202 results on '"L. Tremolizzo"'
Search Results
2. New insights into the genetic etiology of Alzheimer's disease and related dementias
- Author
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Bellenguez, C. Küçükali, F. Jansen, I.E. Kleineidam, L. Moreno-Grau, S. Amin, N. Naj, A.C. Campos-Martin, R. Grenier-Boley, B. Andrade, V. Holmans, P.A. Boland, A. Damotte, V. van der Lee, S.J. Costa, M.R. Kuulasmaa, T. Yang, Q. de Rojas, I. Bis, J.C. Yaqub, A. Prokic, I. Chapuis, J. Ahmad, S. Giedraitis, V. Aarsland, D. Garcia-Gonzalez, P. Abdelnour, C. Alarcón-Martín, E. Alcolea, D. Alegret, M. Alvarez, I. Álvarez, V. Armstrong, N.J. Tsolaki, A. Antúnez, C. Appollonio, I. Arcaro, M. Archetti, S. Pastor, A.A. Arosio, B. Athanasiu, L. Bailly, H. Banaj, N. Baquero, M. Barral, S. Beiser, A. Pastor, A.B. Below, J.E. Benchek, P. Benussi, L. Berr, C. Besse, C. Bessi, V. Binetti, G. Bizarro, A. Blesa, R. Boada, M. Boerwinkle, E. Borroni, B. Boschi, S. Bossù, P. Bråthen, G. Bressler, J. Bresner, C. Brodaty, H. Brookes, K.J. Brusco, L.I. Buiza-Rueda, D. Bûrger, K. Burholt, V. Bush, W.S. Calero, M. Cantwell, L.B. Chene, G. Chung, J. Cuccaro, M.L. Carracedo, Á. Cecchetti, R. Cervera-Carles, L. Charbonnier, C. Chen, H.-H. Chillotti, C. Ciccone, S. Claassen, J.A.H.R. Clark, C. Conti, E. Corma-Gómez, A. Costantini, E. Custodero, C. Daian, D. Dalmasso, M.C. Daniele, A. Dardiotis, E. Dartigues, J.-F. de Deyn, P.P. de Paiva Lopes, K. de Witte, L.D. Debette, S. Deckert, J. Del Ser, T. Denning, N. DeStefano, A. Dichgans, M. Diehl-Schmid, J. Diez-Fairen, M. Rossi, P.D. Djurovic, S. Duron, E. Düzel, E. Dufouil, C. Eiriksdottir, G. Engelborghs, S. Escott-Price, V. Espinosa, A. Ewers, M. Faber, K.M. Fabrizio, T. Nielsen, S.F. Fardo, D.W. Farotti, L. Fenoglio, C. Fernández-Fuertes, M. Ferrari, R. Ferreira, C.B. Ferri, E. Fin, B. Fischer, P. Fladby, T. Fließbach, K. Fongang, B. Fornage, M. Fortea, J. Foroud, T.M. Fostinelli, S. Fox, N.C. Franco-Macías, E. Bullido, M.J. Frank-García, A. Froelich, L. Fulton-Howard, B. Galimberti, D. García-Alberca, J.M. García-González, P. Garcia-Madrona, S. Garcia-Ribas, G. Ghidoni, R. Giegling, I. Giorgio, G. Goate, A.M. Goldhardt, O. Gomez-Fonseca, D. González-Pérez, A. Graff, C. Grande, G. Green, E. Grimmer, T. Grünblatt, E. Grunin, M. Gudnason, V. Guetta-Baranes, T. Haapasalo, A. Hadjigeorgiou, G. Haines, J.L. Hamilton-Nelson, K.L. Hampel, H. Hanon, O. Hardy, J. Hartmann, A.M. Hausner, L. Harwood, J. Heilmann-Heimbach, S. Helisalmi, S. Heneka, M.T. Hernández, I. Herrmann, M.J. Hoffmann, P. Holmes, C. Holstege, H. Vilas, R.H. Hulsman, M. Humphrey, J. Biessels, G.J. Jian, X. Johansson, C. Jun, G.R. Kastumata, Y. Kauwe, J. Kehoe, P.G. Kilander, L. Ståhlbom, A.K. Kivipelto, M. Koivisto, A. Kornhuber, J. Kosmidis, M.H. Kukull, W.A. Kuksa, P.P. Kunkle, B.W. Kuzma, A.B. Lage, C. Laukka, E.J. Launer, L. Lauria, A. Lee, C.-Y. Lehtisalo, J. Lerch, O. Lleó, A. Longstreth, W., Jr Lopez, O. de Munain, A.L. Love, S. Löwemark, M. Luckcuck, L. Lunetta, K.L. Ma, Y. Macías, J. MacLeod, C.A. Maier, W. Mangialasche, F. Spallazzi, M. Marquié, M. Marshall, R. Martin, E.R. Montes, A.M. Rodríguez, C.M. Masullo, C. Mayeux, R. Mead, S. Mecocci, P. Medina, M. Meggy, A. Mehrabian, S. Mendoza, S. Menéndez-González, M. Mir, P. Moebus, S. Mol, M. Molina-Porcel, L. Montrreal, L. Morelli, L. Moreno, F. Morgan, K. Mosley, T. Nöthen, M.M. Muchnik, C. Mukherjee, S. Nacmias, B. Ngandu, T. Nicolas, G. Nordestgaard, B.G. Olaso, R. Orellana, A. Orsini, M. Ortega, G. Padovani, A. Paolo, C. Papenberg, G. Parnetti, L. Pasquier, F. Pastor, P. Peloso, G. Pérez-Cordón, A. Pérez-Tur, J. Pericard, P. Peters, O. Pijnenburg, Y.A.L. Pineda, J.A. Piñol-Ripoll, G. Pisanu, C. Polak, T. Popp, J. Posthuma, D. Priller, J. Puerta, R. Quenez, O. Quintela, I. Thomassen, J.Q. Rábano, A. Rainero, I. Rajabli, F. Ramakers, I. Real, L.M. Reinders, M.J.T. Reitz, C. Reyes-Dumeyer, D. Ridge, P. Riedel-Heller, S. Riederer, P. Roberto, N. Rodriguez-Rodriguez, E. Rongve, A. Allende, I.R. Rosende-Roca, M. Royo, J.L. Rubino, E. Rujescu, D. Sáez, M.E. Sakka, P. Saltvedt, I. Sanabria, Á. Sánchez-Arjona, M.B. Sanchez-Garcia, F. Juan, P.S. Sánchez-Valle, R. Sando, S.B. Sarnowski, C. Satizabal, C.L. Scamosci, M. Scarmeas, N. Scarpini, E. Scheltens, P. Scherbaum, N. Scherer, M. Schmid, M. Schneider, A. Schott, J.M. Selbæk, G. Seripa, D. Serrano, M. Sha, J. Shadrin, A.A. Skrobot, O. Slifer, S. Snijders, G.J.L. Soininen, H. Solfrizzi, V. Solomon, A. Song, Y. Sorbi, S. Sotolongo-Grau, O. Spalletta, G. Spottke, A. Squassina, A. Stordal, E. Tartan, J.P. Tárraga, L. Tesí, N. Thalamuthu, A. Thomas, T. Tosto, G. Traykov, L. Tremolizzo, L. Tybjærg-Hansen, A. Uitterlinden, A. Ullgren, A. Ulstein, I. Valero, S. Valladares, O. Broeckhoven, C.V. Vance, J. Vardarajan, B.N. van der Lugt, A. Dongen, J.V. van Rooij, J. van Swieten, J. Vandenberghe, R. Verhey, F. Vidal, J.-S. Vogelgsang, J. Vyhnalek, M. Wagner, M. Wallon, D. Wang, L.-S. Wang, R. Weinhold, L. Wiltfang, J. Windle, G. Woods, B. Yannakoulia, M. Zare, H. Zhao, Y. Zhang, X. Zhu, C. Zulaica, M. Farrer, L.A. Psaty, B.M. Ghanbari, M. Raj, T. Sachdev, P. Mather, K. Jessen, F. Ikram, M.A. de Mendonça, A. Hort, J. Tsolaki, M. Pericak-Vance, M.A. Amouyel, P. Williams, J. Frikke-Schmidt, R. Clarimon, J. Deleuze, J.-F. Rossi, G. Seshadri, S. Andreassen, O.A. Ingelsson, M. Hiltunen, M. Sleegers, K. Schellenberg, G.D. van Duijn, C.M. Sims, R. van der Flier, W.M. Ruiz, A. Ramirez, A. Lambert, J.-C. EADB GR@ACE DEGESCO EADI GERAD Demgene FinnGen ADGC CHARGE
- Abstract
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele. © 2022. The Author(s).
- Published
- 2022
3. Cerebrospinal fluid and serum HDL cholesterol efflux capacity is impaired in neurodegenerative disorders
- Author
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C. Marchi, M.P. Adorni, E. Conti, L. Tremolizzo, L. Calabresi, F. Bernini, and F. Zimetti
- Subjects
Cardiology and Cardiovascular Medicine - Published
- 2022
4. Lipoprotein metabolism in Alzheimer’s disease: CSF and plasma HDL characterization in an Italian cohort
- Author
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M. Turri, C. Pavanello, F. Gastoldi, E. Conti, D. Emide, A. Barbiroli, L. Tremolizzo, and L. Calabresi
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Cardiology and Cardiovascular Medicine - Published
- 2022
5. Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- Author
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de Rojas, I. Moreno-Grau, S. Tesi, N. Grenier-Boley, B. Andrade, V. Jansen, I.E. Pedersen, N.L. Stringa, N. Zettergren, A. Hernández, I. Montrreal, L. Antúnez, C. Antonell, A. Tankard, R.M. Bis, J.C. Sims, R. Bellenguez, C. Quintela, I. González-Perez, A. Calero, M. Franco-Macías, E. Macías, J. Blesa, R. Cervera-Carles, L. Menéndez-González, M. Frank-García, A. Royo, J.L. Moreno, F. Huerto Vilas, R. Baquero, M. Diez-Fairen, M. Lage, C. García-Madrona, S. García-González, P. Alarcón-Martín, E. Valero, S. Sotolongo-Grau, O. Ullgren, A. Naj, A.C. Lemstra, A.W. Benaque, A. Pérez-Cordón, A. Benussi, A. Rábano, A. Padovani, A. Squassina, A. de Mendonça, A. Arias Pastor, A. Kok, A.A.L. Meggy, A. Pastor, A.B. Espinosa, A. Corma-Gómez, A. Martín Montes, A. Sanabria, Á. DeStefano, A.L. Schneider, A. Haapasalo, A. Kinhult Ståhlbom, A. Tybjærg-Hansen, A. Hartmann, A.M. Spottke, A. Corbatón-Anchuelo, A. Rongve, A. Borroni, B. Arosio, B. Nacmias, B. Nordestgaard, B.G. Kunkle, B.W. Charbonnier, C. Abdelnour, C. Masullo, C. Martínez Rodríguez, C. Muñoz-Fernandez, C. Dufouil, C. Graff, C. Ferreira, C.B. Chillotti, C. Reynolds, C.A. Fenoglio, C. Van Broeckhoven, C. Clark, C. Pisanu, C. Satizabal, C.L. Holmes, C. Buiza-Rueda, D. Aarsland, D. Rujescu, D. Alcolea, D. Galimberti, D. Wallon, D. Seripa, D. Grünblatt, E. Dardiotis, E. Düzel, E. Scarpini, E. Conti, E. Rubino, E. Gelpi, E. Rodriguez-Rodriguez, E. Duron, E. Boerwinkle, E. Ferri, E. Tagliavini, F. Küçükali, F. Pasquier, F. Sanchez-Garcia, F. Mangialasche, F. Jessen, F. Nicolas, G. Selbæk, G. Ortega, G. Chêne, G. Hadjigeorgiou, G. Rossi, G. Spalletta, G. Giaccone, G. Grande, G. Binetti, G. Papenberg, G. Hampel, H. Bailly, H. Zetterberg, H. Soininen, H. Karlsson, I.K. Alvarez, I. Appollonio, I. Giegling, I. Skoog, I. Saltvedt, I. Rainero, I. Rosas Allende, I. Hort, J. Diehl-Schmid, J. Van Dongen, J. Vidal, J.-S. Lehtisalo, J. Wiltfang, J. Thomassen, J.Q. Kornhuber, J. Haines, J.L. Vogelgsang, J. Pineda, J.A. Fortea, J. Popp, J. Deckert, J. Buerger, K. Morgan, K. Fließbach, K. Sleegers, K. Molina-Porcel, L. Kilander, L. Weinhold, L. Farrer, L.A. Wang, L.-S. Kleineidam, L. Farotti, L. Parnetti, L. Tremolizzo, L. Hausner, L. Benussi, L. Froelich, L. Ikram, M.A. Deniz-Naranjo, M.C. Tsolaki, M. Rosende-Roca, M. Löwenmark, M. Hulsman, M. Spallazzi, M. Pericak-Vance, M.A. Esiri, M. Bernal Sánchez-Arjona, M. Dalmasso, M.C. Martínez-Larrad, M.T. Arcaro, M. Nöthen, M.M. Fernández-Fuertes, M. Dichgans, M. Ingelsson, M. Herrmann, M.J. Scherer, M. Vyhnalek, M. Kosmidis, M.H. Yannakoulia, M. Schmid, M. Ewers, M. Heneka, M.T. Wagner, M. Scamosci, M. Kivipelto, M. Hiltunen, M. Zulaica, M. Alegret, M. Fornage, M. Roberto, N. van Schoor, N.M. Seidu, N.M. Banaj, N. Armstrong, N.J. Scarmeas, N. Scherbaum, N. Goldhardt, O. Hanon, O. Peters, O. Skrobot, O.A. Quenez, O. Lerch, O. Bossù, P. Caffarra, P. Dionigi Rossi, P. Sakka, P. Hoffmann, P. Holmans, P.A. Fischer, P. Riederer, P. Yang, Q. Marshall, R. Kalaria, R.N. Mayeux, R. Vandenberghe, R. Cecchetti, R. Ghidoni, R. Frikke-Schmidt, R. Sorbi, S. Hägg, S. Engelborghs, S. Helisalmi, S. Botne Sando, S. Kern, S. Archetti, S. Boschi, S. Fostinelli, S. Gil, S. Mendoza, S. Mead, S. Ciccone, S. Djurovic, S. Heilmann-Heimbach, S. Riedel-Heller, S. Kuulasmaa, T. del Ser, T. Lebouvier, T. Polak, T. Ngandu, T. Grimmer, T. Bessi, V. Escott-Price, V. Giedraitis, V. Deramecourt, V. Maier, W. Jian, X. Pijnenburg, Y.A.L. Smith, A.D. Saenz, A. Bizzarro, A. Lauria, A. Vacca, A. Solomon, A. Anastasiou, A. Richardson, A. Boland, A. Koivisto, A. Daniele, A. Greco, A. Marianthi, A. McGuinness, B. Fin, B. Ferrari, C. Custodero, C. Ferrarese, C. Ingino, C. Mangone, C. Reyes Toso, C. Martínez, C. Cuesta, C. Muchnik, C. Joachim, C. Ortiz, C. Besse, C. Johansson, C. Zoia, C.P. Laske, C. Anastasiou, C. Palacio, D.L. Politis, D.G. Janowitz, D. Craig, D. Mann, D.M. Neary, D. Jürgen, D. Daian, D. Belezhanska, D. Kohler, E. Castaño, E.M. Koutsouraki, E. Chipi, E. De Roeck, E. Costantini, E. Vardy, E.R.L.C. Piras, F. Roveta, F. Piras, F. Prestia, F.A. Assogna, F. Salani, F. Sala, G. Lacidogna, G. Novack, G. Wilcock, G. Thonberg, H. Kölsch, H. Weber, H. Boecker, H. Etchepareborda, I. Piaceri, I. Tuomilehto, J. Lindström, J. Laczo, J. Johnston, J. Deleuze, J.-F. Harris, J. Schott, J.M. Priller, J. Bacha, J.I. Snowden, J. Lisso, J. Mihova, K.Y. Traykov, L. Morelli, L. Brusco, L.I. Rainer, M. Takalo, M. Bjerke, M. Del Zompo, M. Serpente, M. Sanchez Abalos, M. Rios, M. Peltonen, M. Herrman, M.J. Kosmidis, M.H. Kohler, M. Rojo, M. Jones, M. Orsini, M. Medel, N. Olivar, N. Fox, N.C. Salvadori, N. Hooper, N.M. Galeano, P. Solis, P. Bastiani, P. Mecocci, P. Passmore, P. Heun, R. Antikainen, R. Olaso, R. Perneczky, R. Germani, S. López-García, S. Love, S. Mehrabian, S. Bagnoli, S. Kochen, S. Andreoni, S. Teipel, S. Todd, S. Pickering-Brown, S. Natunen, T. Tegos, T. Laatikainen, T. Strandberg, T. Polvikoski, T.M. Matoska, V. Ciullo, V. Cores, V. Solfrizzi, V. Lisetti, V. Sevillano, Z. Abdelnour, C. Aguilera, N. Alarcon, E. Alegret, M. Benaque, A. Boada, M. Buendia, M. Cañabate, P. Carracedo, A. Corbatón-Anchuelo, A. Diego, S. Espinosa, A. Gailhajenet, A. Gil, S. Guitart, M. Hernández, I. Ibarria, M. Lafuente, A. Macias, J. Maroñas, O. Martín, E. Martínez, M.T. Marquié, M. Mauleón, A. Montrreal, L. Moreno-Grau, S. Moreno, M. Orellana, A. Ortega, G. Pancho, A. Pelejá, E. Pérez-Cordon, A. Pineda, J.A. Preckler, S. Quintela, I. Real, L.M. Rosende-Roca, M. Ruiz, A. Sáez, M.E. Sanabria, A. Serrano-Rios, M. Sotolongo-Grau, O. Tárraga, L. Valero, S. Vargas, L. Adarmes-Gómez, A.D. Alarcón-Martín, E. Alonso, M.D. Álvarez, I. Álvarez, V. Amer-Ferrer, G. Antequera, M. Antúnez, C. Baquero, M. Bernal, M. Blesa, R. Boada, M. Buiza-Rueda, D. Bullido, M.J. Burguera, J.A. Calero, M. Carrillo, F. Carrión-Claro, M. Casajeros, M.J. Clarimón, J. Cruz-Gamero, J.M. de Pancorbo, M.M. del Ser, T. Diez-Fairen, M. Escuela, R. Garrote-Espina, L. Fortea, J. Franco-Macías, E. Frank-García, A. García-Alberca, J.M. Garcia Madrona, S. Garcia-Ribas, G. Gómez-Garre, P. Hernández, I. Hevilla, S. Jesús, S. Labrador Espinosa, M.A. Lage, C. Legaz, A. Lleó, A. Lopez de Munain, A. López-García, S. Macias-García, D. Manzanares, S. Marín, M. Marín-Muñoz, J. Marín, T. Marquié, M. Martín Montes, A. Martínez, B. Martínez, C. Martínez, V. Martínez-Lage Álvarez, P. Medina, M. Mendioroz Iriarte, M. Mir, P. Molinuevo, J.L. Pastor, P. Pérez Tur, J. Periñán-Tocino, T. Pineda-Sanchez, R. Piñol-Ripoll, G. Rábano, A. Real de Asúa, D. Rodrigo, S. Rodríguez-Rodríguez, E. Royo, J.L. Ruiz, A. Sanchez del Valle Díaz, R. Sánchez-Juan, P. Sastre, I. Valero, S. Vicente, M.P. Vigo-Ortega, R. Vivancos, L. Macleod, C. McCracken, C. Brayne, C. Bresner, C. Grozeva, D. Bellou, E. Sommerville, E.W. Matthews, F. Leonenko, G. Menzies, G. Windle, G. Harwood, J. Phillips, J. Bennett, K. Luckuck, L. Clare, L. Woods, R. Saad, S. Burholt, V. Jansen, I.E. Rongve, A. Kehoe, P.G. Garcia-Ribas, G. Sánchez-Juan, P. Pastor, P. Pérez-Tur, J. Piñol-Ripoll, G. Lopez de Munain, A. García-Alberca, J.M. Bullido, M.J. Álvarez, V. Lleó, A. Real, L.M. Scheltens, P. Holstege, H. Marquié, M. Sáez, M.E. Carracedo, Á. Amouyel, P. Schellenberg, G.D. Williams, J. Seshadri, S. van Duijn, C.M. Mather, K.A. Sánchez-Valle, R. Serrano-Ríos, M. Orellana, A. Tárraga, L. Blennow, K. Huisman, M. Andreassen, O.A. Posthuma, D. Clarimón, J. Boada, M. van der Flier, W.M. Ramirez, A. Lambert, J.-C. van der Lee, S.J. Ruiz, A. EADB contributors The GR@ACE study group DEGESCO consortium IGAP (ADGC, CHARGE, EADI, GERAD) PGC-ALZ consortia
- Abstract
Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
- Published
- 2021
6. CLEARANCE OF BETA-AMYLOID OLIGOMERS BY PERIPHERAL MONOCYTES: FURTHER OBSERVATIONS REGARDING THE MODULATORY ROLE OF DONEPEZIL
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A. Karantzoulis, E. Conti, M. Slongo, V. Rodriguez-Menendez, M. Mauri, F. Da Re, A. Aliprandi, P. Basilico, A. Salmaggi, I. Appollonio, C. Ferrarese, L. Tremolizzo, Karantzoulis, A, Conti, E, Slongo, M, Rodriguez-Menendez, V, Mauri, M, Da Re, F, Aliprandi, A, Basilico, P, Salmaggi, A, Appollonio, I, Ferrarese, C, and Tremolizzo, L
- Subjects
MED/26 - NEUROLOGIA ,Donepezil, phagocytosis, beta-amyloid - Published
- 2020
7. LONGITUDINAL PATTERNS OF ATROPHY IN CLINICAL VARIANTS OF FRONTOTEMPORAL LOBAR DEGENERATION
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E. G. Spinelli, S. Basaia, C. Cividini, N. Riva, G. Magnani, F. Caso, P. Caroppo, S. Prioni, L. Tremolizzo, I. Appollonio, V. Silani, P. Carrera, M. Filippi, F. Agosta, Spinelli, E, Basaia, S, Cividini, C, Riva, N, Magnani, G, Caso, F, Caroppo, P, Prioni, S, Tremolizzo, L, Appollonio, I, Silani, V, Carrera, P, Filippi, M, and Agosta, F
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MED/26 - NEUROLOGIA ,brain MRI, frontotemporal lobar degeneration, atrophy - Published
- 2020
8. LATE-ONSET EPILEPSY WITH UNKNOWN ETIOLOGY: A PILOT STUDY ON NEUROPSYCHOLOGICAL PROFILE, CEREBROSPINAL FLUID BIOMARKERS, AND QUANTITATIVE EEG CHARACTERISTICS
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E. Nardi Cesarini, C. Babiloni, N. Salvadori, L. Farotti, C. Del Perci, M. Pascarelli, G. Noce, R. Lizio, F. DaRe, V. Isella, L. Tremolizzo, C. Calvello, M. Romoli, J. DiFrancesco, L. Parnetti, C. Costa, Nardi Cesarini, E, Babiloni, C, Salvadori, N, Farotti, L, Del Perci, C, Pascarelli, M, Noce, G, Lizio, R, Dare, F, Isella, V, Tremolizzo, L, Calvello, C, Romoli, M, Difrancesco, J, Parnetti, L, and Costa, C
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MED/26 - NEUROLOGIA ,epiilepsy, dementia, Alzheimer, biomarkers - Published
- 2020
9. BRAIN MRI SIGNATURES OF ATROPHY IN GENETIC FRONTOTEMPORAL LOBAR DEGENERATION
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F. Agosta, E. Spinelli, A. Ghirelli, N. Riva, S. Basaia, C. Cividini, G. Magnani, F. Caso, P. Caroppo, S. Prioni, L. Tremolizzo, I. Appollonio, V. Silani, P. Carrera, M. Filippi, Agosta, F, Spinelli, E, Ghirelli, A, Riva, N, Basaia, S, Cividini, C, Magnani, G, Caso, F, Caroppo, P, Prioni, S, Tremolizzo, L, Appollonio, I, Silani, V, Carrera, P, and Filippi, M
- Subjects
MED/26 - NEUROLOGIA ,brain MRI, frontotemporal lobar degeneration - Published
- 2020
10. LATE-ONSET EPILEPSY WITH UNKNOWN ETIOLOGY: A PILOT STUDY ON NEUROPSYCHOLOGICAL PROFILE, CEREBROSPINAL FLUID BIOMARKERS, AND QUANTITATIVE EEG CHARACTERISTICS
- Author
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Nardi Cesarini, E, Babiloni, C, Salvadori, N, Farotti, L, Del Perci, C, Pascarelli, M, Noce, G, Lizio, R, Dare, F, Isella, V, Tremolizzo, L, Calvello, C, Romoli, M, Difrancesco, J, Parnetti, L, Costa, C, E. Nardi Cesarini, C. Babiloni, N. Salvadori, L. Farotti, C. Del Perci, M. Pascarelli, G. Noce, R. Lizio, F. DaRe, V. Isella, L. Tremolizzo, C. Calvello, M. Romoli, J. DiFrancesco, L. Parnetti, C. Costa, Nardi Cesarini, E, Babiloni, C, Salvadori, N, Farotti, L, Del Perci, C, Pascarelli, M, Noce, G, Lizio, R, Dare, F, Isella, V, Tremolizzo, L, Calvello, C, Romoli, M, Difrancesco, J, Parnetti, L, Costa, C, E. Nardi Cesarini, C. Babiloni, N. Salvadori, L. Farotti, C. Del Perci, M. Pascarelli, G. Noce, R. Lizio, F. DaRe, V. Isella, L. Tremolizzo, C. Calvello, M. Romoli, J. DiFrancesco, L. Parnetti, and C. Costa
- Published
- 2020
11. LONGITUDINAL PATTERNS OF ATROPHY IN CLINICAL VARIANTS OF FRONTOTEMPORAL LOBAR DEGENERATION
- Author
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Spinelli, E, Basaia, S, Cividini, C, Riva, N, Magnani, G, Caso, F, Caroppo, P, Prioni, S, Tremolizzo, L, Appollonio, I, Silani, V, Carrera, P, Filippi, M, Agosta, F, E. G. Spinelli, S. Basaia, C. Cividini, N. Riva, G. Magnani, F. Caso, P. Caroppo, S. Prioni, L. Tremolizzo, I. Appollonio, V. Silani, P. Carrera, M. Filippi, F. Agosta, Spinelli, E, Basaia, S, Cividini, C, Riva, N, Magnani, G, Caso, F, Caroppo, P, Prioni, S, Tremolizzo, L, Appollonio, I, Silani, V, Carrera, P, Filippi, M, Agosta, F, E. G. Spinelli, S. Basaia, C. Cividini, N. Riva, G. Magnani, F. Caso, P. Caroppo, S. Prioni, L. Tremolizzo, I. Appollonio, V. Silani, P. Carrera, M. Filippi, and F. Agosta
- Published
- 2020
12. CLEARANCE OF BETA-AMYLOID OLIGOMERS BY PERIPHERAL MONOCYTES: FURTHER OBSERVATIONS REGARDING THE MODULATORY ROLE OF DONEPEZIL
- Author
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Karantzoulis, A, Conti, E, Slongo, M, Rodriguez-Menendez, V, Mauri, M, Da Re, F, Aliprandi, A, Basilico, P, Salmaggi, A, Appollonio, I, Ferrarese, C, Tremolizzo, L, A. Karantzoulis, E. Conti, M. Slongo, V. Rodriguez-Menendez, M. Mauri, F. Da Re, A. Aliprandi, P. Basilico, A. Salmaggi, I. Appollonio, C. Ferrarese, L. Tremolizzo, Karantzoulis, A, Conti, E, Slongo, M, Rodriguez-Menendez, V, Mauri, M, Da Re, F, Aliprandi, A, Basilico, P, Salmaggi, A, Appollonio, I, Ferrarese, C, Tremolizzo, L, A. Karantzoulis, E. Conti, M. Slongo, V. Rodriguez-Menendez, M. Mauri, F. Da Re, A. Aliprandi, P. Basilico, A. Salmaggi, I. Appollonio, C. Ferrarese, and L. Tremolizzo
- Published
- 2020
13. BRAIN MRI SIGNATURES OF ATROPHY IN GENETIC FRONTOTEMPORAL LOBAR DEGENERATION
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Agosta, F, Spinelli, E, Ghirelli, A, Riva, N, Basaia, S, Cividini, C, Magnani, G, Caso, F, Caroppo, P, Prioni, S, Tremolizzo, L, Appollonio, I, Silani, V, Carrera, P, Filippi, M, F. Agosta, E. Spinelli, A. Ghirelli, N. Riva, S. Basaia, C. Cividini, G. Magnani, F. Caso, P. Caroppo, S. Prioni, L. Tremolizzo, I. Appollonio, V. Silani, P. Carrera, M. Filippi, Agosta, F, Spinelli, E, Ghirelli, A, Riva, N, Basaia, S, Cividini, C, Magnani, G, Caso, F, Caroppo, P, Prioni, S, Tremolizzo, L, Appollonio, I, Silani, V, Carrera, P, Filippi, M, F. Agosta, E. Spinelli, A. Ghirelli, N. Riva, S. Basaia, C. Cividini, G. Magnani, F. Caso, P. Caroppo, S. Prioni, L. Tremolizzo, I. Appollonio, V. Silani, P. Carrera, and M. Filippi
- Published
- 2020
14. Modèle épigénétique chez la souris de la modulation pharmacologique de la vulnérabilité à la schizophrénie
- Author
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L. Tremolizzo
- Subjects
Behavioral analysis ,Psychiatry and Mental health ,Arts and Humanities (miscellaneous) ,Chemistry ,Neuronal metabolism ,Molecular biology ,Injections subcutaneous - Abstract
La reelin est une proteine qui pourrait etre liee a la vulnerabilite genetique a la schizophrenie. Elle joue un role specifi que dans le developpement cortical. Cette proteine, presente dans les terminaisons nerveuses des neurones gabaergiques, semble jouer un role regulateur au niveau des synapses glutamatergiques, en partie par l’intermediaire des recepteurs a l’integrine. Elle est localisee en particulier dans les neurones du cortex frontal pyramidal [5]. L’expression du ARN m de la reelin apparait diminuee dans les cerveaux de sujets schizophrenes en post-mortem, de meme que chez les bipolaires, mais pas chez les unipolaires, comparativement aux sujets controles [4]. Les mecanismes epigenetiques consistent en des modifi cations de l’expression des genes sans modifi cation de la sequence de l’ADN. Ces mecanismes se rapportent a des modifi cations covalentes de l’ADN et de la chromatine ; de telles modifi cations impliquent des remodelages structuraux de la chromatine d’ordre eleve, s’accompagnant de modifi cations de l’accessibilite des facteurs de transcription aux regions promotrices de genes specifi ques. La regulation epigenetique de l’expression des genes met en jeu des phenomenes de methylation des genes promoteurs, avec transformation de la cytosine en 5-methylcytosine. Les ilots CpG sont des regions chromosomiques riches en dinucleotides C-G, qui sont frequemment presentes dans les regions promotrices des genes, et qui sont caracterisees par un faible profi l de methylation. Une hypermethylation des ilots CpG induit une down-regulation transcriptionnelle du gene correspondant. Les mecanismes de regulation epigenetiques de l’expression des genes mettent egalement en jeu les histones : des modifi cations dynamiques de la conformation de la chromatine (transformation d’euchromatine en heterochromatine sous l’effet des demethylases [3]) et de l’accessibilite des facteurs de transcription dans les replis chromosomiques sont regules par des modifi cations des terminaisons des histones N-terminaux.
- Published
- 2007
15. Do outcome measures used in neurological clinical research realistically represent the needs and the expectations of patients and their care givers?
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C Motto, L Tremolizzo, E Susani, V Oppo, M Congedo, Angelo A. Bignamini, M Carlini, C Cusi, A Serafini, S Macone, P Candelaresi, M G Celani, K Nardi, Annalisa Sgoifo, Teresa Anna Cantisani, C Piersanti, M Cecconi, MC Bassi, S Cuzzubbo, V Piras, M Melis, D Guerra, and R Papetti
- Subjects
medicine.medical_specialty ,media_common.quotation_subject ,Alternative medicine ,Medicine (miscellaneous) ,Disease ,Bioinformatics ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,medicine ,Dementia ,Pharmacology (medical) ,030212 general & internal medicine ,media_common ,Selection bias ,business.industry ,030503 health policy & services ,medicine.disease ,Focus group ,Clinical research ,Systematic review ,Family medicine ,Poster Presentation ,0305 other medical science ,business - Abstract
Methods Stroke, dementia and epilepsy are the greater and most common disabling neurological diseases and were considered in this study. For each mentioned disease we will perform a Systematic reviews of all randomized clinical trials published in any language over the last 5 years with the aim of identifying and analyzing the outcome measures used in the evaluation of any kind of intervention. Fifteen Neurologists are filling out a single computerized form for each single trial assigned. The form has the following information: Characteristics of the trial with relevance on quality, Extent of variability in end points selected and their domains, Scales or techniques used to make the measurement, type of analysis applied and time of measurement, Presence of attrition bias in terms of fraction of patients reported by end points on the number enrolled in the study, Presence of outcome reporting bias in terms of end points declared and non-reported, end points not declared but reported, Source of funding. The valuation of patient and career needs and emotions will be performed with focus group discussions in a parallel section of the study.
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- 2015
16. A GABAergic cortical deficit dominates schizophrenia pathophysiology
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E, Costa, J M, Davis, E, Dong, D R, Grayson, A, Guidotti, L, Tremolizzo, and M, Veldic
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Cerebral Cortex ,Neurons ,Neuronal Plasticity ,Pyramidal Cells ,Phencyclidine ,Dendrites ,Receptors, GABA-A ,Receptors, N-Methyl-D-Aspartate ,Reelin Protein ,Hallucinogens ,Schizophrenia ,Animals ,Humans ,Excitatory Amino Acid Antagonists ,gamma-Aminobutyric Acid ,Antipsychotic Agents - Abstract
Several lines of evidence support the role of an epigenetic-induced GABAergic cortical dysfunction in schizophrenia psychopathology, which is probably dependent on an increase in the expression of DNA-methyltransferase-1 occurring selectively in GABAergic neurons. The key enzyme regulating GABA synthesis, termed glutamic acid decarboxylase 67 (GAD67) and the important neurodevelopmental protein called reelin are coexpressed in GABAergic neurons. Upon release, GABA and reelin bind to postsynaptic receptors located in dendrites, somata, or the axon initial segment of pyramidal neurons. Because GAD67 and reelin are downregulated in schizophrenia, it is suggested that schizophrenics may express GABAergic deficit-related alterations of pyramidal neuron function. A reduction of dendritic spines is a finding reported in the prefrontal cortex of schizophrenia patients. Because dendritic spines are innervated by glutamatergic axon terminals, very probably this reduction of dendritic spine expression is translated into a functional deficit of glutamatergic transmission. Plastic modifications of neuronal circuits are probably dependent on GABAergic transmitter tone, and it is likely that GABAergic dysfunction is at the root of synaptic plasticity deficits in schizophrenia. Thus, a possible avenue for the treatment of schizophrenia would be to address this GABAergic functional deficit using positive allosteric modulators of the action of GABA at GABAA receptors. Benzodiazepines (BZ) such as diazepam are effective in treating positive and negative symptoms of schizophrenia, but because they positively modulate GABAA receptors expressing alpha1 subunits, these BZs cause sedation and tolerance. In contrast, imidazenil, a full allosteric modulator of GABAA receptors expressing alpha5 subunits may reduce psychotic symptomatology without producing sedation. Hence, imidazenil should be appropriately studied as a prospective candidate for a pharmacological intervention in schizophrenia.
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- 2004
17. On scrapie interference and artificial prions
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L TREMOLIZZO
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General Medicine - Published
- 2004
18. Epigenetic modulation for reparative dentinogenesis?
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A. Senna, V. Rodriguez-Menendez, L. Tremolizzo, Tremolizzo, L, Senna, A, and RODRIGUEZ MENENDEZ, V
- Subjects
Valproate ,Extracellular Matrix Proteins ,Odontoblasts ,Cell Adhesion Molecules, Neuronal ,Serine Endopeptidases ,Reparative dentinogenesis ,Nerve Tissue Proteins ,Biology ,Dentin, Secondary ,Cell biology ,Epigenesis, Genetic ,dentinogenesis ,Mice ,Reelin Protein ,Dentinogenesis ,Animals ,Epigenetics ,General Dentistry - Published
- 2004
19. Increased glutamate in CSF and plasma of patients with HIV dementia
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M. G. Espey, A. S. Basile, R. K. Heaton, R. J. Ellis, A. Aliprandi, M. Longoni, L. Tremolizzo, and C. Ferrarese
- Subjects
Neurology (clinical) - Published
- 2002
20. Italian Frontotemporal Dementia Network (FTD Group-SINDEM): sharing clinical and diagnostic procedures in Frontotemporal Dementia in Italy
- Author
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Borroni B., Turrone R., Galimberti D., Nacmias B., Alberici A., Benussi A., Caffarra P., Caltagirone C., Cappa S. F., Frisoni G. B., Ghidoni R., Marra C., Padovani A., Rainero I., Scarpini E., Silani V., Sorbi S., Tagliavini F., Tremolizzo L., Bruni A. C., Agosta F., Alberoni M., Appollonio I., Arighi A., Avanzi S., Baglio F., Benussi L., Bianchetti A., Binetti G., Bonanni L., Bottacchi E., Bruno G., Canevelli M., Canu E., Cerami C., Chiari A., Conti M. Z., Costa A., Costa M., Cotelli M., Cotelli M. S., Cupidi C., Daniele A., D'Anna S., de Caro M. F., De Togni L., Dell'Osa M. T., Di Stefano F., Ferrarese C., Ferrari C., Filastro F., Floris G., Franceschi M., Gennuso M., Ghidoni E., Giordana M. T., Gragnaniello D., Grimaldi L., Lanari A., Le Pira F., Lombardi G., Lorusso S., Ludovico L., Luzzi S., Magnani G., Manfredi L. G., Marano P., Marcone A., Marrosu M. G., Martorana A., Mascia M. G., Masullo C., Mauri M., Mazzone A., Mela A., Merlo P., Micheli A., Milia A., Mina C., Montella P., Mura G., Murru M. R., Nemni R., Paci C., Pantieri R., Panza F., Parnetti L., Perini M., Pettenati C., Piccininni M., Piccoli T., Pilia G., Pinessi L., Piras M. R., Realmuto S., Ricca I., Rizzetti M. C., Rozzini L., Rubino E., Sambati L., Seripa D., Siano P., Sinforiani E., Sorrentino G., Specchio L. M., Stracciari A., Susani E., Talarico G., Tartaglione B., Tessitore A., Thomas A., Tiezzi A., Tiraboschi P., Tognoni G., Tondelli M., Trebbastoni A., Turla M., Ursini F., Valluzzi F., Vista M., Zannino G., Zanusso G., Piccoli, T, B. Borroni, R. Turrone, D. Galimberti, B. Nacmia, A. Alberici, A. Benussi, P. Caffarra, C. Caltagirone, S. F. Cappa, G. B. Frisoni, R. Ghidoni, C. Marra, A. Padovani, I. Rainero, E. Scarpini, V. Silani, S. Sorbi, F. Tagliavini, L. Tremolizzo, A. C. Bruni, The FTD Group-SINDEM, Borroni, B, Turrone, R, Galimberti, D, Nacmias, B, Alberici, A, Benussi, A, Caffarra, P, Caltagirone, C, Cappa, Sf, Frisoni, Gb, Ghidoni, R, Marra, C, Padovani, A, Rainero, I, Scarpini, E, Silani, V, Sorbi, S, Tagliavini, F, Tremolizzo, L, Bruni, Ac, The FTD, Group-SINDEM, Agosta, F, Cappa, S, Frisoni, G, Bruni, A, Alberoni, M, Appollonio, I, Arighi, A, Avanzi, S, Baglio, F, Benussi, L, Bianchetti, A, Binetti, G, Bonanni, L, Bottacchi, E, Bruno, G, Canevelli, M, Canu, E, Cerami, C, Chiari, A, Conti, M, Costa, A, Costa, M, Cotelli, M, Cupidi, C, Daniele, A, D'Anna, S, de Caro, M, De Togni, L, Dell'Osa, M, Di Stefano, F, Ferrarese, C, Ferrari, C, Filastro, F, Floris, G, Franceschi, M, Gennuso, M, Ghidoni, E, Giordana, M, Gragnaniello, D, Grimaldi, L, Lanari, A, Le Pira, F, Lombardi, G, Lorusso, S, Ludovico, L, Luzzi, S, Magnani, G, Manfredi, L, Marano, P, Marcone, A, Marrosu, M, Martorana, A, Mascia, M, Masullo, C, Mauri, M, Mazzone, A, Mela, A, Merlo, P, Micheli, A, Milia, A, Mina, C, Montella, P, Mura, G, Murru, M, Nemni, R, Paci, C, Pantieri, R, Panza, F, Parnetti, L, Perini, M, Pettenati, C, Piccininni, M, Pilia, G, Pinessi, L, Piras, M, Realmuto, S, Ricca, I, Rizzetti, M, Rozzini, L, Rubino, E, Sambati, L, Seripa, D, Siano, P, Sinforiani, E, Sorrentino, G, Specchio, L, Stracciari, A, Susani, E, Talarico, G, Tartaglione, B, Tessitore, A, Thomas, A, Tiezzi, A, Tiraboschi, P, Tognoni, G, Tondelli, M, Trebbastoni, A, Turla, M, Ursini, F, Valluzzi, F, Vista, M, Zannino, G, and Zanusso, G
- Subjects
Counseling ,Male ,medicine.medical_specialty ,Neurology ,Network ,Frontotemporal dementia ,Frontotemporal lobar degeneration ,Genetics ,Survey ,Aged ,Aged, 80 and over ,Caregivers ,Female ,Frontotemporal Dementia ,Humans ,Italy ,Prevalence ,Community Networks ,Information Dissemination ,Medicine (all) ,2708 ,Neurology (clinical) ,Psychiatry and Mental Health ,Dermatology ,ddc:616.89 ,Caregivers/psychology ,Epidemiology ,mental disorders ,medicine ,80 and over ,Dementia ,Disease management (health) ,Psychiatry ,MED/26 - NEUROLOGIA ,Italian network ,FRONTO Temporal dementia ,business.industry ,Frontotemporal dementia, Frontotemporal lobar degeneration, Network, Survey, Genetics, Counseling ,General Medicine ,Frontotemporal Dementia/diagnosis/epidemiology ,medicine.disease ,Clinical trial ,Settore MED/26 - Neurologia ,Neurosurgery ,business - Abstract
In the prospect of improved disease management and future clinical trials in Frontotemporal Dementia, it is desirable to share common diagnostic procedures. To this aim, the Italian FTD Network, under the aegis of the Italian Neurological Society for Dementia, has been established. Currently, 85 Italian Centers involved in dementia care are part of the network. Each Center completed a questionnaire on the local clinical procedures, focused on (1) clinical assessment, (2) use of neuroimaging and genetics; (3) support for patients and caregivers; (4) an opinion about the prevalence of FTD. The analyses of the results documented a comprehensive clinical and instrumental approach to FTD patients and their caregivers in Italy, with about 1,000 newly diagnosed cases per year and 2,500 patients currently followed by the participating Centers. In analogy to other European FTD consortia, future aims will be devoted to collect data on epidemiology of FTD and its subtypes and to provide harmonization of procedures among Centers.
- Published
- 2014
21. An unusual stroke chameleon: acute isolated sialorrhea.
- Author
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Tremolizzo L, Funelli E, Mattavelli D, Benzoni C, and Appollonio I
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- Humans, Male, Female, Middle Aged, Sialorrhea etiology, Sialorrhea diagnosis, Stroke complications, Stroke diagnostic imaging, Stroke diagnosis
- Published
- 2024
- Full Text
- View/download PDF
22. Clinical and neuroanatomical characterization of the semantic behavioral variant of frontotemporal dementia in a multicenter Italian cohort.
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Ghirelli A, Spinelli EG, Canu E, Basaia S, Castelnovo V, Cecchetti G, Sibilla E, Domi T, Magnani G, Caso F, Caroppo P, Prioni S, Villa C, Rossi G, Tremolizzo L, Appollonio I, Verde F, Ticozzi N, Silani V, Filippi M, and Agosta F
- Subjects
- Humans, Female, Italy, Male, Middle Aged, Aged, Temporal Lobe pathology, Temporal Lobe diagnostic imaging, Cohort Studies, Neuropsychological Tests, Aphasia, Primary Progressive pathology, Aphasia, Primary Progressive diagnostic imaging, Retrospective Studies, Gray Matter pathology, Gray Matter diagnostic imaging, Frontotemporal Dementia pathology, Frontotemporal Dementia diagnostic imaging, Frontotemporal Dementia physiopathology, Magnetic Resonance Imaging, Atrophy pathology
- Abstract
Background: Semantic behavioral variant frontotemporal dementia (sbvFTD) is a neurodegenerative condition presenting with specific behavioral and semantic derangements and predominant atrophy of the right anterior temporal lobe (ATL). The objective was to evaluate clinical, neuropsychological, neuroimaging, and genetic features of an Italian sbvFTD cohort, defined according to recently proposed guidelines, compared to semantic variant primary progressive aphasia (svPPA) and behavioral variant FTD (bvFTD) patients., Methods: Fifteen sbvFTD, sixty-three bvFTD, and twenty-five svPPA patients and forty controls were enrolled. Patients underwent clinical, cognitive evaluations, and brain MRI. Symptoms of bvFTD patients between onset and first visit were retrospectively recorded and classified as early and late. Grey matter atrophy was investigated using voxel-based morphometry., Results: sbvFTD experienced early criteria-specific symptoms: world, object and person-specific semantic loss (67%), complex compulsions and rigid thought (60%). Sequentially, more behavioral symptoms emerged (apathy/inertia, loss of empathy) along with non-criteria-specific symptoms (anxiety, suspiciousness). sbvFTD showed sparing of attentive/executive functions, especially compared to bvFTD and better language functions compared to svPPA. All sbvFTD patients failed at the famous face recognition test and more than 80% failed in understanding written metaphors and humor. At MRI, sbvFTD had predominant right ATL atrophy, almost specular to svPPA. Three sbvFTD patients presented pathogenic genetic variants., Conclusion: We replicated the application of sbvFTD diagnostic guidelines in an independent Italian cohort, demonstrating that the presence of person-specific semantic knowledge loss and mental rigidity, along with preserved executive functions and a predominant right ATL atrophy with sparing of frontal lobes, should prompt a diagnosis of sbvFTD., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
23. Clinical and neuroimaging characterization of the first frontotemporal dementia family carrying the MAPT p.K298E mutation.
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Pozzi FE, Aprea V, Giovannelli G, Lattuada F, Crivellaro C, Bertola F, Castelnovo V, Canu E, Filippi M, Appollonio I, Ferrarese C, Agosta F, and Tremolizzo L
- Subjects
- Humans, Male, Middle Aged, Magnetic Resonance Imaging, Positron-Emission Tomography, Pedigree, Female, Genetic Association Studies, Brain diagnostic imaging, Brain pathology, Phenotype, Frontotemporal Dementia genetics, Frontotemporal Dementia diagnostic imaging, Frontotemporal Dementia pathology, tau Proteins genetics, Mutation genetics, Neuroimaging
- Abstract
We present an in-depth clinical and neuroimaging analysis of a family carrying the MAPT K298E mutation associated with frontotemporal dementia (FTD). Initial identification of this mutation in a single clinical case led to a comprehensive investigation involving four affected siblings allowing to elucidate the mutation's phenotypic expression.A 60-year-old male presented with significant behavioral changes and progressed rapidly, exhibiting speech difficulties and cognitive decline. Neuroimaging via FDG-PET revealed asymmetrical frontotemporal hypometabolism. Three siblings subsequently showed varied but consistent clinical manifestations, including abnormal behavior, speech impairments, memory deficits, and motor symptoms correlating with asymmetric frontotemporal atrophy observed in MRI scans.Based on the genotype-phenotype correlation, we propose that the p.K298E mutation results in early-onset behavioral variant FTD, accompanied by a various constellation of speech and motor impairment.This detailed characterization expands the understanding of the p.K298E mutation's clinical and neuroimaging features, underlining its role in the pathogenesis of FTD. Further research is crucial to comprehensively delineate the clinical and epidemiological implications of the MAPT p.K298E mutation., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
24. Corticosteroid treatment for acute hydrocephalus in neurosarcoidosis: a case report.
- Author
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Schilke ED, Remoli G, Cutellé C, Balducci C, Cereda D, Fusco ML, Tremolizzo L, Ferrarese C, Appollonio I, and Frigo M
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- Humans, Male, Adult, Adrenal Cortex Hormones therapeutic use, Seizures complications, Central Nervous System Diseases complications, Central Nervous System Diseases drug therapy, Central Nervous System Diseases diagnosis, Hydrocephalus complications, Hydrocephalus drug therapy, Sarcoidosis complications, Sarcoidosis drug therapy, Sarcoidosis diagnosis
- Abstract
Background: Neurosarcoidosis occurs symptomatically in 5-10% of patients with sarcoidosis, and hydrocephalus is a rare complication of neurosarcoidosis, with either acute or subacute onset and presenting symptoms related to increased intracranial pressure. It represents a potentially fatal manifestation with a mortality rate of 22% (increased to 75% in case of coexistence of seizures) that requires a prompt initiation of treatment. High-dose intravenous corticosteroid treatment and neurosurgical treatment must be considered in all cases of neurosarcoidosis hydrocephalus., Case Presentation: Here we present a case of hydrocephalus in neurosarcoidosis, complicated by generalized seizures, in a 29-year-old Caucasian male patient treated with medical treatment only, with optimal response., Conclusion: Since neurosurgery treatment can lead to severe complications, this case report underlines the possibility to undergo only medical treatment in selected cases. Further studies are needed to stratify patients and better identify those eligible for only medical approach., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
25. Brain Health and Cognition in Older Adults: Roadmap and Milestones towards the Implementation of Preventive Strategies.
- Author
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Pozzi FE, Remoli G, Tremolizzo L, Appollonio I, Ferrarese C, and Cuffaro L
- Abstract
In this narrative review, we delve into the evolving concept of brain health, as recognized by the WHO, focusing on its intersection with cognitive decline. We emphasize the imperative need for preventive strategies, particularly in older adults. We describe the target population that might benefit the most from risk-based approaches-namely, people with subjective cognitive decline. Additionally, we consider universal prevention in cognitively unimpaired middle-aged and older adults. Delving into multidomain personalized preventive strategies, we report on empirical evidence surrounding modifiable risk factors and interventions crucial in mitigating cognitive decline. Next, we highlight the emergence of brain health services (BHS). We explain their proposed role in risk assessment, risk communication, and tailored interventions to reduce the risk of dementia. Commenting on ongoing BHS pilot experiences, we present the inception and framework of our own BHS in Monza, Italy, outlining its operational structure and care pathways. We emphasize the need for global collaboration and intensified research efforts to address the intricate determinants of brain health and their potential impact on healthcare systems worldwide.
- Published
- 2024
- Full Text
- View/download PDF
26. Neuropathological hints from CSF and serum biomarkers in corticobasal syndrome (CBS): a systematic review.
- Author
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Remoli G, Schilke ED, Magi A, Ancidoni A, Negro G, Da Re F, Frigo M, Giordano M, Vanacore N, Canevelli M, Ferrarese C, Tremolizzo L, and Appollonio I
- Abstract
Corticobasal syndrome (CBS) is a clinical syndrome determined by various underlying neurodegenerative disorders requiring a pathological assessment for a definitive diagnosis. A literature review was performed following the methodology described in the Cochrane Handbook for Systematic Reviews to investigate the additional value of traditional and cutting-edge cerebrospinal fluid (CSF) and serum/plasma biomarkers in profiling CBS. Four databases were screened applying predefined inclusion criteria: (1) recruiting patients with CBS; (2) analyzing CSF/plasma biomarkers in CBS. The review highlights the potential role of the association of fluid biomarkers in diagnostic workup of CBS, since they may contribute to a more accurate diagnosis and patient selection for future disease-modifying agent; for example, future trial designs should consider baseline CSF Neurofilament Light Chains (NfL) or progranulin dosage to stratify treatment arms according to neuropathological substrates, and serum NfL dosage might be used to monitor the evolution of CBS. In this scenario, prospective cohort studies, starting with neurological examination and neuropsychological tests, should be considered to assess the correlations of clinical profiles and various biomarkers., (© 2024. The Author(s).)
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- 2024
- Full Text
- View/download PDF
27. BPSDiary study protocol: a multi-center randomized controlled trial to compare the efficacy of a BPSD diary vs. standard care in reducing caregiver's burden.
- Author
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Pozzi FE, Calì L, D'Antonio F, Altomare AI, Sepe Monti M, Panigutti M, Di Crosta A, Palumbo R, Bonanni L, Carlucci V, Bussè C, Cagning A, Urso D, Vilella D, Logroscino G, Alberoni M, Bellinvia A, Farina E, de Rino F, Gavazzi A, Zuffi M, Bruno G, Bessi V, Cotta Ramusino M, Perini G, Costa A, Ferrarese C, Appollonio I, and Tremolizzo L
- Abstract
Behavioral and Psychological Symptoms of Dementia (BPSD) are a heterogeneous set of psychological and behavioral abnormalities seen in persons with dementia (PwD), significantly impacting their quality of life and that of their caregivers. Current assessment tools, such as the Neuropsychiatric Inventory (NPI), are limited by recall bias and lack of direct observation. This study aims to overcome this limitation by making caregiver reports more objective through the use of a novel instrument, referred to as the BPSDiary. This randomized controlled trial will involve 300 caregiver-PwD dyads. The objective is to evaluate whether the use of the BPSDiary could significantly reduce caregiver burden, assessed using the Zarit Burden Interview (ZBI), compared to usual care. The study will include adult PwD, caregivers living with or close to the patient, and BPSD related to the HIDA (hyperactivity, impulsivity, irritability, disinhibition, aggression, agitation) domain. Caregivers randomized to the intervention arm will use the BPSDiary to record specific BPSD, including insomnia, agitation/anxiety, aggression, purposeless motor behavior, and delusions/hallucinations, registering time of onset, severity, and potential triggers. The primary outcome will be the change in ZBI scores at 3 months, with secondary outcomes including changes in NPI scores, olanzapine equivalents, NPI-distress scores related to specific BPSD domains, and caregiver and physician satisfaction. The study will be conducted in 9 Italian centers, representing diverse geographic and sociocultural contexts. While potential limitations include the relatively short observation period and the focus on specific BPSD disturbances, the BPSDiary could provide physicians with objective data to tailor appropriate non-pharmacological and pharmacological interventions. Additionally, it may empower caregivers by encouraging reflection on BPSD triggers, with the potential to improve the quality of life for both PwD and their caregivers., Trial Registry: NCT05977855., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Pozzi, Calì, D'Antonio, Altomare, Sepe Monti, Panigutti, Di Crosta, Palumbo, Bonanni, Carlucci, Bussè, Cagning, Urso, Vilella, Logroscino, Alberoni, Bellinvia, Farina, de Rino, Gavazzi, Zuffi, Bruno, Bessi, Cotta Ramusino, Perini, Costa, Ferrarese, Appollonio and Tremolizzo.)
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- 2023
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28. Multiancestry analysis of the HLA locus in Alzheimer's and Parkinson's diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes.
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Le Guen Y, Luo G, Ambati A, Damotte V, Jansen I, Yu E, Nicolas A, de Rojas I, Peixoto Leal T, Miyashita A, Bellenguez C, Lian MM, Parveen K, Morizono T, Park H, Grenier-Boley B, Naito T, Küçükali F, Talyansky SD, Yogeshwar SM, Sempere V, Satake W, Alvarez V, Arosio B, Belloy ME, Benussi L, Boland A, Borroni B, Bullido MJ, Caffarra P, Clarimon J, Daniele A, Darling D, Debette S, Deleuze JF, Dichgans M, Dufouil C, During E, Düzel E, Galimberti D, Garcia-Ribas G, García-Alberca JM, García-González P, Giedraitis V, Goldhardt O, Graff C, Grünblatt E, Hanon O, Hausner L, Heilmann-Heimbach S, Holstege H, Hort J, Jung YJ, Jürgen D, Kern S, Kuulasmaa T, Lee KH, Lin L, Masullo C, Mecocci P, Mehrabian S, de Mendonça A, Boada M, Mir P, Moebus S, Moreno F, Nacmias B, Nicolas G, Niida S, Nordestgaard BG, Papenberg G, Papma J, Parnetti L, Pasquier F, Pastor P, Peters O, Pijnenburg YAL, Piñol-Ripoll G, Popp J, Porcel LM, Puerta R, Pérez-Tur J, Rainero I, Ramakers I, Real LM, Riedel-Heller S, Rodriguez-Rodriguez E, Ross OA, Royo LJ, Rujescu D, Scarmeas N, Scheltens P, Scherbaum N, Schneider A, Seripa D, Skoog I, Solfrizzi V, Spalletta G, Squassina A, van Swieten J, Sánchez-Valle R, Tan EK, Tegos T, Teunissen C, Thomassen JQ, Tremolizzo L, Vyhnalek M, Verhey F, Waern M, Wiltfang J, Zhang J, Zetterberg H, Blennow K, He Z, Williams J, Amouyel P, Jessen F, Kehoe PG, Andreassen OA, Van Duin C, Tsolaki M, Sánchez-Juan P, Frikke-Schmidt R, Sleegers K, Toda T, Zettergren A, Ingelsson M, Okada Y, Rossi G, Hiltunen M, Gim J, Ozaki K, Sims R, Foo JN, van der Flier W, Ikeuchi T, Ramirez A, Mata I, Ruiz A, Gan-Or Z, Lambert JC, Greicius MD, and Mignot E
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- Humans, Histocompatibility Antigens, HLA Antigens, Alzheimer Disease genetics, HLA-DRB1 Chains genetics, Parkinson Disease genetics
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Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's disease (PD) and Alzheimer's disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1 *04 subtypes best accounted for the association, strongest with HLA-DRB1 *04:04 and HLA-DRB1 *04:07, and intermediary with HLA-DRB1 *04:01 and HLA-DRB1 *04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1 *04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1 *04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.
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- 2023
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29. Equating norms between the ALS Cognitive Behavioral Screen (ALS-CBS™) and the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) in non-demented ALS patients.
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Aiello EN, Solca F, Greco LC, Torre S, Carelli L, Morelli C, Doretti A, Colombo E, Messina S, Pain D, Radici A, Lizio A, Casiraghi J, Cerri F, Woolley S, Murphy J, Tremolizzo L, Appollonio I, Verde F, Sansone VA, Lunetta C, Silani V, Ticozzi N, and Poletti B
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- Humans, Retrospective Studies, Cross-Sectional Studies, Neuropsychological Tests, Cognition, Cognition Disorders psychology, Amyotrophic Lateral Sclerosis complications, Amyotrophic Lateral Sclerosis diagnosis, Amyotrophic Lateral Sclerosis genetics
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Background: The present study aimed at deriving equating norms to estimate scores on the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) based on those on the ALS Cognitive Behavioral Screen (ALS-CBS™) in an Italian cohort of non-demented ALS patients., Methods: ALS-CBS™ and ECAS scores of 293 ALS patients without frontotemporal dementia were retrospectively retrieved. Concurrent validity of the ALS-CBS™ towards the ECAS was tested by covarying for demographics, disease duration and severity, presence of C9orf72 hexanucleotide repeat expansion and behavioural features. A linear-smoothing equipercentile equating (LSEE) model was employed to derive ALS-CBS™-to-ECAS cross-walks. Gaps in LSEE-based estimation were managed via a linear regression-based equating approach. Equivalence between empirical and derived ECAS scores was tested via a two-one-sided test (TOST) procedure for the dependent sample., Results: The ALS-CBS™ predicted the ECAS (β = 0.75), accounting for the vast majority of its variance (60% out of an R
2 = 0.71). Consistently, a strong, one-to-one linear association between ALS-CBS™ and ECAS scores was detected (r = 0.84; R2 = 0.73). The LSEE was able to estimate conversions for the full range of the ALS-CBS™, except for raw scores equal to 1 and 6 - for whom a linear equating-based equation was derived. Empirical ECAS scores were equivalent to those derived with both methods., Discussion: Italian practitioners and researchers have been herewith provided with valid, straightforward cross-walks to estimate the ECAS based on ALS-CBS™ scores in non-demented ALS patients. Conversions herewith provided will help avoid cross-sectional/longitudinal inconsistencies in test adoption within research, and possibly clinical, settings., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)- Published
- 2023
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30. Assessing behavioral and psychological symptoms of dementia: a comprehensive review of current options and future perspectives.
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Pozzi FE, Calì L, Ferrarese C, Appollonio I, and Tremolizzo L
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The behavioral and psychological symptoms of dementia (BPSD) are a heterogeneous set of challenging disturbances of behavior, mood, perception, and thought that occur in almost all patients with dementia. A huge number of instruments have been developed to assess BPSD in different populations and settings. Although some of these tools are more widely used than others, no single instrument can be considered completely satisfactory, and each of these tools has its advantages and disadvantages. In this narrative review, we have provided a comprehensive overview of the characteristics of a large number of such instruments, addressing their applicability, strengths, and limitations. These depend on the setting, the expertise required, and the people involved, and all these factors need to be taken into account when choosing the most suitable scale or tool. We have also briefly discussed the use of objective biomarkers of BPSD. Finally, we have attempted to provide indications for future research in the field and suggest the ideal characteristics of a possible new tool, which should be short, easy to understand and use, and treatment oriented, providing clinicians with data such as frequency, severity, and triggers of behaviors and enabling them to find appropriate strategies to effectively tackle BPSD., Competing Interests: FP, CF, IA, and LT declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pozzi, Calì, Ferrarese, Appollonio and Tremolizzo.)
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- 2023
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31. Editorial: Strategies to fight exercise intolerance in neuromuscular disorders, volume II.
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Lanfranconi F, Tremolizzo L, Marzorati M, and D'Antona G
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Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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- 2023
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32. Functional Connectivity From Disease Epicenters in Frontotemporal Dementia.
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Agosta F, Spinelli EG, Basaia S, Cividini C, Falbo F, Pavone C, Riva N, Canu E, Castelnovo V, Magnani G, Caso F, Caroppo P, Prioni S, Villa C, Tremolizzo L, Appollonio I, Silani V, Josephs KA, Whitwell J, and Filippi M
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- Humans, Magnetic Resonance Imaging, Atrophy, Frontotemporal Dementia diagnostic imaging, Frontotemporal Dementia pathology, Pick Disease of the Brain, Primary Progressive Nonfluent Aphasia, Aphasia, Primary Progressive pathology
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Background and Objectives: MRI connectomics is an ideal tool to test a network-based model of pathologic propagation from a disease epicenter in neurodegenerative disorders. In this study, we used a novel graph theory-based MRI paradigm to explore functional connectivity reorganization, discerning between direct and indirect connections from disease epicenters, and its relationship with neurodegeneration across clinical presentations of the frontotemporal dementia (FTD) spectrum, including behavioral variant of FTD (bvFTD), nonfluent variant of primary progressive aphasia (nfvPPA), and semantic variant of primary progressive aphasia (svPPA)., Methods: In this observational cross-sectional study, disease epicenters were defined as the peaks of atrophy of a cohort of patients with high confidence of frontotemporal lobar degeneration pathology (Mayo Clinic). These were used as seed regions for stepwise functional connectivity (SFC) analyses in an independent (Milan) set of patients with FTD to assess connectivity in regions directly and indirectly connected to the epicenters. Correlations between SFC architecture in healthy conditions and atrophy patterns in patients with FTD were also tested., Results: As defined by comparing the 42 Mayo Clinic patients with 15 controls, disease epicenters were the left anterior insula for bvFTD, left supplementary motor area for nfvPPA, and left inferior temporal gyrus (ITG) for svPPA. Compared with 94 age-matched controls, patients with bvFTD (n = 64) and nfvPPA (n = 34) of the Milan cohort showed widespread decreased SFC in bilateral cortical regions with direct/indirect connections with epicenters and increased SFC either in directly connected regions, physically close to the respective seed region, or in more distant cortical/cerebellar areas with indirect connections. Across all link steps, svPPA (n = 36) showed SFC decrease mostly within the temporal lobes, with co-occurrent SFC increase in cerebellar regions at indirect link steps. The average stepwise topological distance from the left ITG in a reference group of 50 young healthy controls correlated with regional gray matter volume in svPPA, consistent with network-based degeneration., Discussion: Our findings demonstrate that each FTD syndrome is associated with a characteristic interplay of decreased and increased functional connectivity with the disease epicenter, affecting both direct and indirect connections. SFC revealed novel insights regarding the topology of functional disconnection across FTD syndromes, holding the promise to be used to model disease progression in future longitudinal studies., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)
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- 2023
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33. Plasma and cerebrospinal fluid cholesterol esterification is hampered in Alzheimer's disease.
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Turri M, Conti E, Pavanello C, Gastoldi F, Palumbo M, Bernini F, Aprea V, Re F, Barbiroli A, Emide D, Galimberti D, Tremolizzo L, Zimetti F, and Calabresi L
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- Humans, Esterification, High-Density Lipoproteins, Pre-beta, Cholesterol, Biomarkers, Alzheimer Disease cerebrospinal fluid
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Objective: The purpose of this study was to evaluate cholesterol esterification and HDL subclasses in plasma and cerebrospinal fluid (CSF) of Alzheimer's disease (AD) patients., Methods: The study enrolled 70 AD patients and 74 cognitively normal controls comparable for age and sex. Lipoprotein profile, cholesterol esterification, and cholesterol efflux capacity (CEC) were evaluated in plasma and CSF., Results: AD patients have normal plasma lipids but significantly reduced unesterified cholesterol and unesterified/total cholesterol ratio. Lecithin:cholesterol acyltransferase (LCAT) activity and cholesterol esterification rate (CER), two measures of the efficiency of the esterification process, were reduced by 29% and 16%, respectively, in the plasma of AD patients. Plasma HDL subclass distribution in AD patients was comparable to that of controls but the content of small discoidal preβ-HDL particles was significantly reduced. In agreement with the reduced preβ-HDL particles, cholesterol efflux capacity mediated by the transporters ABCA1 and ABCG1 was reduced in AD patients' plasma. The CSF unesterified to total cholesterol ratio was increased in AD patients, and CSF CER and CEC from astrocytes were significantly reduced in AD patients. In the AD group, a significant positive correlation was observed between plasma unesterified cholesterol and unesterified/total cholesterol ratio with Aβ
1-42 CSF content., Conclusion: Taken together our data indicate that cholesterol esterification is hampered in plasma and CSF of AD patients and that plasma cholesterol esterification biomarkers (unesterified cholesterol and unesterified/total cholesterol ratio) are significantly associated to disease biomarkers (i.e., CSF Aβ1-42 )., (© 2023. The Author(s).)- Published
- 2023
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34. Genetic Associations Between Modifiable Risk Factors and Alzheimer Disease.
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Luo J, Thomassen JQ, Bellenguez C, Grenier-Boley B, de Rojas I, Castillo A, Parveen K, Küçükali F, Nicolas A, Peters O, Schneider A, Dichgans M, Rujescu D, Scherbaum N, Jürgen D, Riedel-Heller S, Hausner L, Porcel LM, Düzel E, Grimmer T, Wiltfang J, Heilmann-Heimbach S, Moebus S, Tegos T, Scarmeas N, Clarimon J, Moreno F, Pérez-Tur J, Bullido MJ, Pastor P, Sánchez-Valle R, Álvarez V, Boada M, García-González P, Puerta R, Mir P, Real LM, Piñol-Ripoll G, García-Alberca JM, Royo JL, Rodriguez-Rodriguez E, Soininen H, Kuulasmaa T, de Mendonça A, Mehrabian S, Hort J, Vyhnalek M, van der Lee S, Graff C, Papenberg G, Giedraitis V, Boland A, Bacq-Daian D, Deleuze JF, Nicolas G, Dufouil C, Pasquier F, Hanon O, Debette S, Grünblatt E, Popp J, Benussi L, Galimberti D, Arosio B, Mecocci P, Solfrizzi V, Parnetti L, Squassina A, Tremolizzo L, Borroni B, Nacmias B, Sorbi S, Caffarra P, Seripa D, Rainero I, Daniele A, Masullo C, Spalletta G, Williams J, Amouyel P, Jessen F, Kehoe P, Tsolaki M, Rossi G, Sánchez-Juan P, Sleegers K, Ingelsson M, Andreassen OA, Hiltunen M, Van Duijn C, Sims R, van der Flier W, Ruiz A, Ramirez A, Lambert JC, and Frikke-Schmidt R
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- Humans, Female, Aged, Aged, 80 and over, Male, Cholesterol, HDL, Risk Factors, Causality, Alzheimer Disease epidemiology, Alzheimer Disease genetics
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Importance: An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most of these risk factors is lacking. Effective interventions should target risk factors in the causal pathway to dementia., Objective: To comprehensively disentangle potentially causal aspects of modifiable risk factors for Alzheimer disease (AD) to inspire new drug targeting and improved prevention., Design, Setting, and Participants: This genetic association study was conducted using 2-sample univariable and multivariable mendelian randomization. Independent genetic variants associated with modifiable risk factors were selected as instrumental variables from genomic consortia. Outcome data for AD were obtained from the European Alzheimer & Dementia Biobank (EADB), generated on August 31, 2021. Main analyses were conducted using the EADB clinically diagnosed end point data. All analyses were performed between April 12 and October 27, 2022., Exposures: Genetically determined modifiable risk factors., Main Outcomes and Measures: Odds ratios (ORs) and 95% CIs for AD were calculated per 1-unit change of genetically determined risk factors., Results: The EADB-diagnosed cohort included 39 106 participants with clinically diagnosed AD and 401 577 control participants without AD. The mean age ranged from 72 to 83 years for participants with AD and 51 to 80 years for control participants. Among participants with AD, 54% to 75% were female, and among control participants, 48% to 60% were female. Genetically determined high-density lipoprotein (HDL) cholesterol concentrations were associated with increased odds of AD (OR per 1-SD increase, 1.10 [95% CI, 1.05-1.16]). Genetically determined high systolic blood pressure was associated with increased risk of AD after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.22 [95% CI, 1.02-1.46]). In a second analysis to minimize bias due to sample overlap, the entire UK Biobank was excluded from the EADB consortium; odds for AD were similar for HDL cholesterol (OR per 1-SD unit increase, 1.08 [95% CI, 1.02-1.15]) and systolic blood pressure after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.23 [95% CI, 1.01-1.50])., Conclusions and Relevance: This genetic association study found novel genetic associations between high HDL cholesterol concentrations and high systolic blood pressure with higher risk of AD. These findings may inspire new drug targeting and improved prevention implementation.
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- 2023
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35. Clinimetrics of the cognitive section of the Italian ALS Cognitive Behavioral Screen (ALS-CBS™).
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Aiello EN, Greco LC, La Tona A, Solca F, Torre S, Carelli L, Pain D, Radici A, Lizio A, Casiraghi J, Cerri F, Brugnera A, Compare A, Woolley S, Murphy J, Tremolizzo L, Appollonio I, Verde F, Silani V, Ticozzi N, Lunetta C, Sansone VA, and Poletti B
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- Humans, Reproducibility of Results, Neuropsychological Tests, Italy, Cognition physiology, Cognition Disorders diagnosis, Cognition Disorders etiology, Amyotrophic Lateral Sclerosis complications, Amyotrophic Lateral Sclerosis diagnosis, Amyotrophic Lateral Sclerosis psychology, Cognitive Dysfunction diagnosis
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Background: The present study aimed at (1) providing further validity and reliability evidence for the Italian version of the cognitive section of the ALS Cognitive Behavioral Screen (ALS-CBS™) and (2) testing its diagnostics within an Italian ALS cohort, as well as at (3) exploring its capability to discriminate patients from healthy controls (HCs)., Methods: N = 293 non-demented ALS patients were administered the cognitive sections of the ALS-CBS™ and Edinburgh Cognitive and Behavioural ALS Screen (ECAS). N = 96 HCs demographically matched with N = 96 patients were also administered the cognitive section of the ALS-CBS™. In patients, factorial and construct validity, internal reliability, and diagnostics against a defective score on the cognitive section of the ECAS were tested. Case-control discrimination was assessed via a logistic regression., Results: ALS-CBS™ cognitive subscales were underpinned by a simple, unidimensional structure, internally reliable (McDonald's ω = 0.74), and mostly related with ECAS executive and fluency scores (r
s = 0.54-0.71). Both raw and age- and education-adjusted scores on the cognitive section of the ALS-CBS™ accurately detected ECAS-defined cognitive impairment (AUC = 0.80 and .88, respectively), yielding optimal error-based, information-based and unitary diagnostics. A cut-off of < 15.374 was identified on adjusted scores. The test was able to discriminate patients from HCs (p < 0.001)., Discussion: The cognitive section of the Italian ALS-CBS™ is a valid, reliable, and diagnostically sound ALS-specific screener for detecting frontotemporal, executive-/attentive-based cognitive inefficiency in non-demented ALS patients, being also able to discriminate them from normotypical individuals., (© 2022. Fondazione Società Italiana di Neurologia.)- Published
- 2023
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36. The HFE p.H63D (p.His63Asp) Polymorphism Is a Modifier of ALS Outcome in Italian and French Patients with SOD1 Mutations.
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Canosa A, Calvo A, Mora G, Moglia C, Brunetti M, Barberis M, Borghero G, Caponnetto C, Trojsi F, Spataro R, Volanti P, Simone IL, Salvi F, Logullo FO, Riva N, Tremolizzo L, Giannini F, Mandrioli J, Tanel R, Murru MR, Mandich P, Conforti FL, Zollino M, Sabatelli M, Tarlarini C, Lunetta C, Mazzini L, D'Alfonso S, Guy N, Meininger V, Clavelou P, Camu W, Chiò A, and On Behalf Of Italsgen Consortium
- Abstract
Background : Data from published studies about the effect of HFE polymorphisms on ALS risk, phenotype, and survival are still inconclusive. We aimed at evaluating whether the p.H63D polymorphism is a modifier of phenotype and survival in SOD1 -mutated patients. Methods : We included 183 SOD1 -mutated ALS patients. Mutations were classified as severe or mild according to the median survival of the study population. Patients were screened for the HFE p.H63D polymorphism. Survival was calculated using the Kaplan-Meier modeling, and differences were measured by the log-rank test. Multivariable analysis was performed with the Cox proportional hazards model (stepwise backward). Results : SOD1 severe mutation carriers show more frequent familial history for ALS and shorter survival compared to mild mutation carriers. Carriers and non-carriers of the p.H63D polymorphism did not differ in terms of sex ratio, frequency of positive familial history, age at onset, and bulbar/spinal ratio. In univariate and in Cox multivariable analysis using sex, age at onset, site of onset, family history, country of origin, and mutation severity as covariates, p.H63D carriers had a longer survival ( p = 0.034 and p = 0.004). Conclusions : We found that SOD1 -mutated ALS patients carrying the p.H63D HFE polymorphism have a longer survival compared to non-carriers, independently of sex, age and site of onset, family history, nation of origin, and severity of mutations, suggesting a possible role as disease progression modifier for the p.H63D HFE polymorphism in SOD1 -ALS., Competing Interests: Antonio Canosa serves on the Editorial Board of Biomedicines and serves as Guest Editor for the Special Issues ‘Recent Advances in Amyotrophic Lateral Sclerosis Genetics and Pathophysiology’ and ‘Recent Advances in Amyotrophic Lateral Sclerosis Genetics and Pathophysiology 2.0′ of Biomedicines. Andrea Calvo received a research grant from Cytokinetics. Adriano Chiò serves on scientific advisory boards for Mitsubishi Tanabe, Roche, Biogen, Cytokinetics, Denali, and AveXis, and received a research grant from Italfarmaco. Jessica Mandrioli received research support from Pfizer. The other authors have no conflict of interest relevant for the manuscript.
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- 2023
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37. Author Correction: Common variants in Alzheimer's disease and risk stratification by polygenic risk scores.
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de Rojas I, Moreno-Grau S, Tesi N, Grenier-Boley B, Andrade V, Jansen IE, Pedersen NL, Stringa N, Zettergren A, Hernández I, Montrreal L, Antúnez C, Antonell A, Tankard RM, Bis JC, Sims R, Bellenguez C, Quintela I, González-Perez A, Calero M, Franco-Macías E, Macías J, Blesa R, Cervera-Carles L, Menéndez-González M, Frank-García A, Royo JL, Moreno F, Huerto Vilas R, Baquero M, Diez-Fairen M, Lage C, García-Madrona S, García-González P, Alarcón-Martín E, Valero S, Sotolongo-Grau O, Ullgren A, Naj AC, Lemstra AW, Benaque A, Pérez-Cordón A, Benussi A, Rábano A, Padovani A, Squassina A, de Mendonça A, Arias Pastor A, Kok AAL, Meggy A, Pastor AB, Espinosa A, Corma-Gómez A, Martín Montes A, Sanabria Á, DeStefano AL, Schneider A, Haapasalo A, Kinhult Ståhlbom A, Tybjærg-Hansen A, Hartmann AM, Spottke A, Corbatón-Anchuelo A, Rongve A, Borroni B, Arosio B, Nacmias B, Nordestgaard BG, Kunkle BW, Charbonnier C, Abdelnour C, Masullo C, Martínez Rodríguez C, Muñoz-Fernandez C, Dufouil C, Graff C, Ferreira CB, Chillotti C, Reynolds CA, Fenoglio C, Van Broeckhoven C, Clark C, Pisanu C, Satizabal CL, Holmes C, Buiza-Rueda D, Aarsland D, Rujescu D, Alcolea D, Galimberti D, Wallon D, Seripa D, Grünblatt E, Dardiotis E, Düzel E, Scarpini E, Conti E, Rubino E, Gelpi E, Rodriguez-Rodriguez E, Duron E, Boerwinkle E, Ferri E, Tagliavini F, Küçükali F, Pasquier F, Sanchez-Garcia F, Mangialasche F, Jessen F, Nicolas G, Selbæk G, Ortega G, Chêne G, Hadjigeorgiou G, Rossi G, Spalletta G, Giaccone G, Grande G, Binetti G, Papenberg G, Hampel H, Bailly H, Zetterberg H, Soininen H, Karlsson IK, Alvarez I, Appollonio I, Giegling I, Skoog I, Saltvedt I, Rainero I, Rosas Allende I, Hort J, Diehl-Schmid J, Van Dongen J, Vidal JS, Lehtisalo J, Wiltfang J, Thomassen JQ, Kornhuber J, Haines JL, Vogelgsang J, Pineda JA, Fortea J, Popp J, Deckert J, Buerger K, Morgan K, Fließbach K, Sleegers K, Molina-Porcel L, Kilander L, Weinhold L, Farrer LA, Wang LS, Kleineidam L, Farotti L, Parnetti L, Tremolizzo L, Hausner L, Benussi L, Froelich L, Ikram MA, Deniz-Naranjo MC, Tsolaki M, Rosende-Roca M, Löwenmark M, Hulsman M, Spallazzi M, Pericak-Vance MA, Esiri M, Bernal Sánchez-Arjona M, Dalmasso MC, Martínez-Larrad MT, Arcaro M, Nöthen MM, Fernández-Fuertes M, Dichgans M, Ingelsson M, Herrmann MJ, Scherer M, Vyhnalek M, Kosmidis MH, Yannakoulia M, Schmid M, Ewers M, Heneka MT, Wagner M, Scamosci M, Kivipelto M, Hiltunen M, Zulaica M, Alegret M, Fornage M, Roberto N, van Schoor NM, Seidu NM, Banaj N, Armstrong NJ, Scarmeas N, Scherbaum N, Goldhardt O, Hanon O, Peters O, Skrobot OA, Quenez O, Lerch O, Bossù P, Caffarra P, Dionigi Rossi P, Sakka P, Mecocci P, Hoffmann P, Holmans PA, Fischer P, Riederer P, Yang Q, Marshall R, Kalaria RN, Mayeux R, Vandenberghe R, Cecchetti R, Ghidoni R, Frikke-Schmidt R, Sorbi S, Hägg S, Engelborghs S, Helisalmi S, Botne Sando S, Kern S, Archetti S, Boschi S, Fostinelli S, Gil S, Mendoza S, Mead S, Ciccone S, Djurovic S, Heilmann-Heimbach S, Riedel-Heller S, Kuulasmaa T, Del Ser T, Lebouvier T, Polak T, Ngandu T, Grimmer T, Bessi V, Escott-Price V, Giedraitis V, Deramecourt V, Maier W, Jian X, Pijnenburg YAL, Kehoe PG, Garcia-Ribas G, Sánchez-Juan P, Pastor P, Pérez-Tur J, Piñol-Ripoll G, Lopez de Munain A, García-Alberca JM, Bullido MJ, Álvarez V, Lleó A, Real LM, Mir P, Medina M, Scheltens P, Holstege H, Marquié M, Sáez ME, Carracedo Á, Amouyel P, Schellenberg GD, Williams J, Seshadri S, van Duijn CM, Mather KA, Sánchez-Valle R, Serrano-Ríos M, Orellana A, Tárraga L, Blennow K, Huisman M, Andreassen OA, Posthuma D, Clarimón J, Boada M, van der Flier WM, Ramirez A, Lambert JC, van der Lee SJ, and Ruiz A
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- 2023
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38. Standardization of the Italian ALS-CBS™ Caregiver Behavioral Questionnaire.
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Aiello EN, Solca F, Greco LC, La Tona A, Torre S, Carelli L, Morelli C, Doretti A, Colombo E, Messina S, Pain D, Radici A, Lizio A, Casiraghi J, Cerri F, Brugnera A, Compare A, Woolley S, Murphy J, Tremolizzo L, Appollonio I, Verde F, Sansone VA, Lunetta C, Silani V, Ticozzi N, and Poletti B
- Abstract
Background: The present investigation aimed at testing the psychometrics and diagnostics of the Italian version of the Caregiver Behavioral Questionnaire (CBQ) from the ALS Cognitive Behavioral Screen (ALS-CBS™), as well as its case-control discrimination, in a cohort of non-demented patients with ALS., Methods: The caregivers of N = 265 non-demented patients with ALS and N = 99 healthy controls (HCs) were administered the CBQ and the Edinburgh Cognitive and Behavioural ALS Screen-Carer Interview (ECAS-CI). For N = 98 patients, an in-depth behavioural/psychopathological assessment via the Frontal Behavioural Inventory (FBI), the Dimensional Apathy Scale (DAS), the State and Trait Anxiety Inventory-Form Y (STAI-Y), and the Beck Depression Inventory (BDI) was also available. Factorial and construct validity, internal reliability, and diagnostics against an abnormal ECAS-CI score were tested in patients. Case-control discrimination was explored through logistic regression., Results: The CBQ was internally reliable (McDonald's ω = 0.90) and underpinned by a simple, unidimensional structure; it converged with ECAS-CI, FBI, and DAS scores and diverged from STAI-Y and BDI ones. A cutoff of ≤ 33 accurately detected abnormal ECAS-CI scores (AUC = 0.85), yielding optimal error- and information-based diagnostics. The CBQ was independent of demographic and disease-related variables and discriminated patients from HCs ( p < 0.001)., Discussion: The Italian version of the CBQ from the ALS-CBS™ is a valid, reliable, diagnostically sound, and feasible screener for detecting frontotemporal-like behavioural changes in non-demented patients with ALS. Its adoption is thus recommended within clinical practice and research in the view of providing preliminary information on whether the administration of more extensive behavioural instruments is needed., Competing Interests: VS received compensation for consulting services and/or speaking activities from AveXis, Cytokinetics, Italfarmaco, Liquidweb S.r.l., and Novartis Pharma AG and receives or has received research supports from the Italian Ministry of Health, AriSLA, and E-Rare Joint Transnational Call. He is in the Editorial Board of Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, European Neurology and the American Journal of Neurodegenerative Diseases. BP and LC received compensation for consulting services and/or speaking activities from Liquidweb S.r.l. NT received compensation for consulting services from Amylyx Pharmaceuticals and Zambon Biotech SA. CL received compensation for consulting services and/or speaking activities from Cytokinetics, Italfarmaco, and Mitsubishi Tanabe Pharma Europe. VAS participates in Advisory Boards or teaching activities for Biogen, Roche, Avexis, PTC, Santhera, Sarepta, and Dyne. SW is employed by Syneos Health. Additionally, SW receives licensing fees when the ALS Cognitive Behavioural Screen (ALS-CBS™) is used in pharmaceutical trials. JM is employed full time at Biogen. JM does not receive compensation related to the ALS-CBS™. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Aiello, Solca, Greco, La Tona, Torre, Carelli, Morelli, Doretti, Colombo, Messina, Pain, Radici, Lizio, Casiraghi, Cerri, Brugnera, Compare, Woolley, Murphy, Tremolizzo, Appollonio, Verde, Sansone, Lunetta, Silani, Ticozzi and Poletti.)
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- 2023
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39. Can Traditional Board Games Prevent or Slow Down Cognitive Impairment? A Systematic Review and Meta-Analysis.
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Pozzi FE, Appollonio I, Ferrarese C, and Tremolizzo L
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- Humans, Aged, Quality of Life, Cognition, Executive Function, Cognitive Dysfunction prevention & control, Cognitive Dysfunction psychology, Alzheimer Disease
- Abstract
Background: Traditional board games can entail significant skills encompassing several cognitive functions across different domains. Therefore, they may potentially represent effective cognitive interventions in the aging population with or without Alzheimer's disease or other types of dementia., Objective: We aimed at verifying the hypothesis that traditional board games can prevent or slow down cognitive decline, through a systematic review on traditional board games and dementia., Methods: We searched five databases with tailored search strings. We included studies assessing the impact of board games on elderly subjects at risk of or suffering from cognitive impairment, or subjects with cognitive impairment irrespective of age. Studies where the effect of board games was not separated by cards or other games were excluded. A meta-analysis was performed for specific cognitive and non-cognitive outcomes., Results: Board games improved mental function, as measured by Montreal Cognitive Assessment (p = 0.003) and Mini-Mental State Examination (p = 0.02). Ska and Go improved Trail Making Test -A, while Mahjong improved executive functions. There was no consistent effect across different games on Digit Span or Categorical Fluency. Chess improved quality of life measured with the WHO-QoL-OLD scale (p < 0.00001). Mahjong temporarily improved depressive symptoms. Go increased BDNF levels and left middle temporal gyrus and bilateral putamen metabolism., Conclusions: Traditional board games may slow global cognitive decline and improve the quality of life in elderly subjects. Different games have varying impacts on specific cognitive domains, possibly mediated by functional and biological factors.
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- 2023
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40. Correction to: ALS Cognitive Behavioral Screen‑Phone Version (ALS‑CBS™‑PhV): norms, psychometrics, and diagnostics in an Italian population sample.
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Aiello EN, Esposito A, Giannone I, Diana L, Woolley S, Murphy J, Christodoulou G, Tremolizzo L, Bolognini N, and Appollonio I
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- 2023
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41. TSPO Modulates Oligomeric Amyloid-β-Induced Monocyte Chemotaxis: Relevance for Neuroinflammation in Alzheimer's Disease.
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Conti E, Grana D, Angiulli F, Karantzoulis A, Villa C, Combi R, Appollonio I, Ferrarese C, and Tremolizzo L
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- Humans, Monocytes metabolism, Chemotaxis, Neuroinflammatory Diseases, Amyloid beta-Peptides pharmacology, Amyloid beta-Peptides metabolism, Receptors, GABA metabolism, Alzheimer Disease
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Background: Neuroinflammation is one of the cardinal mechanisms of Alzheimer's disease (AD). with amyloid-β (Aβ) playing a critical role by activating microglia to produce soluble inflammatory mediators, including several chemokines. Peripheral monocytes are, therefore, attracted into the central nervous system (CNS), where they change into blood-born microglia and participate in the attempt of removing toxic Aβ species. The translocator protein-18 kDa (TSPO) is a transmembrane protein overexpressed in response to neuroinflammation and known to regulate human monocyte chemotaxis., Objective: We aimed to evaluate the role of the oligomeric Aβ1-42 isoform at inducing peripheral monocyte chemotaxis, and the possible involvement of TSPO in this process., Methods: In vitro cell lines, and ex vivo monocytes from consecutive AD patients (n = 60), and comparable cognitively intact controls (n = 30) were used. Chemotaxis analyses were carried out through both μ-slide chambers and Boyden assays, using 125 pM oligomeric Aβ1-42 as chemoattractant. TSPO agonists and antagonists were tested (Ro5-4864, Emapunil, PK11195)., Results: Oligomeric Aβ directly promoted chemotaxis in all our models. Interestingly, AD monocytes displayed a stronger response (about twofold) with respect to controls. Aβ-induced chemotaxis was prevented by the TSPO antagonist PK11195; the expression of the TSPO and of the C-C chemokine receptor type 2 (CCR2) was unchanged by drug exposure., Conclusion: Oligomeric Aβ1-42 is able to recruit peripheral monocytes, and we provide initial evidence sustaining a role for TSPO in modulating this process. This data may be of value for future therapeutic interventions aimed at modulating monocytes motility toward the CNS.
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- 2023
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42. Resting state functional brain networks associated with emotion processing in frontotemporal lobar degeneration.
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Canu E, Calderaro D, Castelnovo V, Basaia S, Magno MA, Riva N, Magnani G, Caso F, Caroppo P, Prioni S, Villa C, Pain D, Mora G, Tremolizzo L, Appollonio I, Poletti B, Silani V, Filippi M, and Agosta F
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- Humans, Brain, Brain Mapping, Magnetic Resonance Imaging, Frontotemporal Dementia, Frontotemporal Lobar Degeneration pathology
- Abstract
This study investigated the relationship between emotion processing and resting-state functional connectivity (rs-FC) of the brain networks in frontotemporal lobar degeneration (FTLD). Eighty FTLD patients (including cases with behavioral variant of frontotemporal dementia, primary progressive aphasia, progressive supranuclear palsy syndrome, motor neuron disease) and 65 healthy controls underwent rs-functional MRI. Emotion processing was tested using the Comprehensive Affect Testing System (CATS). In patients and controls, correlations were investigated between each emotion construct and rs-FC changes within critical networks. Mean rs-FC of the clusters significantly associated with CATS scoring were compared among FTLD groups. FTLD patients had pathological CATS scores compared with controls. In controls, increased rs-FC of the cerebellar and visuo-associative networks correlated with better scores in emotion-matching and discrimination tasks, respectively; while decreased rs-FC of the visuo-spatial network was related with better performance in the affect-matching and naming. In FTLD, the associations between rs-FC and CATS scores involved more brain regions, such as orbitofrontal and middle frontal gyri within anterior networks (i.e., salience and default-mode), parietal and somatosensory regions within visuo-spatial and sensorimotor networks, caudate and thalamus within basal-ganglia network. Rs-FC changes associated with CATS were similar among all FTLD groups. In FTLD compared to controls, the pattern of rs-FC associated with emotional processing involves a larger number of brain regions, likely due to functional specificity loss and compensatory attempts. These associations were similar across all FTLD groups, suggesting a common physiopathological mechanism of emotion processing breakdown, regardless the clinical presentation and pattern of atrophy., (© 2022. The Author(s).)
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- 2022
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43. Tics: neurological disorders determined by a deficit in sensorimotor gating processes.
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Schilke ED, Tremolizzo L, Appollonio I, and Ferrarese C
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- Humans, Prepulse Inhibition, Reflex, Startle physiology, Sensory Gating physiology, Tics, Tourette Syndrome
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Tic related disorders affect 4-20% of the population, mostly idiopathic, can be grouped in a wide spectrum of severity, where the most severe end is Tourette Syndrome (TS). Tics are arrhythmic hyperkinesias to whom execution the subject is forced by a "premonitory urge" that can be classified as sensory tic, just-right experience or urge without obsession. If an intact volitional inhibition allows patients to temporarily suppress tics, a lack or deficit in automatic inhibition is involved in the genesis of the disorder. Studies have assessed the presence of intrinsic microscopic and macroscopic anomalies in striatal circuits and relative cortical areas in association with a hyperdopaminergic state in the basal forebrain. Prepulse inhibition (PPI) of the startle reflex is a measure of inhibitory functions by which a weak sensory stimulus inhibits the elicitation of a startle response determined by a sudden intense stimulus. It is considered an operation measure of sensorimotor gating, a neural process by which unnecessary stimuli are eliminated from awareness. Evidence points out that the limbic domain of the CSTC loops, dopamine and GABA receptors within the striatum play an important role in PPI modulation. It is conceivable that a sensorimotor gating deficit may be involved in the genesis of premonitory urge and symptoms. Therefore, correcting the sensorimotor gating deficit may be considered a target for tic-related disorders therapies; in such case PPI (as well as other indirect estimators of sensorimotor gating) could represent therapeutic impact predictors., (© 2022. The Author(s).)
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- 2022
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44. Neurological soft signs are increased in migraine without aura: relationship with the affective status.
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Tremolizzo L, Selvatico D, Pozzi FE, Cereda D, DiFrancesco JC, Fumagalli L, Ferrarese C, and Appollonio I
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- Headache, Humans, Magnetic Resonance Imaging, Neurologic Examination, Quality of Life, Migraine without Aura, Schizophrenia pathology
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Introduction: Neurological soft signs (NSS) are subtle non-localizing sensorimotor abnormalities initially reported as increased in primary headache patients. The aims of this study were confirming with full power NSS increased expression in migraine and, collaterally, determining if psychiatric traits or white matter lesions at brain imaging could influence this result., Methods: Forty drug-free episodic migraine outpatients (MH) were recruited with 40 matched controls. NSS were determined by the 16-item Heidelberg scale; depression, anxiety and QoL by the HAM-D; the STAI-X1/X2; and the SF36, respectively. The Fazekas scale on brain MR studies was applied in n = 32 MH, unravelling deep white matter signal alterations (DWM). MH characteristics, including the headache disability inventory (HDI), were recorded., Results: NSS were 46% increased in MH vs. controls (p = 0.0001). HAM-D and STAI-X1/X2 were increased in MH, while SF36 was unchanged, but they all failed to influence NSS, just as MH characteristics. NSS scores were increased in MH-DWM + (n = 11, + 85%) vs. MH-DWM - (n = 21, + 27%) vs. controls (p < 0.0001). NSS increased expression in MH was influenced by DWM, while psychiatric traits and headache characteristics failed to do so., Discussion/conclusions: NSS are increased in MH and probably not influenced by the affective status, possibly marking a dysfunction within the cerebellar-thalamic-prefrontal circuit that may deserve further attention from the prognostic point of view., (© 2022. The Author(s).)
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- 2022
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45. Predictors of response to acetylcholinesterase inhibitors in dementia: A systematic review.
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Pozzi FE, Conti E, Appollonio I, Ferrarese C, and Tremolizzo L
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Background: The mainstay of therapy for many neurodegenerative dementias still relies on acetylcholinesterase inhibitors (AChEI); however, there is debate on various aspects of such treatment. A huge body of literature exists on possible predictors of response, but a comprehensive review is lacking. Therefore, our aim is to perform a systematic review of the predictors of response to AChEI in neurodegenerative dementias, providing a categorization and interpretation of the results., Methods: We conducted a systematic review of the literature up to December 31
st , 2021, searching five different databases and registers, including studies on rivastigmine, donepezil, and galantamine, with clearly defined criteria for the diagnosis of dementia and the response to AChEI therapy. Records were identified through the string: predict* AND respon* AND (acetylcholinesterase inhibitors OR donepezil OR rivastigmine OR galantamine) . The results were presented narratively., Results: We identified 1,994 records in five different databases; after exclusion of duplicates, title and abstract screening, and full-text retrieval, 122 studies were finally included., Discussion: The studies show high heterogeneity in duration, response definition, drug dosage, and diagnostic criteria. Response to AChEI seems associated with correlates of cholinergic deficit (hallucinations, fluctuating cognition, substantia innominate atrophy) and preserved cholinergic neurons (faster alpha on REM sleep EEG, increased anterior frontal and parietal lobe perfusion after donepezil); white matter hyperintensities in the cholinergic pathways have shown inconsistent results. The K-variant of butyrylcholinesterase may correlate with better response in late stages of disease, while the role of polymorphisms in other genes involved in the cholinergic system is controversial. Factors related to drug availability may influence response; in particular, low serum albumin (for donepezil), CYP2D6 variants associated with reduced enzymatic activity and higher drug doses are the most consistent predictors, while AChEI concentration influence on clinical outcomes is debatable. Other predictors of response include faster disease progression, lower serum cholesterol, preserved medial temporal lobes, apathy, absence of concomitant diseases, and absence of antipsychotics. Short-term response may predict subsequent cognitive response, while higher education might correlate with short-term good response (months), and long-term poor response (years). Age, gender, baseline cognitive and functional levels, and APOE relationship with treatment outcome is controversial., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pozzi, Conti, Appollonio, Ferrarese and Tremolizzo.)- Published
- 2022
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46. Donepezil-Induced Complex Multimodal Hallucinations: Two Cases and a Review of the Literature.
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Pozzi FE, Tremolizzo L, Ferrarese C, and Appollonio I
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Hallucinations are common in neurodegenerative dementias, being present in a significant proportion of patients. Most of the available studies show that acetylcholinesterase inhibitors may be beneficial in preventing and treating hallucinations in patients with neurodegenerative and even psychiatric disorders, even though there are reports that they might also develop as an adverse effect of such therapy. However, a clear causal relationship for the latter association was not previously established. Here we describe 2 cases of patients treated with donepezil who developed complex multimodal hallucinations, which could be causally linked to the drug by means of a challenge-dechallenge (and rechallenge in one case) paradigm. We also provide a narrative review of the literature regarding donepezil and hallucinations and propose a hypothesis to explain the occurrence of this phenomenon., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel.)
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- 2022
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47. Association of Rare APOE Missense Variants V236E and R251G With Risk of Alzheimer Disease.
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Le Guen Y, Belloy ME, Grenier-Boley B, de Rojas I, Castillo-Morales A, Jansen I, Nicolas A, Bellenguez C, Dalmasso C, Küçükali F, Eger SJ, Rasmussen KL, Thomassen JQ, Deleuze JF, He Z, Napolioni V, Amouyel P, Jessen F, Kehoe PG, van Duijn C, Tsolaki M, Sánchez-Juan P, Sleegers K, Ingelsson M, Rossi G, Hiltunen M, Sims R, van der Flier WM, Ramirez A, Andreassen OA, Frikke-Schmidt R, Williams J, Ruiz A, Lambert JC, Greicius MD, Arosio B, Benussi L, Boland A, Borroni B, Caffarra P, Daian D, Daniele A, Debette S, Dufouil C, Düzel E, Galimberti D, Giedraitis V, Grimmer T, Graff C, Grünblatt E, Hanon O, Hausner L, Heilmann-Heimbach S, Holstege H, Hort J, Jürgen D, Kuulasmaa T, van der Lugt A, Masullo C, Mecocci P, Mehrabian S, de Mendonça A, Moebus S, Nacmias B, Nicolas G, Olaso R, Papenberg G, Parnetti L, Pasquier F, Peters O, Pijnenburg YAL, Popp J, Rainero I, Ramakers I, Riedel-Heller S, Scarmeas N, Scheltens P, Scherbaum N, Schneider A, Seripa D, Soininen H, Solfrizzi V, Spalletta G, Squassina A, van Swieten J, Tegos TJ, Tremolizzo L, Verhey F, Vyhnalek M, Wiltfang J, Boada M, García-González P, Puerta R, Real LM, Álvarez V, Bullido MJ, Clarimon J, García-Alberca JM, Mir P, Moreno F, Pastor P, Piñol-Ripoll G, Molina-Porcel L, Pérez-Tur J, Rodríguez-Rodríguez E, Royo JL, Sánchez-Valle R, Dichgans M, and Rujescu D
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- Age of Onset, Alleles, Apolipoprotein E2 genetics, Apolipoprotein E4 genetics, Apolipoproteins E genetics, Female, Genotype, Humans, Male, Alzheimer Disease epidemiology, Alzheimer Disease genetics
- Abstract
Importance: The APOE ε2 and APOE ε4 alleles are the strongest protective and risk-increasing, respectively, genetic variants for late-onset Alzheimer disease (AD). However, the mechanisms linking APOE to AD-particularly the apoE protein's role in AD pathogenesis and how this is affected by APOE variants-remain poorly understood. Identifying missense variants in addition to APOE ε2 and APOE ε4 could provide critical new insights, but given the low frequency of additional missense variants, AD genetic cohorts have previously been too small to interrogate this question robustly., Objective: To determine whether rare missense variants on APOE are associated with AD risk., Design, Setting, and Participants: Association with case-control status was tested in a sequenced discovery sample (stage 1) and followed up in several microarray imputed cohorts as well as the UK Biobank whole-exome sequencing resource using a proxy-AD phenotype (stages 2 and 3). This study combined case-control, family-based, population-based, and longitudinal AD-related cohorts that recruited referred and volunteer participants. Stage 1 included 37 409 nonunique participants of European or admixed European ancestry, with 11 868 individuals with AD and 11 934 controls passing analysis inclusion criteria. In stages 2 and 3, 475 473 participants were considered across 8 cohorts, of which 84 513 individuals with AD and proxy-AD and 328 372 controls passed inclusion criteria. Selection criteria were cohort specific, and this study was performed a posteriori on individuals who were genotyped. Among the available genotypes, 76 195 were excluded. All data were retrieved between September 2015 and November 2021 and analyzed between April and November 2021., Main Outcomes and Measures: In primary analyses, the AD risk associated with each missense variant was estimated, as appropriate, with either linear mixed-model regression or logistic regression. In secondary analyses, associations were estimated with age at onset using linear mixed-model regression and risk of conversion to AD using competing-risk regression., Results: A total of 544 384 participants were analyzed in the primary case-control analysis; 312 476 (57.4%) were female, and the mean (SD; range) age was 64.9 (15.2; 40-110) years. Two missense variants were associated with a 2-fold to 3-fold decreased AD risk: APOE ε4 (R251G) (odds ratio, 0.44; 95% CI, 0.33-0.59; P = 4.7 × 10-8) and APOE ε3 (V236E) (odds ratio, 0.37; 95% CI, 0.25-0.56; P = 1.9 × 10-6). Additionally, the cumulative incidence of AD in carriers of these variants was found to grow more slowly with age compared with noncarriers., Conclusions and Relevance: In this genetic association study, a novel variant associated with AD was identified: R251G always coinherited with ε4 on the APOE gene, which mitigates the ε4-associated AD risk. The protective effect of the V236E variant, which is always coinherited with ε3 on the APOE gene, was also confirmed. The location of these variants confirms that the carboxyl-terminal portion of apoE plays an important role in AD pathogenesis. The large risk reductions reported here suggest that protein chemistry and functional assays of these variants should be pursued, as they have the potential to guide drug development targeting APOE.
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- 2022
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48. Validation of the DYALS (dysphagia in amyotrophic lateral sclerosis) questionnaire for the evaluation of dysphagia in ALS patients.
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Diamanti L, Borrelli P, Dubbioso R, Capasso M, Morelli C, Lunetta C, Petrucci A, Mora G, Volanti P, Inghilleri M, Tremolizzo L, Mandrioli J, Mazzini L, Vedovello M, Siciliano G, Filosto M, Matà S, and Montomoli C
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- Humans, Middle Aged, Quality of Life, Surveys and Questionnaires, Amyotrophic Lateral Sclerosis complications, Amyotrophic Lateral Sclerosis diagnosis, Deglutition Disorders diagnosis, Deglutition Disorders etiology, Multiple Sclerosis diagnosis
- Abstract
Background: Dysphagia is a common symptom during the trajectory of ALS, and it can significantly impact on the quality of life and prognosis of patients. Nowadays, no specific tool for the screening of dysphagia in ALS is validated, and the approach is heterogeneous across the Italian centres., Objective: To validate the DYALS (dysphagia in amyotrophic lateral sclerosis) questionnaire, adapting the DYMUS (dysphagia in multiple sclerosis) questionnaire, for the assessment of dysphagia in ALS patients, in order to uniform the evaluations across the Italian ALS network., Methods: We included 197 patients diagnosed with ALS following the El Escorial criteria, in sixteen Italian ALS centres between 1st December 2019 and 1st July 2020. For each patient, we collected clinical and demographic data and obtained ALSFRS-r score, ALSAQ-5 score, DYMUS score, and EAT-10 score., Results: Across the 197 patients, the ratio M/F was 113/84, and the median age was 64 years (IQR 56-72.5). Bulbar patients were 20%, and spinal patients 80%. The median ALSFRSr total score of patients was 35 (IQR 28-39). DYALS score was statistically higher in bulbar ALS than in spinal ALS (median = 6, IQR 4.5-9 vs median = 1, IQR 0-5, z = 6.253, p < 0.0001). DYALS questionnaire showed a high internal consistency (Cronbach's alpha = 0.88). There was a statistically significant correlation between DYALS and EAT-10 (rho = 0.90, p < 0.0001)., Conclusions: DYALS scale is reliable, manageable, and easily usable for the screening of dysphagia in ALS. It can be shared with all the Italian ALS centres in order to collect uniform data for therapeutic strategies and clinical trials., (© 2021. Fondazione Società Italiana di Neurologia.)
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- 2022
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49. A preliminary comparison between ECAS and ALS-CBS in classifying cognitive-behavioural phenotypes in a cohort of non-demented amyotrophic lateral sclerosis patients.
- Author
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Greco LC, Lizio A, Casiraghi J, Sansone VA, Tremolizzo L, Riva N, Solca F, Torre S, Ticozzi N, Filippi M, Silani V, Poletti B, and Lunetta C
- Subjects
- Adult, Cognition, Humans, Middle Aged, Neuropsychological Tests, Phenotype, Amyotrophic Lateral Sclerosis diagnosis, Amyotrophic Lateral Sclerosis psychology, Cognition Disorders diagnosis, Cognition Disorders etiology
- Abstract
To define the presence and type of frontotemporal dysfunction in amyotrophic lateral sclerosis (ALS), different screening tools have been created. Currently, the most used screening tests are the Edinburgh cognitive and behavioural ALS screen (ECAS) and the ALS cognitive behavioural screen (ALS-CBS). The objective of this study was to compare the ability of ECAS and ALS-CBS in classifying non-demented ALS patients according to Strong criteria. One-hundred and fifty-four in- and out-patients with an age > 18 and a definite or probable ALS diagnosis were recruited between September 2019 and February 2020 at NeMO Clinical Centre and at Istituto Auxologico Italiano in Milan and underwent the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) and the ALS Cognitive Behavioural Screen (ALS-CBS). Exclusion criteria involved patients with a diagnosis of FTD, with a severe cognitive deterioration and/or an important behavioural impairment, with a significant psychiatric disorder or with the co-presence of another significant illness. The distribution of patients according to Strong criteria was different for ECAS and ALS-CBS and the degree of agreement between the two tests in terms of Cohen's Kappa coefficient resulted equal to 0.2047 with a 95% confidence limits interval between 0.1122 and 0.2973. This study for the first time compares the ability of ECAS and ALS-CBS in stratifying ALS patients. Further studies will be conducted to better understand the reasons underlying the differences between these two tests in classifying the different subtypes of fronto-temporal dysfunction in ALS., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2022
- Full Text
- View/download PDF
50. Clinical Perception and Treatment Options for Behavioral and Psychological Symptoms of Dementia (BPSD) in Italy.
- Author
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D'Antonio F, Tremolizzo L, Zuffi M, Pomati S, and Farina E
- Abstract
Background: Behavioral and psychological symptoms of dementia (BPSD) have a high prevalence, and their presence is associated with a severe impact in terms of social costs. However, dedicated clinical tools or biomarkers to detect these symptoms are lacking. Thus, BPSD management in clinical settings is challenging. The aim of this study was to investigate the perception and the treatment strategies for BPSD in Italian centers working in the dementia field., Methods: A multicenter, national survey was developed by BPSD Study Group of the Italian Neurological Society for Dementia (SINDEM). The survey consisted of a semi-structured questionnaire that was e-mailed to SINDEM members, dementia centers part of the national network of memory clinics (Centers for Cognitive Deterioration and Dementia [CDCD]), and clinicians working in dementia care settings. The questions were focused on (1) perceived global frequency and relevance of BPSD; (2) tools used to assess BPSD; (3) pharmacological treatment for psychosis, apathy, agitation, aggression, depression, anxiety, sleep, and nutrition disturbances; (4) non-pharmacological treatments; (5) drugs side effects., Results: One-hundred and thirty-six clinicians participated in this study. Seventy-nine participants worked in a CDCD and 57 in other settings. The perceived frequency of BPSD was 74%. BPSD are detected by means of a clinical assessment for 96.3% or a caregiver interview for 97%. For psychosis treatment the first choice was atypical antipsychotics (83.3%), followed by typical antipsychotic (8.9%) and antidepressants (4.8%). For agitation, atypical antipsychotics were the first-choice treatment in 64% of cases and antidepressants in 16.1%. For aggression, the most used drugs were atypical antipsychotics (82.9%). For anxiety, 55.2% use antidepressants, 17.9% use atypical antipsychotics, and 16.9% use benzodiazepines. Interestingly, most of the centers apply non-pharmacological treatments for BPSD. Some differences emerged comparing the responses from CDCD and other care settings., Conclusion: The survey results revealed many differences in BPSD perception, treatment options, and observed side effect according to the clinical setting. This variability can be explained by the absence of clear guidelines, by differences in patients' characteristics, and by clinical practice based on subjective experience. These results suggest that producing guidelines for the pharmacological treatment of BPSD is a major need., Competing Interests: EF was employed by IRCCS Don Gnocchi Foundation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 D'Antonio, Tremolizzo, Zuffi, Pomati, Farina and the Sindem BPSD Study Group.)
- Published
- 2022
- Full Text
- View/download PDF
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