proteomics of the CSF with an exhaustive search of the literature and public databases, we identified 251 synaptic proteins, from which we selected 22 for further study. Verification: Twelve proteins were discarded because of poor detection by Selected Reaction Monitoring (SRM). We confirmed the specific expression of 9 of the remaining proteins (Calsynytenin-1, GluR2, GluR4, Neurexin-2A, Neurexin-3A, Neuroligin-2, Syntaxin-1B, Thy-1, Vamp-2) at the human synapse using Array Tomography microscopy and biochemical fractionation methods. Exploration: Using SRM, we monitored these 9 synaptic proteins (20 peptides) in a cohort of CSF from cognitively normal controls and subjects in the pre-clinical and clinical AD stages (n = 80). Compared with controls, peptides from 8 proteins were elevated 1.3 to 1.6-fold (p < 0.04) in prodromal AD patients. Validation: Elevated levels of a GluR4 peptide at the prodromal stage were replicated (1.3-fold, p = 0.04) in an independent cohort (n = 60). Moreover, 7 proteins were reduced at preclinical stage 1 (0.6 to 0.8-fold, p < 0.04), a finding that was replicated (0.7 to 0.8-fold, p < 0.05) for 6 proteins in a third cohort (n = 38). In a cross-cohort meta-analysis, 6 synaptic proteins (Calsyntenin-1, GluR4, Neurexin-2A, Neurexin-3A, Syntaxin-1B and Thy-1) were reduced 0.8-fold (p < 0.05) in preclinical AD, changes that precede clinical symptoms and CSF markers of neurodegeneration. Therefore, these proteins could have clinical value for assessing disease progression, especially in preclinical stages of AD. This work was supported by the following research grants: Fondos de Investigaciones Sanitarias (PI15/00058, PI14/01561, PI18/000327) from the “Fondo Europeo de Desarrollo Regional (FEDER)”, Unión Europea, “Una manera de hacer Europa” and the “Instituto de Salud Carlos III, Ministerio de Economia y Competitividad, Gobierno de España” (ISCIII). Additional funding came from the “Departament de Salut, Generalitat de Cataluña - Pla Estratègic de Recerca i Innovació en Salut (PERIS) 2016 –2020, 2017–2019” (SLT002/16/00408, 2017SGR547), “Programa 1 Enfermedad de Alzheimer y otras demencias degenerativas” from the Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), the “Fundació Bancaria La Caixa” (4560/6393) and “La Marató” organized by the television channel, TV3 (20142610). OB is supported by the Miguel Servet program (CP13/00091) from the ISCIII and FEDER. AB is supported by the Ministerio de Economia y Competitividad, Gobierno de España and FEDER (BFU2012-34398 and BFU2015-69717-P), by the Career Integration Grant from the European Union (ref. 304111, Marie Curie Actions), by the Ramón y Cajal Fellowship (ref. RYC-2011-08391) from the Ministerio de Economia y Competitividad, Gobierno de España and by the CERCA Programme from the Generalitat de Catalunya. RN-L is supported by the research grant from the Generalitat de Catalunya (PERIS SLT/2381/2016/00099). The proteomics analyses were performed in the CRG/UPF Proteomics Unit which is part of the Proteored, PRB3 and is supported by grant PT17/0019, of the PE IDi 2013–2016, funded by ISCIII and ERDF

Published
2019

31. Accelerated long-term forgetting in individuals with subjective cognitive decline and amyloid-β positivity.

Author

Tort‐Merino, Adrià, Valech, Natalia, Laine, Matti, Olives, Jaume, León, María, Ecay‐Torres, Mirian, Estanga, Ainara, Martínez‐Lage, Pablo, Fortea, Juan, Molinuevo, José Luis, Sánchez‐Valle, Raquel, Rodriguez‐Fornells, Antoni, Rami, Lorena, Tort-Merino, Adrià, Ecay-Torres, Mirian, Martínez-Lage, Pablo, Sánchez-Valle, Raquel, and Rodriguez-Fornells, Antoni

Subjects
RECOLLECTION (Psychology), ALZHEIMER'S disease, CEREBROSPINAL fluid, OPTIMISM, MEDICAL research, RESEARCH, RESEARCH methodology, EVALUATION research, NEUROPSYCHOLOGICAL tests, COMPARATIVE studies, QUESTIONNAIRES, RESEARCH funding, PEPTIDES
Abstract

Objectives: We studied a sample of cognitively unimpaired individuals, with and without subjective cognitive decline (SCD), in order to investigate accelerated long-term forgetting (ALF) and to explore the relationships between objective and subjective cognitive performance and cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers.Methods: Fifty-two individuals were included and SCD was quantified through the Subjective Cognitive Decline Questionnaire (SCD-Q), using its validated cutoff to classify participants as Low SCD-Q (n = 21) or High SCD-Q (n = 31). These groups were further subdivided according to the presence or absence of abnormal levels of CSF Aβ42 . Objective cognitive performance was assessed with the Ancient Farming Equipment Test (AFE-T), a new highly-demanding test that calls for acquisition and retention of novel object/name pairs and allows measuring ALF over a 6-month period.Results: The High SCD-Q group showed a significantly higher free forgetting rate at 3 months compared to the Low SCD-Q (F [1,44] = 4.72; p < 0.05). When stratifying by amyloid status, High SCD-Q/Aβ+ showed a significantly lower performance than High SCD-Q/Aβ-on the final free and cued learning scores (F [1,27] = 6.44, p < 0.05 and F [1,27] = 7.51, p < 0.05, respectively), the 1-week free and cued recall (F [1,24] = 4.49; p < 0.05 and F [1,24] = 7.10; p < 0.01, respectively), the 1-week cued forgetting rate (F [1,24] = 5.13; p < 0.05), and the 3-month cued recall (F [1,24] = 4.27; p < 0.05). Linear regression analyses showed that higher SCD-Q scores were associated with higher forgetting rates on the AFE-T (β = -0.212; p < 0.05).Conclusions: It is possible to detect ALF in individuals with high SCD ratings, appearing especially in those with abnormal CSF Aβ42 levels. Both in research and the clinical field, there is an increasing need of using more demanding cognitive measures, such as the AFE-T, for identifying and tracking the earliest cognitive changes in these populations. [ABSTRACT FROM AUTHOR]

Published
2021
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33. Accelerated long‐term forgetting over three months in asymptomatic APOE ɛ4 carriers

Author

Tort‐Merino, Adrià, primary, Laine, Matti, additional, Valech, Natalia, additional, Olives, Jaume, additional, León, María, additional, Ecay‐Torres, Mirian, additional, Estanga, Ainara, additional, Martínez‐Lage, Pablo, additional, Fortea, Juan, additional, Sánchez‐Valle, Raquel, additional, Rami, Lorena, additional, and Rodríguez‐Fornells, Antoni, additional

Published
2020
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35. Autores

Author

Prado, Juan Álvarez Linera, primary, Arellano Cabornero, Jon I., additional, Galindo, Francisco Barceló, additional, Alabart, Nuria Bargalló, additional, García, Esther Blanc, additional, Alonso, Raúl Cabestrero, additional, Calvo-Merino, Beatriz, additional, Martínez-Lage, Pablo Campo, additional, Giménez, Joan Camprodón, additional, and González, Almudena Capilla, additional

Published
2008
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36. A metabolite-based machine learning approach to diagnose Alzheimer-type dementia in blood: Results from the European Medical Information Framework for Alzheimer disease biomarker discovery cohort

Author

Stamate, Daniel, Kim, Min, Proitsi, Petroula, Westwood, Sarah, Baird, Alison, Nevado-Holgado, Alejo, Hye, Abdul, Bos, Isabelle, Vos, Stephanie J.B., Vandenberghe, Rik, Teunissen, Charlotte E., Kate, Mara Ten, Scheltens, Philip, Gabel, Silvy, Meersmans, Karen, Blin, Olivier, Richardson, Jill, De Roeck, Ellen, Engelborghs, Sebastiaan, Sleegers, Kristel, Bordet, Régis, Ramit, Lorena, Kettunen, Petronella, Tsolaki, Magda, Verhey, Frans, Alcolea, Daniel, Lléo, Alberto, Peyratout, Gwendoline, Tainta, Mikel, Johannsen, Peter, Freund-Levi, Yvonne, Frölich, Lutz, Dobricic, Valerija, Frisoni, Giovanni B., Molinuevo, José L., Wallin, Anders, Popp, Julius, Martinez-Lage, Pablo, Bertram, Lars, Blennow, Kaj, Zetterberg, Henrik, Streffer, Johannes, Visser, Pieter J., Lovestone, Simon, and Legido-Quigley, Cristina

Published
2019
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37. Plasma lipids are associated with white matter microstructural changes and axonal degeneration

Author

Iriondo, Ane, primary, García-Sebastian, Maite, additional, Arrospide, Arantzazu, additional, Arriba, Maria, additional, Aurtenetxe, Sara, additional, Barandiaran, Myriam, additional, Clerigue, Montserrat, additional, Ecay-Torres, Mirian, additional, Estanga, Ainara, additional, Gabilondo, Alazne, additional, Izagirre, Andrea, additional, Saldias, Jon, additional, Tainta, Mikel, additional, Villanua, Jorge, additional, Mar, Javier, additional, Goñi, Felix M., additional, and Martínez-Lage, Pablo, additional

Published
2020
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38. Cerebrospinal Fluid 7-Ketocholesterol Level is Associated with Amyloid-β42 and White Matter Microstructure in Cognitively Healthy Adults

Author

Iriondo, Ane, primary, García-Sebastian, Maite, additional, Arrospide, Arantzazu, additional, Arriba, Maria, additional, Aurtenetxe, Sara, additional, Barandiaran, Myriam, additional, Clerigue, Montserrat, additional, Ecay-Torres, Mirian, additional, Estanga, Ainara, additional, Gabilondo, Alazne, additional, Izagirre, Andrea, additional, Saldias, Jon, additional, Tainta, Mikel, additional, Villanua, Jorge, additional, Blennow, Kaj, additional, Zetterberg, Henrik, additional, Mar, Javier, additional, Abad-García, Beatriz, additional, Dias, Irundika H.K., additional, Goñi, Felix M., additional, and Martínez-Lage, Pablo, additional

Published
2020
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40. Cognitive Composites Domain Scores Related to Neuroimaging Biomarkers within Probable-Amnestic Mild Cognitive Impairment-Storage Subtype

Author

Espinosa, Ana, Alegret, Montserrat, Pesini, Pedro, Valero Ventura, Sergi, Lafuente, Asunción, Buendía, Mar, San José, Itziar, Ibarria, Marta, Tejero, Miguel Ángel, Giménez Ruiz, Joan, Ruiz, Susana, Hernández, Isabel, Pujadas, Francesc, Martínez Lage, Pablo, Munuera, Josep, Arbizu, Javier, Tárraga, Lluís, Hendrix, Suzanne B., Ruiz, Agustín, Becker, James T., Landau, Susan M., Sotolongo Grau, Oscar, Sarasa, Manuel, Boada, Mercè, and Universitat Autònoma de Barcelona

Subjects
0301 basic medicine, cognition, Male, positron emission tomography, hippocampus, Neuropsychological Tests, Hippocampus, memory, Cognition, 0302 clinical medicine, Hippocampus (mythology), magnetic resonance imaging, Neuropsychological assessment, Composite material, Aged, 80 and over, Aniline Compounds, medicine.diagnostic_test, General Neuroscience, amyloid, Brain, General Medicine, Organ Size, Alzheimer's disease, 3. Good health, Psychiatry and Mental health, Clinical Psychology, Female, Psychology, Alzheimer’s disease, Research Article, Amyloid, Positron emission tomography, Prodromal Symptoms, Neuroimaging, 03 medical and health sciences, amnestic mild cognitive impairment, Magnetic resonance imaging, Memory, Alzheimer Disease, Fluorodeoxyglucose F18, mental disorders, medicine, Dementia, Humans, Cognitive Dysfunction, Survival analysis, Aged, medicine.disease, Survival Analysis, Thiazoles, 030104 developmental biology, Positron-Emission Tomography, Mental Recall, Amnestic mild cognitive impairment, Geriatrics and Gerontology, Radiopharmaceuticals, 030217 neurology & neurosurgery
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.

Published
2017

41. MRI PREDICTORS OF AMYLOID PATHOLOGY: RESULTS FROM THE EMIF-AD BIOMARKER DISCOVERY STUDY

Author

Kate, Mara ten, Redolfi, Alberto, Peira, Enrico, Bos, Isabelle, Vos, Stephanie J.B., Scheltens, Philip, Engelborghs, Sebastiaan, Frisoni, Giovanni B., Blin, Olivier, Richardson, Jill, Bordet, Régis, Wallin, Anders, Molinuevo, José Luis, Tsolaki, Magda, Verhey, Frans R.J., Popp, Julius, Martinez-Lage, Pablo, Vandenberghe, Rik, Baird, Alison L., Legido-Quigley, Cristina, Bertram, Lars, Zetterberg, Henrik, Lovestone, Simon, Streffer, Johannes, Novak, Gerald P., Revillard, Jérôme, Gordon, Mark Forrest, Xie, Zhiyong, Visser, Pieter Jelle, and Barkhof, Frederik

Published
2018
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42. European Prevention of Alzheimer's Dementia Registry: Recruitment and prescreening approach for a longitudinal cohort and prevention trials

Author

Vermunt, Lisa, Veal, Colin D., ter Meulen, Lea, Chrysostomou, Charalambos, van der Flier, Wiesje, Frisoni, Giovanni B., Guessous, Idris, Kivipelto, Miia, Marizzoni, Moira, Martinez-Lage, Pablo, Molinuevo, José Luis, Porteous, David, Ritchie, Karen, Scheltens, Philip, Ousset, Pierre-Jean, Ritchie, Craig W., Luscan, Gerald, Brookes, Anthony J., and Visser, Pieter Jelle

Published
2018
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43. Estrogen receptor alpha gene variants are associated with Alzheimer's disease

Author

Boada, Mercé, Antunez, Carmen, López-Arrieta, Jesús, Caruz, Antonio, Moreno-Rey, Concha, Ramírez-Lorca, Reposo, Morón, Francisco Jesús, Hernández, Isabel, Mauleón, Ana, Rosende-Roca, Maiteé, Martínez-Lage, Pablo, Marín, Juan, Tárraga, Lluis, Alegret, Montserrat, Pedrajas, José Rafael, Urda, Nuria, Royo, José Luis, Saez, María Eugenia, Gayán, Javier, González-Pérez, Antonio, Real, Luis Miguel, Ruiz, Agustín, and Galán, José Jorge

Published
2012
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44. Tau Protein is Associated with Longitudinal Memory Decline in Cognitively Healthy Subjects with Normal Alzheimer’s Disease Cerebrospinal Fluid Biomarker Levels

Author

Tort-Merino, Adrià, primary, Olives, Jaume, additional, León, María, additional, Peñaloza, Claudia, additional, Valech, Natalia, additional, Santos-Santos, Miguel A., additional, Càmara, Estela, additional, Grönholm-Nyman, Petra, additional, Martínez-Lage, Pablo, additional, Fortea, Juan, additional, Molinuevo, José L., additional, Sánchez-Valle, Raquel, additional, Laine, Matti, additional, Rodríguez-Fornells, Antoni, additional, and Rami, Lorena, additional

Published
2019
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45. Accelerated long‐term forgetting over three months in asymptomatic APOE ɛ4 carriers.

Author

Tort‐Merino, Adrià, Laine, Matti, Valech, Natalia, Olives, Jaume, León, María, Ecay‐Torres, Mirian, Estanga, Ainara, Martínez‐Lage, Pablo, Fortea, Juan, Sánchez‐Valle, Raquel, Rami, Lorena, and Rodríguez‐Fornells, Antoni

Subjects
ALZHEIMER'S disease, CEREBROSPINAL fluid, RECOLLECTION (Psychology)
Abstract

Accelerated long‐term forgetting (ALF) refers to a rapid loss of information over days or weeks despite normal acquisition/encoding. Notwithstanding its potential relevance as a presymptomatic marker of cognitive dysfunction, no study has addressed the relationship between ALF and Alzheimer's disease (AD) biomarkers. We examined ALF in APOE ɛ4 carriers versus noncarriers, and its relationships with AD cerebrospinal fluid (CSF) biomarkers. We found ALF over three months in APOE ɛ4 carriers (F(1,19) = 5.60; P < 0.05; Cohen's d = 1.08), and this performance was associated with abnormal levels of the CSF Aβ42/ptau ratio (r = −.614; P < 0.01). Our findings indicate that ALF is detectable in at‐risk individuals, and that there is a relationship between ALF and the pathophysiological processes underlying AD. [ABSTRACT FROM AUTHOR]

Published
2021
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46. Cortical microstructural changes along the Alzheimer's disease continuum

Author

Montal, Victor, primary, Vilaplana, Eduard, additional, Alcolea, Daniel, additional, Pegueroles, Jordi, additional, Pasternak, Ofer, additional, González‐Ortiz, Sofia, additional, Clarimón, Jordi, additional, Carmona‐Iragui, María, additional, Illán‐Gala, Ignacio, additional, Morenas‐Rodríguez, Estrella, additional, Ribosa‐Nogué, Roser, additional, Sala, Isabel, additional, Sánchez‐Saudinós, María‐Belén, additional, García‐Sebastian, Maite, additional, Villanúa, Jorge, additional, Izagirre, Andrea, additional, Estanga, Ainara, additional, Ecay‐Torres, Mirian, additional, Iriondo, Ane, additional, Clerigue, Montserrat, additional, Tainta, Mikel, additional, Pozueta, Ana, additional, González, Andrea, additional, Martínez‐Heras, Eloy, additional, Llufriu, Sara, additional, Blesa, Rafael, additional, Sanchez‐Juan, Pascual, additional, Martínez‐Lage, Pablo, additional, Lleó, Alberto, additional, and Fortea, Juan, additional

Published
2017
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48. Early Detection of Learning Difficulties when Confronted with Novel Information in Preclinical Alzheimer’s Disease Stage 1

Author

Tort-Merino, Adrià, primary, Valech, Natalia, additional, Peñaloza, Claudia, additional, Grönholm-Nyman, Petra, additional, León, María, additional, Olives, Jaume, additional, Estanga, Ainara, additional, Ecay-Torres, Mirian, additional, Fortea, Juan, additional, Martínez-Lage, Pablo, additional, Molinuevo, José L., additional, Laine, Matti, additional, Rodríguez-Fornells, Antoni, additional, and Rami, Lorena, additional

Published
2017
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49. Tau/α-synuclein ratio and inflammatory proteins in Parkinson's disease: An exploratory study

Author

Delgado-Alvarado, Manuel, primary, Gago, Belén, additional, Gorostidi, Ana, additional, Jiménez-Urbieta, Haritz, additional, Dacosta-Aguayo, Rosalía, additional, Navalpotro-Gómez, Irene, additional, Ruiz-Martínez, Javier, additional, Bergareche, Alberto, additional, Martí-Massó, José F., additional, Martínez-Lage, Pablo, additional, Izagirre, Andrea, additional, and Rodríguez-Oroz, María C., additional

Published
2017
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50. Cerebrospinal fluid mitochondrial DNA in the Alzheimer's disease continuum

Author

Cervera-Carles, Laura, primary, Alcolea, Daniel, additional, Estanga, Ainara, additional, Ecay-Torres, Mirian, additional, Izagirre, Andrea, additional, Clerigué, Montserrat, additional, García-Sebastián, Maite, additional, Villanúa, Jorge, additional, Escalas, Clàudia, additional, Blesa, Rafael, additional, Martínez-Lage, Pablo, additional, Lleó, Alberto, additional, Fortea, Juan, additional, and Clarimón, Jordi, additional

Published
2017
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