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1. Locus Coeruleus magnetic resonance imaging: a comparison between native-space and template-space approach

Author: Giorgi, F. S., Martini, N., Lombardo, F., Galgani, A., Bastiani, L., Della Latta, D., Hlavata, H., Busceti, C. L., Biagioni, F., Puglisi-Allegra, S., Pavese, N., and Fornai, F.
Published: 2022
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2. A short overview on the role of α-synuclein and proteasome in experimental models of Parkinson’s disease

Author: Giorgi, F. S., Bandettini di Poggio, A., Battaglia, G., Pellegrini, A., Murri, L., Ruggieri, S., Paparelli, A., Fornai, F., Riederer, P., editor, Reichmann, H., editor, Youdim, M. B. H., editor, and Gerlach, M., editor
Published: 2006
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3. Brivaracetam as Early Add-On Treatment in Patients with Focal Seizures: A Retrospective, Multicenter, RealWorld Study

Author: Lattanzi, S., Canafoglia, L., Canevini, M. P., Casciato, S., Cerulli Irelli, E., Chiesa, V., Dainese, F., De Maria, G., Didato, G., Di Gennaro, G., Falcicchio, G., Fanella, M., Ferlazzo, E., Gangitano, M., La Neve, A., Mecarelli, O., Montalenti, E., Morano, A., Piazza, F., Pizzanelli, C., Pulitano, P., Ranzato, F., Rosati, E., Tassi, L., Di Bonaventura, C., Alicino, A., Ascoli, M., Assenza, G., Avorio, F., Badioni, V., Banfi, P., Bartolini, E., Basili, L. M., Belcastro, V., Beretta, S., Berto, I., Biggi, M., Billo, G., Boero, G., Bonanni, P., Bongorno, J., Brigo, F., Caggia, E., Cagnetti, C., Calvello, C., Cesnik, E., Chianale, G., Ciampanelli, D., Ciuffini, R., Cocito, D., Colella, D., Contento, M., Costa, C., Cumbo, E., D'Aniello, A., Deleo, F., Difrancesco, J. C., Di Giacomo, R., Di Liberto, A., Domina, E., Dono, F., Durante, V., Elia, M., Estraneo, A., Evangelista, G., Faedda, M. T., Failli, Y., Fallica, E., Fattouch, J., Ferrari, A., Ferreri, F., Fisco, G., Fonti, D., Fortunato, F., Foschi, N., Francavilla, T., Galli, R., Gazzina, S., Giallonardo, A. T., Giorgi, F. S., Giuliano, L., Habetswallner, F., Izzi, F., Kassabian, B., Labate, A., Luisi, C., Magliani, M., Maira, G., Mari, L., Marino, D., Mascia, A., Mazzeo, A., Meletti, S., Milano, C., Nilo, A., Orlando, B., Paladin, F., Pascarella, M. G., Pastori, C., Pauletto, G., Peretti, A., Perri, G., Pezzella, M., Piccioli, M., Pignatta, P., Pilolli, N., Pisani, F., Pisani, L. R., Placidi, F., Pollicino, P., Porcella, V., Pradella, S., Puligheddu, M., Quadri, S., Quarato, P. P., Quintas, R., Renna, R., Rizzo, G. R., Rum, A., Salamone, E. M., Savastano, E., Sessa, M., Stokelj, D., Tartara, E., Tombini, M., Tumminelli, G., Vaudano, A. E., Ventura, M., Vigano, I., Viglietta, E., Vignoli, A., Villani, F., Zambrelli, E., Zummo, L., Lattanzi, Simona, Canafoglia, Laura, Canevini, Maria Paola, Casciato, Sara, Cerulli Irelli, Emanuele, Chiesa, Valentina, Dainese, Filippo, De Maria, Giovanni, Didato, Giuseppe, Di Gennaro, Giancarlo, Falcicchio, Giovanni, Fanella, Martina, Ferlazzo, Edoardo, Gangitano, Massimo, La Neve, Angela, Mecarelli, Oriano, Montalenti, Elisa, Morano, Alessandra, Piazza, Federico, Pizzanelli, Chiara, Pulitano, Patrizia, Ranzato, Federica, Rosati, Eleonora, Tassi, Laura, and Di Bonaventura, Carlo
Subjects: Antiseizure medication, Focal seizures, Brivaracetam, Epilepsy, Neurology, Settore MED/26 - Neurologia, Neurology (clinical), Settore MED/26, Settore MED/39 - Neuropsichiatria Infantile
Abstract: Introduction: In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Most real-world research on BRV has focused on refractory epilepsy. The aim of this analysis was to assess the 12-month effectiveness and tolerability of adjunctive BRV when used as early or late adjunctive treatment in patients included in the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST). Methods: BRIVAFIRST was a 12-month retrospective, multicenter study including adult patients prescribed adjunctive BRV. Effectiveness outcomes included the rates of sustained seizure response, sustained seizure freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events (AEs) and the incidence of AEs. Data were compared for patients treated with add-on BRV after 1-2 (early add-on) and ≥ 3 (late add-on) prior antiseizure medications. Results: A total of 1029 patients with focal epilepsy were included in the study, of whom 176 (17.1%) received BRV as early add-on treatment. The median daily dose of BRV at 12months was 125 (100-200) mg in the early add-on group and 200 (100-200) in the late add-on group (p
Published: 2022

4. Correction to: Adjunctive Brivaracetam in Focal Epilepsy: Real‑World Evidence from the BRIVAracetam add‑on First Italian netwoRk Study (BRIVAFIRST) (CNS Drugs, (2021), 35, 12, (1289-1301), 10.1007/s40263-021-00856-3)

Author: Lattanzi, S., Canafoglia, L., Canevini, M. P., Casciato, S., Chiesa, V., Dainese, F., De Maria, G., Didato, G., Falcicchio, G., Fanella, M., Ferlazzo, E., Fisco, G., Gangitano, M., Giallonardo, A. T., Giorgi, F. S., La Neve, A., Mecarelli, O., Montalenti, E., Piazza, F., Pulitano, P., Quarato, P. P., Ranzato, F., Rosati, E., Tassi, L., Di Bonaventura, C., Alicino, A., Ascoli, M., Assenza, G., Avorio, F., Badioni, V., Banfi, P., Bartolini, E., Basili, L. M., Belcastro, V., Beretta, S., Berto, I., Biggi, M., Billo, G., Boero, G., Bonanni, P., Bongorno, J., Brigo, F., Caggia, E., Cagnetti, C., Calvello, C., Irelli, E. C., Cesnik, E., Chianale, G., Ciampanelli, D., Ciuffini, R., Cocito, D., Colella, D., Contento, M., Costa, C., Cumbo, E., D'Aniello, A., Deleo, F., Difrancesco, J. C., Gennaro, G., Di Giacomo, R., Di Liberto, A., Domina, E., Donato, F., Dono, F., Durante, V., Elia, M., Estraneo, A., Evangelista, G., Faedda, M. T., Failli, Y., Fallica, E., Fattouch, J., Ferrari, A., Ferreri, F., Fonti, D., Fortunato, F., Foschi, N., Francavilla, T., Galli, R., Gazzina, S., Giuliano, L., Habetswallner, F., Izzi, F., Kassabian, B., Labate, A., Luisi, C., Magliani, M., Maira, G., Mari, L., Marino, D., Mascia, A., Mazzeo, A., Meletti, S., Morano, A., Nilo, A., Orlando, B., Paladin, F., Pascarella, M. G., Pastori, C., Pauletto, G., Peretti, A., Perri, G., Pezzella, M., Piccioli, M., Pignatta, P., Pilolli, N., Pisani, F., Pisani, L. R., Placidi, F., Pollicino, P., Porcella, V., Pradella, S., Puligheddu, M., Quadri, S., Quintas, R., Renna, R., Rossi, J., Rum, A., Salamone, E. M., Savastano, E., Sessa, M., Stokelj, D., Tartara, E., Tombini, M., Tumminelli, G., Ventura, M., Vigano, I., Viglietta, E., Vignoli, A., Villani, F., Zambrelli, E., and Zummo, L.
Published: 2021

5. THE EFFECTS OF RAPAMYCIN ON THE OCCURRENCE OF PRIONOIDS IN GLIOBLASTOMA MULTIFORME

Author: Ryskalin, L, Biagioni, F, Gesi, M, Ruffoli, R, Giorgi, F. S., Lenzi, P, and Forna, i. F.
Published: 2021

6. Correction to: Adjunctive Brivaracetam in Focal Epilepsy: Real‑World Evidence from the BRIVAracetam add‑on First Italian netwoRk Study (BRIVAFIRST) (CNS Drugs, (2021), 10.1007/s40263-021-00856-3)

Author: Lattanzi, S., Canafoglia, L., Canevini, M. P., Casciato, S., Chiesa, V., Dainese, F., De Maria, G., Didato, G., Falcicchio, G., Fanella, M., Ferlazzo, E., Fisco, G., Gangitano, M., Giallonardo, A. T., Giorgi, F. S., La Neve, A., Mecarelli, O., Montalenti, E., Piazza, F., Pulitano, P., Quarato, P. P., Ranzato, F., Rosati, E., Tassi, L., Di Bonaventura, C., Alicino, A., Ascoli, M., Assenza, G., Avorio, F., Badioni, V., Banfi, P., Bartolini, E., Basili, L. M., Belcastro, V., Beretta, S., Berto, I., Biggi, M., Billo, G., Boero, G., Bonanni, P., Bongorno, J., Brigo, F., Caggia, E., Cagnetti, C., Calvello, C., Irelli, E. C., Cesnik, E., Chianale, G., Ciampanelli, D., Ciuffini, R., Cocito, D., Colella, D., Contento, M., Costa, C., Cumbo, E., D'Aniello, A., Deleo, F., Difrancesco, J. C., Gennaro, G., Di Giacomo, R., Di Liberto, A., Domina, E., Donato, F., Dono, F., Durante, V., Elia, M., Estraneo, A., Evangelista, G., Faedda, M. T., Failli, Y., Fallica, E., Fattouch, J., Ferrari, A., Ferreri, F., Fonti, D., Fortunato, F., Foschi, N., Francavilla, T., Galli, R., Gazzina, S., Giuliano, L., Habetswallner, F., Izzi, F., Kassabian, B., Labate, A., Luisi, C., Magliani, M., Maira, G., Mari, L., Marino, D., Mascia, A., Mazzeo, A., Meletti, S., Morano, A., Nilo, A., Orlando, B., Paladin, F., Pascarella, M. G., Pastori, C., Pauletto, G., Peretti, A., Perri, G., Pezzella, M., Piccioli, M., Pignatta, P., Pilolli, N., Pisani, F., Pisani, L. R., Placidi, F., Pollicino, P., Porcella, V., Pradella, S., Puligheddu, M., Quadri, S., Quintas, R., Renna, R., Rossi, J., Rum, A., Salamone, E. M., Savastano, E., Sessa, M., Stokelj, D., Tartara, E., Tombini, M., Tumminelli, G., Ventura, M., Vigano, I., Viglietta, E., Vignoli, A., Villani, F., Zambrelli, E., and Zummo, L.
Published: 2021

7. Adjunctive Brivaracetam in Focal Epilepsy: Real-World Evidence from the BRIVAracetam add-on First Italian netwoRk STudy (BRIVAFIRST)

Author: Lattanzi, S., Canafoglia, L., Canevini, M. P., Casciato, S., Chiesa, V., Dainese, F., De Maria, G., Didato, G., Falcicchio, G., Fanella, M., Ferlazzo, E., Fisco, G., Gangitano, M., Giallonardo, A. T., Giorgi, F. S., La Neve, A., Mecarelli, O., Montalenti, E., Piazza, F., Pulitano, P., Quarato, P. P., Ranzato, F., Rosati, E., Tassi, L., Di Bonaventura, C., Alicino, A., Ascoli, M., Assenza, G., Avorio, F., Badioni, V., Banfi, P., Bartolini, E., Basili, L. M., Belcastro, V., Beretta, S., Berto, I., Biggi, M., Billo, G., Boero, G., Bonanni, P., Bongorno, J., Brigo, F., Caggia, E., Cagnetti, C., Calvello, C., Irelli, E. C., Cesnik, E., Chianale, G., Ciampanelli, D., Ciuffini, R., Cocito, D., Colella, D., Contento, M., Costa, C., Cumbo, E., D'Aniello, A., Deleo, F., Difrancesco, J. C., Di Gennaro, G., Di Giacomo, R., Di Liberto, A., Domina, E., Donato, F., Dono, F., Durante, V., Elia, M., Estraneo, A., Evangelista, G., Faedda, M. T., Failli, Y., Fallica, E., Fattouch, J., Ferrari, A., Ferreri, F., Fonti, D., Fortunato, F., Foschi, N., Francavilla, T., Galli, R., Gazzina, S., Giuliano, L., Habetswallner, F., Izzi, F., Kassabian, B., Labate, A., Luisi, C., Magliani, M., Maira, G., Mari, L., Marino, D., Mascia, A., Mazzeo, A., Meletti, S., Morano, A., Nilo, A., Orlando, B., Paladin, F., Pascarella, M. G., Pastori, C., Pauletto, G., Peretti, A., Perri, G., Pezzella, M., Piccioli, M., Pignatta, P., Pilolli, N., Pisani, F., Pisani, L. R., Placidi, F., Pollicino, P., Porcella, V., Pradella, S., Puligheddu, M., Quadri, S., Quintas, R., Renna, R., Rossi, J., Rum, A., Salamone, E. M., Savastano, E., Sessa, M., Stokelj, D., Tartara, E., Tombini, M., Tumminelli, G., Ventura, M., Vigano, I., Viglietta, E., Vignoli, A., Villani, F., Zambrelli, E., Zummo, L., Lattanzi S., Canafoglia L., Canevini M.P., Casciato S., Chiesa V., Dainese F., De Maria G., Didato G., Falcicchio G., Fanella M., Ferlazzo E., Fisco G., Gangitano M., Giallonardo A.T., Giorgi F.S., La Neve A., Mecarelli O., Montalenti E., Piazza F., Pulitano P., Quarato P.P., Ranzato F., Rosati E., Tassi L., and Di Bonaventura C.
Subjects: medicine.medical_specialty, business.industry, Context (language use), Brivaracetam, medicine.disease, Discontinuation, law.invention, Psychiatry and Mental health, Epilepsy, Randomized controlled trial, Tolerability, focal epilepsy, add-on therapy, seizure, law, Concomitant, Internal medicine, Medicine, Pharmacology (medical), Neurology (clinical), Levetiracetam, Original Research Article, business, medicine.drug
Abstract: Background: In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Studies performed in a naturalistic setting are a useful complement to characterize the drug profile. Objective: This multicentre study assessed the effectiveness and tolerability of adjunctive BRV in a large population of patients with focal epilepsy in the context of real-world clinical practice. Methods: The BRIVAFIRST (BRIVAracetam add-on First Italian netwoRk STudy) was a retrospective, multicentre study including adult patients prescribed adjunctive BRV. Patients with focal epilepsy and 12-month follow-up were considered. Main outcomes included the rates of seizure‐freedom, seizure response (≥50% reduction in baseline seizure frequency), and treatment discontinuation. The incidence of adverse events (AEs) was also considered. Analyses by levetiracetam (LEV) status and concomitant use of strong enzyme-inducing antiseizure medications (EiASMs) and sodium channel blockers (SCBs) were performed. Results: A total of 1029 patients with a median age of 45years (33–56) was included. At 12 months, 169 (16.4%) patients were seizure-free and 383 (37.2%) were seizure responders. The rate of seizure freedom was 22.3% in LEV-naive patients, 7.1% in patients with prior LEV use and discontinuation due to insufficient efficacy, and 31.2% in patients with prior LEV use and discontinuation due to AEs (p&nbsp
Published: 2021

8. The management of epilepsy in clinical practice: Do the timing and severity of the disease influence the priorities of patients and the caring physicians? Data from the EPINEEDS study

Author: Enia, G, Giussani, G, Bianchi, E, Mecarelli, O, Beghi, E, Pulitano, P, Cagnetti, C, Baldinelli, S, Lattanzi, S, La, N, Tappata, M, Francavilla, T, De Maria, G, Sofia, V, Giuliano, L, Mainieri, G, Fatuzzo, D, Belcastro, V, Elia, M, D'Orsi, G, Lalla, A, Salmaggi, A, Brigo, F, Magaudda, A, Pisani, F, Pisani, L, Raffaele, M, Cosenza, D, Villani, F, Quintas, R, Cervellione, R, Borroni, S, Meletti, S, Ferrarese, C, Barbella, G, Di Francesco, J, Bogliun, G, Beretta, S, Galimberti, C, Cantisani, T, Cecconi, M, Celani, M, Papetti, R, Giorgi, F, Aguglia, U, Gasparini, S, Ferlazzo, E, Manganotti, P, Crichiutti, G, Bravar, G, Enia G., Giussani G., Bianchi E., Mecarelli O., Beghi E., Pulitano P., Cagnetti C., Baldinelli S., Lattanzi S., La N. A., Tappata M., Francavilla T., De Maria G., Sofia V., Giuliano L., Mainieri G., Fatuzzo D., Belcastro V., Elia M., D'Orsi G., Lalla A., Salmaggi A., Brigo F., Magaudda A., Pisani F. G. S., Pisani L. R., Raffaele M., Cosenza D., Villani F. S., Quintas R. M. M., Cervellione R., Borroni S., Meletti S., Ferrarese C., Barbella G., Di Francesco J., Bogliun G., Beretta S., Galimberti C. A., Cantisani T. A., Cecconi M., Celani M. G., Papetti R., Giorgi F. S., Aguglia U., Gasparini S., Ferlazzo E., Manganotti P., Crichiutti G., Bravar G., Enia, G, Giussani, G, Bianchi, E, Mecarelli, O, Beghi, E, Pulitano, P, Cagnetti, C, Baldinelli, S, Lattanzi, S, La, N, Tappata, M, Francavilla, T, De Maria, G, Sofia, V, Giuliano, L, Mainieri, G, Fatuzzo, D, Belcastro, V, Elia, M, D'Orsi, G, Lalla, A, Salmaggi, A, Brigo, F, Magaudda, A, Pisani, F, Pisani, L, Raffaele, M, Cosenza, D, Villani, F, Quintas, R, Cervellione, R, Borroni, S, Meletti, S, Ferrarese, C, Barbella, G, Di Francesco, J, Bogliun, G, Beretta, S, Galimberti, C, Cantisani, T, Cecconi, M, Celani, M, Papetti, R, Giorgi, F, Aguglia, U, Gasparini, S, Ferlazzo, E, Manganotti, P, Crichiutti, G, Bravar, G, Enia G., Giussani G., Bianchi E., Mecarelli O., Beghi E., Pulitano P., Cagnetti C., Baldinelli S., Lattanzi S., La N. A., Tappata M., Francavilla T., De Maria G., Sofia V., Giuliano L., Mainieri G., Fatuzzo D., Belcastro V., Elia M., D'Orsi G., Lalla A., Salmaggi A., Brigo F., Magaudda A., Pisani F. G. S., Pisani L. R., Raffaele M., Cosenza D., Villani F. S., Quintas R. M. M., Cervellione R., Borroni S., Meletti S., Ferrarese C., Barbella G., Di Francesco J., Bogliun G., Beretta S., Galimberti C. A., Cantisani T. A., Cecconi M., Celani M. G., Papetti R., Giorgi F. S., Aguglia U., Gasparini S., Ferlazzo E., Manganotti P., Crichiutti G., and Bravar G.
Abstract: Objective: The objective of this study was to assess the priorities of patients with epilepsy and their caring physicians with reference to the timing and severity of the disease. Methods: This is a national survey in which patients with epilepsy followed in 21 Italian epilepsy centers, and their caring physicians were asked to fill anonymous questionnaires to collect data on different aspects of the disease and their needs and priorities in its management. The collected information included demographics, clinical profile and diagnosis, treatment and outcome of epilepsy. The questions were designed to understand the expectations of the patients and their caring physicians and verify the degree of concordance between patient and doctor. The study population was divided in six prognostic categories: (1) Newly diagnosed epilepsy; (2) Absence of seizures for at least 2 years; (3) Absence of seizures for at least 1 year or occasional seizures; (4) Nondrug-resistant recurrent seizures; (5) drug-resistant seizures; (6) surgical candidate. Results: Of the 787 patients enrolled, 432 were women and 355 men aged 15 to 88 years (median 41 years). Disease duration ranged from 6 months to 75 years. The sample included 53 patients with newly diagnosed epilepsy, 283 without seizures for at least 2 years, 162 seizure-free for at least 1 year or with occasional seizures, 123 with nondrug-resistant recurrent seizures, 128 with drug-resistant seizures, and 38 surgical candidates. Significant differences were found between patients and physicians in terms of priorities and needs with reference to the management of the disease. While physicians tend to prioritize the information on the diagnosis and treatment of epilepsy depending on timing and severity, patients focus on the search of the cause, the side effects of drugs, and the effects of any new treatment on the control of seizures regardless of the prognostic category. In addition, physicians tend to undervalue the communication of
Published: 2021

9. Partial sleep deprivation in patients with focal epilepsy: effect on sleep macrostructure and cyclic alternating pattern: P972

Author: Carnicelli, L., Caciagli, L., Maestri, M., Giorgi, F. S., Guida, M., Di Coscio, E., Bonuccelli, U., and Bonanni, E.
Published: 2014

10. Brain Hemodynamic Intermediate Phenotype Links Vitamin B12 to Cognitive Profile of Healthy and Mild Cognitive Impaired Subjects

Author: Cecchetti L., Lettieri G., Handjaras G., Leo A., Ricciardi E., Pietrini P., Pellegrini S., Andreassi M. G., Angelucci A., Baldacci F., Baroncelli L., Begenisic T., Bellinvia P. F., Biagi L., Bonaccorsi J., Bonanni E., Borghini A., Braschi C., Broccardi M., Caleo M., Carlesi C., Carnicelli L., Cartoni G., Cenni M. C., Ceravolo R., Chico L., Cioni G., Costa M., D'Ascanio P., De Nes M., Di Coscio E., Di Galante M., di Lascio N., Faita F., Falorni I., Faraguna U., Fenu A., Fortunato L., Franco R., Gargiulo R., Giorgi F. S., Iannarella R., Iofrida C., Kusmic C., Limongi F., Maestri M., Maffei M., Maggi S., Mainardi M., Mammana L., Marabotti A., Mariotti V., Melissari E., Mercuri A., Molinaro S., Narducci R., Navarra T., Noale M., Pagni C., Palumbo S., Pasquariello R., Pizzorusso T., Poli A., Retico A., Rota G., Sale A., Scabia G., Scali M., Scelfo D., Siciliano G., Tonacci A., Tosetti M., Turchi S., Volpi L., Cecchetti, L., Lettieri, G., Handjaras, G., Leo, A., Ricciardi, E., Pietrini, P., Pellegrini, S., Andreassi, M. G., Angelucci, A., Baldacci, F., Baroncelli, L., Begenisic, T., Bellinvia, P. F., Biagi, L., Bonaccorsi, J., Bonanni, E., Borghini, A., Braschi, C., Broccardi, M., Caleo, M., Carlesi, C., Carnicelli, L., Cartoni, G., Cenni, M. C., Ceravolo, R., Chico, L., Cioni, G., Costa, M., D'Ascanio, P., De Nes, M., Di Coscio, E., Di Galante, M., di Lascio, N., Faita, F., Falorni, I., Faraguna, U., Fenu, A., Fortunato, L., Franco, R., Gargiulo, R., Giorgi, F. S., Iannarella, R., Iofrida, C., Kusmic, C., Limongi, F., Maestri, M., Maffei, M., Maggi, S., Mainardi, M., Mammana, L., Marabotti, A., Mariotti, V., Melissari, E., Mercuri, A., Molinaro, S., Narducci, R., Navarra, T., Noale, M., Pagni, C., Palumbo, S., Pasquariello, R., Pizzorusso, T., Poli, A., Retico, A., Rota, G., Sale, A., Scabia, G., Scali, M., Scelfo, D., Siciliano, G., Tonacci, A., Tosetti, M., Turchi, S., and Volpi, L.
Subjects: Vitamin, Male, medicine.medical_specialty, Article Subject, Homocysteine, Brain activity and meditation, Longitudinal Studie, Settore BIO/09 - Fisiologia, lcsh:RC321-571, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cognition, Neuroimaging, Internal medicine, medicine, Humans, Cognitive Dysfunction, Vitamin B12, Hemodynamic, Longitudinal Studies, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Anterior cingulate cortex, 030304 developmental biology, Aged, Aged, 80 and over, 0303 health sciences, business.industry, Neuropsychology, Hemodynamics, Brain, Vitamin B 12, medicine.anatomical_structure, Endocrinology, Phenotype, Neurology, chemistry, Female, Neurology (clinical), Cohort Studie, business, 030217 neurology & neurosurgery, Human, Research Article
Abstract: Vitamin B12, folate, and homocysteine are implicated in pivotal neurodegenerative mechanisms and partake in elders' mental decline. Findings on the association between vitamin-related biochemistry and cognitive abilities suggest that the structural and functional properties of the brain may represent an intermediate biomarker linking vitamin concentrations to cognition. Despite this, no previous study directly investigated whether vitamin B12, folate, and homocysteine levels are sufficient to explain individual neuropsychological profiles or, alternatively, whether the activity of brain regions modulated by these compounds better predicts cognition in elders. Here, we measured the relationship between vitamin blood concentrations, scores at seventeen neuropsychological tests, and brain activity of sixty-five elders spanning from normal to Mild Cognitive Impairment. We then evaluated whether task-related brain responses represent an intermediate phenotype, providing a better prediction of subjects' neuropsychological scores, as compared to the one obtained considering blood biochemistry only. We found that the hemodynamic activity of the right dorsal anterior cingulate cortex was positively associated (p value < 0 05 cluster corrected) with vitamin B12 concentrations, suggesting that elders with higher B12 levels had a more pronounced recruitment of this salience network region. Crucially, the activity of this area significantly predicted subjects' visual search and attention abilities (p value = 0 0023), whereas B12 levels per se failed to do so. Our results demonstrate that the relationship between blood biochemistry and elders' cognitive abilities is revealed when brain activity is included into the equation, thus highlighting the role of brain imaging as intermediate phenotype. Vitamin B12, folate, and homocysteine are implicated in pivotal neurodegenerative mechanisms and partake in elders' mental decline. Findings on the association between vitamin-related biochemistry and cognitive abilities suggest that the structural and functional properties of the brain may represent an intermediate biomarker linking vitamin concentrations to cognition. Despite this, no previous study directly investigated whether vitamin B12, folate, and homocysteine levels are sufficient to explain individual neuropsychological profiles or, alternatively, whether the activity of brain regions modulated by these compounds better predicts cognition in elders. Here, we measured the relationship between vitamin blood concentrations, scores at seventeen neuropsychological tests, and brain activity of sixty-five elders spanning from normal to Mild Cognitive Impairment. We then evaluated whether task-related brain responses represent an intermediate phenotype, providing a better prediction of subjects' neuropsychological scores, as compared to the one obtained considering blood biochemistry only. We found that the hemodynamic activity of the right dorsal anterior cingulate cortex was positively associated (p value < 0 05 cluster corrected) with vitamin B12 concentrations, suggesting that elders with higher B12 levels had a more pronounced recruitment of this salience network region. Crucially, the activity of this area significantly predicted subjects' visual search and attention abilities (p value = 0 0023), whereas B12 levels per se failed to do so. Our results demonstrate that the relationship between blood biochemistry and elders' cognitive abilities is revealed when brain activity is included into the equation, thus highlighting the role of brain imaging as intermediate phenotype.
Published: 2019

11. Differential default mode network trajectories in asymptomatic individuals at risk for Alzheimer's disease

Author: Chiesa P. A., Cavedo E., Vergallo A., Lista S., Potier M. -C., Habert M. -O., Dubois B., Thiebaut de Schotten M., Hampel H., Audrain C., Auffret A., Bakardjian H., Baldacci F., Batrancourt B., Benakki I., Benali H., Bertin H., Bertrand A., Boukadida L., Cacciamani F., Causse V., Cherif Touil S., Colliot O., Dalla Barba G., Depaulis M., Dos Santos A., Dubois M., Epelbaum S., Fontaine B., Francisque H., Gagliardi G., Genin A., Genthon R., Glasman P., Gombert F., Habert M. O., Hewa H., Houot M., Jungalee N., Kas A., Kilani M., La Corte V., Le Roy F., Lehericy S., Letondor C., Levy M., Lowrey M., Ly J., Makiese O., Masetti I., Mendes A., Metzinger C., Michon A., Mochel F., Nait Arab R., Nyasse F., Perrin C., Poirier F., Poisson C., Potier M. C., Ratovohery S., Revillon M., Rojkova K., Santos-Andrade K., Schindler R., Servera M. C., Seux L., Simon V., Skovronsky D., Uspenskaya O., Vlaincu M., Aguilar L. F., Babiloni C., Benda N., Black K. L., Bokde A. L. W., Bonuccelli U., Broich K., Cacciola F., Castrillo J., Ceravolo R., Corvol J. -C., Claudio Cuello A., Cummings J. L., Depypere H., Duggento A., Durrleman S., Escott-Price V., Federoff H., Teresa Ferretti M., Fiandaca M., Frank R. A., Garaci F., Geerts H., George N., Giorgi F. S., Graziani M., Haberkamp M., Herholz K., Karran E., Kim S. H., Koronyo Y., Koronyo-Hamaoui M., Lamari F., Langevin T., Lorenceau J., Mango D., Mapstone M., Neri C., Nistico R., O'Bryant S. E., Palermo G., Perry G., Ritchie C., Rossi S., Saidi A., Santarnecchi E., Schneider L. S., Sporns O., Toschi N., Verdooner S. R., Villain N., Welikovitch L. A., Woodcock J., Younesi E., Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neuroradiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Treat SVD, Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), sans affiliation, Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Sorbonne Université (SU), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Sorbonne Université (SU)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de médecine nucléaire [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre des Maladies Cognitives et Comportementales [Paris], Fraunhofer Center for Assistive Information and Communication Solutions [Porto] (Fraunhofer AICOS), Fraunhofer (Fraunhofer-Gesellschaft), Ariana Pharmaceuticals, McGill University = Université McGill [Montréal, Canada], Universidad Autonoma de Madrid (UAM), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], University of Pisa - Università di Pisa, Federal Institute of Drugs and Medical Devices [Bonn], Discipline of Psychiatry [Dublin], School of Medicine [Dublin], Trinity College Dublin-Trinity College Dublin, Universita degli Studi di Messina, University of Catania [Italy], University of Cambridge [UK] (CAM), Lou Ruvo Center for Brain Health [Las Vegas], Cleveland Clinic, Università degli Studi di Roma Tor Vergata [Roma], University of Pavia, Cardiff University, Universität Zürich [Zürich] = University of Zurich (UZH), University of California [Irvine] (UCI), University of California, Siemens Healthineers, Digital Services, Digital Technology and Innovation, In Silico Biosciences (ISB), Abdus Salam International Centre for Theoretical Physics [Trieste] (ICTP), University of California [San Francisco] (UCSF), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Manchester [Manchester], National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Abbvie Inc. [North Chicago], Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, University of Britsh Columbia [Vancouver], Cedars-Sinai Medical Center, Functional Neuromodulation, CIBER de Enfermedades Raras (CIBERER), Institut de la Vision, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Brain Research Institute [Rome, Italy] (EBRI), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institute for Aging and Alzheimer’s Disease Research [Fort Worth] (IAADR), University of North Texas Health Science Center [Fort Worth], University of Auckland [Auckland], University of Edinburgh, Università degli Studi di Siena = University of Siena (UNISI), Harvard Medical School [Boston] (HMS), Keck School of Medicine [Los Angeles], University of Southern California (USC), Indiana State University, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS), NeuroVision Imaging, Fondation pour la Recherche sur Alzheimer, Center for Drug Evaluation and Research (CDER), European Society for Translational Medicine (EUSTM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service d'Explorations Fonctionnelles Neurologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de médecine nucléaire [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Fraunhofer AICOS [Porto], McGill University, Sapienza University [Rome], University of Zürich [Zürich] (UZH), Università degli Studi di Roma 'La Sapienza' [Rome], CHU Pitié-Salpêtrière [APHP], Service de neuro-radiologie [CHU Pitié-Salpêtrière], Università degli Studi di Siena (UNISI), Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Service de Médecine nucléaire [CHU Pitié-Salpétrière], Universidad Autónoma de Madrid (UAM), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Imagerie Biomédicale [Paris] (LIB), Sans affiliation, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Università degli Studi di Messina = University of Messina (UniMe), Università degli Studi di Pavia = University of Pavia (UNIPV), University of California [Irvine] (UC Irvine), University of California (UC), University of California [San Francisco] (UC San Francisco), University of British Columbia [Vancouver], Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Chiesa, P. A., Cavedo, E., Vergallo, A., Lista, S., Potier, M. -C., Habert, M. -O., Dubois, B., Thiebaut de Schotten, M., Hampel, H., Audrain, C., Auffret, A., Bakardjian, H., Baldacci, F., Batrancourt, B., Benakki, I., Benali, H., Bertin, H., Bertrand, A., Boukadida, L., Cacciamani, F., Causse, V., Cherif Touil, S., Colliot, O., Dalla Barba, G., Depaulis, M., Dos Santos, A., Dubois, M., Epelbaum, S., Fontaine, B., Francisque, H., Gagliardi, G., Genin, A., Genthon, R., Glasman, P., Gombert, F., Habert, M. O., Hewa, H., Houot, M., Jungalee, N., Kas, A., Kilani, M., La Corte, V., Le Roy, F., Lehericy, S., Letondor, C., Levy, M., Lowrey, M., Ly, J., Makiese, O., Masetti, I., Mendes, A., Metzinger, C., Michon, A., Mochel, F., Nait Arab, R., Nyasse, F., Perrin, C., Poirier, F., Poisson, C., Potier, M. C., Ratovohery, S., Revillon, M., Rojkova, K., Santos-Andrade, K., Schindler, R., Servera, M. C., Seux, L., Simon, V., Skovronsky, D., Uspenskaya, O., Vlaincu, M., Aguilar, L. F., Babiloni, C., Benda, N., Black, K. L., Bokde, A. L. W., Bonuccelli, U., Broich, K., Cacciola, F., Castrillo, J., Ceravolo, R., Corvol, J. -C., Claudio Cuello, A., Cummings, J. L., Depypere, H., Duggento, A., Durrleman, S., Escott-Price, V., Federoff, H., Teresa Ferretti, M., Fiandaca, M., Frank, R. A., Garaci, F., Geerts, H., George, N., Giorgi, F. S., Graziani, M., Haberkamp, M., Herholz, K., Karran, E., Kim, S. H., Koronyo, Y., Koronyo-Hamaoui, M., Lamari, F., Langevin, T., Lorenceau, J., Mango, D., Mapstone, M., Neri, C., Nistico, R., O'Bryant, S. E., Palermo, G., Perry, G., Ritchie, C., Rossi, S., Saidi, A., Santarnecchi, E., Schneider, L. S., Sporns, O., Toschi, N., Verdooner, S. R., Villain, N., Welikovitch, L. A., Woodcock, J., Younesi, E., and Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Apolipoprotein E, Epidemiology, Brain activity and meditation, Precuneus, Disease, Neuropsychological Tests, Hippocampus, Cohort Studies, [SCCO]Cognitive science, 0302 clinical medicine, Medicine, Longitudinal Studies, Default mode network, ComputingMilieux_MISCELLANEOUS, Brain Mapping, Subjective memory complaints, Brain functional dynamic, Health Policy, Precision medicine, fMRI, Settore BIO/14, Brain, Brain functional dynamics, Alzheimer's disease, Magnetic Resonance Imaging, Temporal Lobe, Frontal Lobe, Psychiatry and Mental health, medicine.anatomical_structure, Cohort, Biomarker (medicine), Female, Amyloid, 03 medical and health sciences, Cellular and Molecular Neuroscience, Apolipoproteins E, Developmental Neuroscience, Alzheimer Disease, Humans, Aged, Resting state fMRI, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, 030104 developmental biology, Neurology (clinical), Geriatrics and Gerontology, business, Neuroscience, 030217 neurology & neurosurgery
Abstract: Introduction The longitudinal trajectories of functional brain dynamics and the impact of genetic risk factors in individuals at risk for Alzheimer's disease are poorly understood. Methods In a large-scale monocentric cohort of 224 amyloid stratified individuals at risk for Alzheimer's disease, default mode network (DMN) resting state functional connectivity (FC) was investigated between two serial time points across 2 years. Results Widespread DMN FC changes were shown in frontal and posterior areas, as well as in the right hippocampus. There were no cross-sectional differences, however, apolipoprotein E e4 (APOE e4) carriers demonstrated slower increase in FC in frontal lobes. There was no impact of individual brain amyloid load status. Discussion For the first time, we demonstrated that the pleiotropic biological effect of the APOE e4 allele impacts the dynamic trajectory of the DMN during aging. Dynamic functional biomarkers may become useful surrogate outcomes for the development of preclinical targeted therapeutic interventions.
Published: 2019

12. Effects of combined training on neuropsychiatric symptoms and quality of life in patients with cognitive decline

Author: Cintoli, S., Radicchi, C., Noale, M., Maggi, S., Meucci, G., Tognoni, G., Bonuccelli, U., Sale, A., Berardi, N., Maffei, L., Picano, E., Andreassi, M. G., Angelucci, A., Baldacci, F., Baroncelli, L., Begenisic, T., Bellinvia, P. F., Biagi, L., Bonaccorsi, J., Bonanni, E., Borghini, A., Braschi, C., Broccardi, M., Bruno, R. M., Caleo, M., Carlesi, C., Carnicelli, L., Cartoni, G., Cecchetti, L., Cenni, M. C., Ceravolo, R., Chico, L., Cioni, G., Coscia, M., Costa, M., D'Angelo, G., D'Ascanio, P., Denes, M., Delturco, S., Dicoscio, E., Digalante, M., Dilascio, N., Faita, F., Falorni, I., Faraguna, U., Fenu, A., Fortunato, L., Franco, R., Gargani, L., Gargiulo, R., Ghiadoni, L., Giorgi, F. S., Iannarella, R., Iofrida, C., Kusmic, C., Limongi, F., Maestri, M., Maffei, M., Mainardi, M., Mammana, L., Marabotti, A., Mariotti, V., Melissari, E., Mercuri, A., Micera, S., Molinaro, S., Narducci, R., Navarra, T., Pagni, C., Palumbo, S., Pasquariello, R., Pellegrini, S., Pietrini, P., Pizzorusso, T., Poli, A., Pratali, L., Retico, A., Ricciardi, E., Rota, G., Sbrana, S., Scabia, G., Scali, M., Scelfo, D., Sicari, R., Siciliano, G., Stea, F., Taddei, S., Tonacci, A., Tosetti, M., Turchi, S., Volpi, L., Cintoli, S., Radicchi, C., Noale, M., Maggi, S., Meucci, G., Tognoni, G., Bonuccelli, U., Sale, A., Berardi, N., Maffei, L., Picano, E., Andreassi, M. G., Angelucci, A., Baldacci, F., Baroncelli, L., Begenisic, T., Bellinvia, P. F., Biagi, L., Bonaccorsi, J., Bonanni, E., Borghini, A., Braschi, C., Broccardi, M., Bruno, R. M., Caleo, M., Carlesi, C., Carnicelli, L., Cartoni, G., Cecchetti, L., Cenni, M. C., Ceravolo, R., Chico, L., Cioni, G., Coscia, M., Costa, M., D'Angelo, G., D'Ascanio, P., Denes, M., Delturco, S., Dicoscio, E., Digalante, M., Dilascio, N., Faita, F., Falorni, I., Faraguna, U., Fenu, A., Fortunato, L., Franco, R., Gargani, L., Gargiulo, R., Ghiadoni, L., Giorgi, F. S., Iannarella, R., Iofrida, C., Kusmic, C., Limongi, F., Maestri, M., Maffei, M., Mainardi, M., Mammana, L., Marabotti, A., Mariotti, V., Melissari, E., Mercuri, A., Micera, S., Molinaro, S., Narducci, R., Navarra, T., Pagni, C., Palumbo, S., Pasquariello, R., Pellegrini, S., Pietrini, P., Pizzorusso, T., Poli, A., Pratali, L., Retico, A., Ricciardi, E., Rota, G., Sbrana, S., Scabia, G., Scali, M., Scelfo, D., Sicari, R., Siciliano, G., Stea, F., Taddei, S., Tonacci, A., Tosetti, M., Turchi, S., and Volpi, L.
Subjects: Quality of life, medicine.medical_specialty, Aging, education, Psychological intervention, Neuropsychiatric symptom, Disease, Neuropsychological Tests, Settore BIO/09 - Fisiologia, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, mental disorders, Medicine, Dementia, Humans, Mild cognitive impairment, Neuropsychiatric symptoms, Non-pharmacological interventions, Physical and cognitive training, In patient, Cognitive Dysfunction, 030212 general & internal medicine, Cognitive decline, Aged, business.industry, Non-pharmacological intervention, Cognition, medicine.disease, Cognitive training, humanities, Physical therapy, Neuropsychological Test, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, Human
Abstract: Background and aims: Cognitive impairments associated with aging and dementia are major sources of neuropsychiatric symptoms (NPs) and deterioration in quality of life (QoL). Preventive measures to both reduce disease and improve QoL in those affected are increasingly targeting individuals with mild cognitive impairment (MCI) at early disease stage. However, NPs and QoL outcomes are too commonly overlooked in intervention trials. The purpose of this study was to test the effects of physical and cognitive training on NPs and QoL in MCI. Methods: Baseline data from an MCI court (N = 93, mean age 74.9 ± 4.7) enrolled in the Train the Brain (TtB) study were collected. Subjects were randomized in two groups: a group participated to a cognitive and physical training program, while the other sticked to usual standard care. Both groups underwent a follow-up re-evaluation after 7months from baseline. NPs were assessed using the Neuropsychiatric Inventory (NPI) and QoL was assessed using Quality of Life-Alzheimer’s Disease (QOL-AD) scale. Results: After 7months of training, training group exhibited a significant reduction of NPs and a significant increase in QOL-AD with respect to no-training group (p = 0.0155, p = 0.0013, respectively). Our preliminary results suggest that a combined training can reduce NPs and improve QoL. Conclusions: Measuring QoL outcomes is a potentially important factor in ensuring that a person with cognitive deficits can ‘live well’ with pathology. Future data from non-pharmacological interventions, with a larger sample and a longer follow-up period, could confirm the results and the possible implications for such prevention strategies for early cognitive decline. Background and aims: Cognitive impairments associated with aging and dementia are major sources of neuropsychiatric symptoms (NPs) and deterioration in quality of life (QoL). Preventive measures to both reduce disease and improve QoL in those affected are increasingly targeting individuals with mild cognitive impairment (MCI) at early disease stage. However, NPs and QoL outcomes are too commonly overlooked in intervention trials. The purpose of this study was to test the effects of physical and cognitive training on NPs and QoL in MCI. Methods: Baseline data from an MCI court (N = 93, mean age 74.9 ± 4.7) enrolled in the Train the Brain (TtB) study were collected. Subjects were randomized in two groups: a group participated to a cognitive and physical training program, while the other sticked to usual standard care. Both groups underwent a follow-up re-evaluation after 7 months from baseline. NPs were assessed using the Neuropsychiatric Inventory (NPI) and QoL was assessed using Quality of Life-Alzheimer’s Disease (QOL-AD) scale. Results: After 7 months of training, training group exhibited a significant reduction of NPs and a significant increase in QOL-AD with respect to no-training group (p = 0.0155, p = 0.0013, respectively). Our preliminary results suggest that a combined training can reduce NPs and improve QoL. Conclusions: Measuring QoL outcomes is a potentially important factor in ensuring that a person with cognitive deficits can ‘live well’ with pathology. Future data from non-pharmacological interventions, with a larger sample and a longer follow-up period, could confirm the results and the possible implications for such prevention strategies for early cognitive decline.
Published: 2019

13. Age and sex impact plasma NFL and t-Tau trajectories in individuals with subjective memory complaints: a 3-year follow-up study

Author: Baldacci, F., Lista, S., Manca, M. L., Chiesa, P. A., Cavedo, E., Lemercier, P., Zetterberg, H., Blennow, K., Habert, M. -O., Potier, M. C., Dubois, B., Vergallo, A., Hampel, H., Bakardjian, H., Benali, H., Bertin, H., Bonheur, J., Boukadida, L., Boukerrou, N., Chiesa, P., Colliot, O., Dubois, M., Epelbaum, S., Gagliardi, G., Genthon, R., Houot, M., Kas, A., Lamari, F., Levy, M., Metzinger, C., Mochel, F., Nyasse, F., Poisson, C., Potier, M. -C., Revillon, M., Santos, A., Andrade, K. S., Sole, M., Surtee, M., de Schotten, M. T., Younsi, N., Afshar, M., Aguilar, L. F., Akman-Anderson, L., Arenas, J., Avila, J., Babiloni, C., Batrla, R., Benda, N., Black, K. L., Bokde, A. L. W., Bonuccelli, U., Broich, K., Cacciola, F., Caraci, F., Caruso, G., Castrillo, J., Ceravolo, R., Corbo, M., Corvol, J. -C., Claudio, A., Cummings, J. L., Depypere, H., Duggento, A., Emanuele, E., Escott-Price, V., Federoff, H., Ferretti, M. T., Fiandaca, M., Frank, R. A., Garaci, F., Geerts, H., Giacobini, E., Giorgi, F. S., Goetzl, E. J., Graziani, M., Haberkamp, M., Hanisch, B., Herholz, K., Hernandez, F., Imbimbo, B. P., Kapogiannis, D., Karran, E., Kiddle, S. J., Kim, S. H., Koronyo, Y., Koronyo-Hamaoui, M., Langevin, T., Lehericy, S., Llavero, F., Lorenceau, J., Lucia, A., Mango, D., Mapstone, M., Neri, C., Nistico, R., O'Bryant, S. E., Palermo, G., Perry, G., Ritchie, C., Rossi, S., Saidi, A., Santarnecchi, E., Schneider, L. S., Sporns, O., Toschi, N., Valenzuela, P. L., Vellas, B., Verdooner, S. R., Villain, N., Virecoulon Giudici, K., Watling, M., Welikovitch, L. A., Woodcock, J., Younesi, E., Zugaza, J. L., Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Pisa - Università di Pisa, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Sorbonne Université (SU), Sahlgrenska Academy at University of Gothenburg [Göteborg], University College of London [London] (UCL), UK Dementia Research Institute (UK DRI), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de médecine nucléaire [CHU Pitié-Salpétrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, BIOMARKER, 0301 basic medicine, Oncology, Aging, Neurology, [SDV]Life Sciences [q-bio], Disease, Neurodegenerative, Alzheimer's Disease, Medical and Health Sciences, lcsh:RC346-429, MESH: Cognitive Dysfunction, Alzheimer’s disease, Biomarkers, Mild cognitive impairment, Neurofilament light chain, Subjective memory complainers, Tau, 0302 clinical medicine, Neurofilament Proteins, Medicine and Health Sciences, BRAIN, MESH: Neurofilament Proteins, RISK, Settore FIS/07, NEURODEGENERATION, Cognition, ASSOCIATION, MESH: Follow-Up Studies, Alzheimer's disease, MESH: Amyloid beta-Peptides, MESH: tau Proteins, ALZHEIMERS-DISEASE, POSITIVITY, Neurological, Cohort, Biomarker (medicine), Female, medicine.medical_specialty, Cognitive Neuroscience, tau Proteins, Subjective, Affect (psychology), VALIDATION, lcsh:RC321-571, subjective memory complainers, mild cognitive impairment, biomarkers, s disease, 03 medical and health sciences, memory complainers, Clinical Research, Alzheimer Disease, Internal medicine, NEUROFILAMENT LIGHT-CHAIN, Acquired Cognitive Impairment, medicine, Humans, Cognitive Dysfunction, Vitamin B12, Allele, Alzheimer&#8217, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, lcsh:Neurology. Diseases of the nervous system, Amyloid beta-Peptides, MESH: Humans, business.industry, Research, Prevention, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer Precision Medicine Initiative, COGNITIVE IMPAIRMENT, MESH: Male, Brain Disorders, 030104 developmental biology, MESH: Biomarkers, Dementia, Neurology (clinical), business, INSIGHT-preAD study group, MESH: Female, MESH: Alzheimer Disease, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: Background Plasma neurofilament light (NFL) and total Tau (t-Tau) proteins are candidate biomarkers for early stages of Alzheimer’s disease (AD). The impact of biological factors on their plasma concentrations in individuals with subjective memory complaints (SMC) has been poorly explored. We longitudinally investigate the effect of sex, age, APOE ε4 allele, comorbidities, brain amyloid-β (Aβ) burden, and cognitive scores on plasma NFL and t-Tau concentrations in cognitively healthy individuals with SMC, a condition associated with AD development. Methods Three hundred sixteen and 79 individuals, respectively, have baseline and three-time point assessments (at baseline, 1-year, and 3-year follow-up) of the two biomarkers. Plasma biomarkers were measured with an ultrasensitive assay in a mono-center cohort (INSIGHT-preAD study). Results We show an effect of age on plasma NFL, with women having a higher increase of plasma t-Tau concentrations compared to men, over time. The APOE ε4 allele does not affect the biomarker concentrations while plasma vitamin B12 deficiency is associated with higher plasma t-Tau concentrations. Both biomarkers are correlated and increase over time. Baseline NFL is related to the rate of Aβ deposition at 2-year follow-up in the left-posterior cingulate and the inferior parietal gyri. Baseline plasma NFL and the rate of change of plasma t-Tau are inversely associated with cognitive score. Conclusion We find that plasma NFL and t-Tau longitudinal trajectories are affected by age and female sex, respectively, in SMC individuals. Exploring the influence of biological variables on AD biomarkers is crucial for their clinical validation in blood.
Published: 2020

14. β-Secretase1 biological markers for Alzheimer’s disease: state-of-art of validation and qualification

Author: Hampel, H., Lista, S., Vanmechelen, E., Zetterberg, H., Giorgi, F. S., Galgani, A., Blennow, K., Caraci, F., Das, B., Yan, R., Vergallo, A., Aguilar, L. F., Akman-Anderson, L., Arenas, J., Avila, J., Babiloni, C., Baldacci, F., Batrla, R., Benda, N., Black, K. L., Bokde, A. L. W., Bonuccelli, U., Broich, K., Cacciola, F., Caruso, G., Castrillo, J., Cavedo, E., Ceravolo, R., Chiesa, P. A., Corbo, M., Corvol, J. -C., Cuello, A. C., Cummings, J. L., Depypere, H., Dubois, B., Duggento, A., Emanuele, E., Escott-Price, V., Federoff, H., Ferretti, M. T., Fiandaca, M., Frank, R. A., Garaci, F., Geerts, H., Giacobini, E., Goetzl, E. J., Graziani, M., Haberkamp, M., Habert, M. -O., Hanisch, B., Herholz, K., Hernandez, F., Imbimbo, B. P., Kapogiannis, D., Karran, E., Kiddle, S. J., Kim, S. H., Koronyo, Y., Koronyo-Hamaoui, M., Langevin, T., Lehericy, S., Lemercier, P., Llavero, F., Lorenceau, J., Lucia, A., Mango, D., Mapstone, M., Neri, C., Nistico, R., O'Bryant, S. E., Palermo, G., Perry, G., Ritchie, C., Rossi, S., Saidi, A., Santarnecchi, E., Schneider, L. S., Sporns, O., Toschi, N., Valenzuela, P. L., Vellas, B., Verdooner, S. R., Villain, N., Virecoulon Giudici, K., Watling, M., Welikovitch, L. A., Woodcock, J., Younesi, E., and Zugaza, J. L.
Subjects: BIOMARKER, 0301 basic medicine, Aging, Neurology, Fluid biomarkers, Axonal damage, context of use, Review, Alzheimer’s disease, Amyloid-β pathway, BACE1, clinical trials, fluid biomarkers, neurodegeneration, Disease, Neurodegenerative, Bioinformatics, Medical and Health Sciences, lcsh:RC346-429, Clinical trials, 0302 clinical medicine, PP-BETA, Medicine and Health Sciences, Aspartic Acid Endopeptidases, Context of use, Neurodegeneration, Amyloid Precursor Protein Secretases, Amyloid beta-Peptides, Biomarkers, Humans, Alzheimer Disease, RISK, screening and diagnosis, CORRELATE, Settore FIS/07, AMYLOID-PRECURSOR PROTEIN, Alzheimer's disease, Detection, Neurological, State of art, Biomarker (medicine), EXPRESSION, medicine.medical_specialty, Cognitive Neuroscience, lcsh:RC321-571, 03 medical and health sciences, CEREBROSPINAL-FLUID, Clinical Research, BETA-SECRETASE BACE1, mental disorders, Acquired Cognitive Impairment, medicine, Adverse effect, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, lcsh:Neurology. Diseases of the nervous system, Mechanism (biology), business.industry, Prevention, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Amyloid-beta pathway, medicine.disease, Brain Disorders, 4.1 Discovery and preclinical testing of markers and technologies, Clinical trial, Good Health and Well Being, 030104 developmental biology, Dementia, Alzheimer’s Precision Medicine Initiative, Neurology (clinical), TAU, business, 030217 neurology & neurosurgery, GENERATION
Abstract: β-Secretase1 (BACE1) protein concentrations and rates of enzyme activity, analyzed in human bodily fluids, are promising candidate biological markers for guidance in clinical trials investigating BACE1 inhibitors to halt or delay the dysregulation of the amyloid-β pathway in Alzheimer’s disease (AD). A robust body of evidence demonstrates an association between cerebrospinal fluid/blood BACE1 biomarkers and core pathophysiological mechanisms of AD, such as brain protein misfolding and aggregration, neurodegeneration, and synaptic dysfunction.In pharmacological trials, BACE1 candidate biomarkers may be applied to a wide set of contexts of use (CoU), including proof of mechanism, dose-finding, response and toxicity dose estimation. For clinical CoU, BACE1 biomarkers show good performance for prognosis and disease prediction.The roadmap toward validation and qualification of BACE1 biomarkers requires standardized pre-analytical and analytical protocols to reduce inter-site variance that may have contributed to inconsistent results.BACE1 biomarker-drug co-development programs, including biomarker-guided outcomes and endpoints, may support the identification of sub-populations with a higher probability to benefit from BACE1 inhibitors with a reduced risk of adverse effects, in line with the evolving precision medicine paradigm.
Published: 2020

15. The management of epilepsy in clinical practice: Do the needs manifested by the patients correspond to the priorities of the caring physicians? Findings from the EPINEEDS Study

Author: Giussani, G, Enia, G, Bianchi, E, Mecarelli, O, Beghi, E, Pulitano, P, Cagnetti, C, Baldinelli, S, La Neve, A, Tappata, M, Francavilla, T, De Maria, G, Sofia, V, Giuliano, L, Mainieri, G, Fatuzzo, D, Belcastro, V, Elia, M, D'Orsi, G, Lalla, A, Salmaggi, A, Brigo, F, Magaudda, A, Pisani, F, Galletta, S, Pisani, L, Raffaele, M, Cosenza, D, Villani, F, Quintas, R, Cervellione, R, Borroni, S, Meletti, S, Ferrarese, C, Barbella, G, Di Francesco, J, Bogliun, G, Beretta, S, Galimberti, C, Cantisani, T, Cecconi, M, Celani, M, Papetti, R, Giorgi, F, Aguglia, U, Gasparini, S, Ferlazzo, E, Manganotti, P, Crichiutti, G, Bravar, G, Giussani G., Enia G., Bianchi E., Mecarelli O., Beghi E., Pulitano P., Cagnetti C., Baldinelli S., La Neve A., Tappata M., Francavilla T., De Maria G., Sofia V., Giuliano L., Mainieri G., Fatuzzo D., Belcastro V., Elia M., D'Orsi G., Lalla A., Salmaggi A., Brigo F., Magaudda A., Pisani F., Galletta S., Pisani L. R., Raffaele M., Cosenza D., Villani F. S., Quintas R. M. M., Cervellione R., Borroni S., Meletti S., Ferrarese C., Barbella G., Di Francesco J., Bogliun G., Beretta S., Galimberti C. A., Cantisani T. A., Cecconi M., Celani M. G., Papetti R., Giorgi F. S., Aguglia U., Gasparini S., Ferlazzo E., Manganotti P., Crichiutti G., Bravar G., Giussani, G, Enia, G, Bianchi, E, Mecarelli, O, Beghi, E, Pulitano, P, Cagnetti, C, Baldinelli, S, La Neve, A, Tappata, M, Francavilla, T, De Maria, G, Sofia, V, Giuliano, L, Mainieri, G, Fatuzzo, D, Belcastro, V, Elia, M, D'Orsi, G, Lalla, A, Salmaggi, A, Brigo, F, Magaudda, A, Pisani, F, Galletta, S, Pisani, L, Raffaele, M, Cosenza, D, Villani, F, Quintas, R, Cervellione, R, Borroni, S, Meletti, S, Ferrarese, C, Barbella, G, Di Francesco, J, Bogliun, G, Beretta, S, Galimberti, C, Cantisani, T, Cecconi, M, Celani, M, Papetti, R, Giorgi, F, Aguglia, U, Gasparini, S, Ferlazzo, E, Manganotti, P, Crichiutti, G, Bravar, G, Giussani G., Enia G., Bianchi E., Mecarelli O., Beghi E., Pulitano P., Cagnetti C., Baldinelli S., La Neve A., Tappata M., Francavilla T., De Maria G., Sofia V., Giuliano L., Mainieri G., Fatuzzo D., Belcastro V., Elia M., D'Orsi G., Lalla A., Salmaggi A., Brigo F., Magaudda A., Pisani F., Galletta S., Pisani L. R., Raffaele M., Cosenza D., Villani F. S., Quintas R. M. M., Cervellione R., Borroni S., Meletti S., Ferrarese C., Barbella G., Di Francesco J., Bogliun G., Beretta S., Galimberti C. A., Cantisani T. A., Cecconi M., Celani M. G., Papetti R., Giorgi F. S., Aguglia U., Gasparini S., Ferlazzo E., Manganotti P., Crichiutti G., and Bravar G.
Abstract: Purpose: The purpose of this study was to assess the priorities of patients with epilepsy and caring physicians and the correspondence between these priorities. Methods: In this multicenter cross-sectional study, patients with epilepsy attending 21 Italian epilepsy centers and their caring physicians filled anonymously questionnaires on the needs and priorities in the management of the disease. Included were questions on patients' demographics, diagnosis, treatment, and outcome of epilepsy. The concordance between patients and their physicians was assessed on various aspects of the diagnosis and care of the disease. Patients' satisfaction with communication, services, and patient–doctor relationship was also assessed. Results: Included were 432 women and 355 men aged 15 to 88 years (median: 41 years). Disease duration ranged from 6 months to 75 years. A structural/metabolic etiology predominated (52.7%), followed by a (presumed) genetic etiology (33.0%). Seizure remission was present in 56.5% of cases. Comorbidities requiring chronic treatment were present in 27.5%, and comorbidities affecting self-sufficiency in 9.5%. Psychiatric comorbidity was present in 35.0%. Patients' priorities included discovery of the cause (89.1%), use of right drug (98.7%), use of a drug without chronic side effects (94.0%), and a life without restrictions (90.4%). Physicians' priorities included choice of right drug (83.5%) and use of drugs without chronic side effects (86.8%). Priorities varied with patients' age, sex, education, and occupation. Patient–doctor relationships were at least good in most cases. The information imparted was considered unsatisfactory by 21–44% of cases on seizure circumstances and complications, side effects of drugs, limitations of daily activities, and management of physiologic or pathologic conditions. Patients declared overall satisfaction, except for appointments (21.5%) and emergencies (30.8%). Conclusion: Patients and physicians' priorities in the mana
Published: 2020

16. Brain Aβ load association and sexual dimorphism of plasma BACE1 concentrations in cognitively normal individuals at risk for AD

Author: Vergallo, A., Houot, M., Cavedo, E., Lemercier, P., Vanmechelen, E., De Vos, A., Habert, M. -O., Potier, M. -C., Dubois, B., Lista, S., Hampel, H., Bakardjian, H., Benali, H., Bertin, H., Bonheur, J., Boukadida, L., Boukerrou, N., Chiesa, P., Colliot, O., Dubois, M., Epelbaum, S., Gagliardi, G., Genthon, R., Habert, M. O., Kas, A., Lamari, F., Levy, M., Metzinger, C., Mochel, F., Nyasse, F., Poisson, C., Potier, M. C., Revillon, M., Santos, A., Andrade, K. S., Sole, M., Surtee, M., Thiebaud de Schotten, M., Younsi, N., Afshar, M., Flores Aguilar, L., Akman-Anderson, L., Arenas, J., Avila, J., Babiloni, C., Baldacci, F., Batrla, R., Benda, N., Black, K. L., Bokde, A. L. W., Bonuccelli, U., Broich, K., Cacciola, F., Caraci, F., Castrillo, J., Ceravolo, R., Chiesa, P. A., Corvol, J. -C., Claudio Cuello, A., Cummings, J. L., Depypere, H., Duggento, A., Emanuele, E., Escott-Price, V., Federoff, H., Teresa Ferretti, M., Fiandaca, M., Frank, R. A., Garaci, F., Geerts, H., Giorgi, F. S., Goetzl, E. J., Graziani, M., Haberkamp, M., Marie-Odile, H., Herholz, K., Hernandez, F., Kapogiannis, D., Karran, E., Kiddle, S. J., Kim, S. H., Koronyo, Y., Koronyo-Hamaoui, M., Langevin, T., Lehericy, S., Lucia, A., Lorenceau, J., Mango, D., Mapstone, M., Neri, C., Nistico, R., O'Bryant, S. E., Palermo, G., Perry, G., Ritchie, C., Rossi, S., Saidi, A., Santarnecchi, E., Schneider, L. S., Sporns, O., Toschi, N., Verdooner, S. R., Villain, N., Welikovitch, L. A., Woodcock, J., Younesi, E., Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre d'investigation clinique Neurosciences [CHU Pitié Salpêtrière] (CIC Neurosciences), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Service de médecine nucléaire [CHU Pitié-Salpétrière]
Subjects: Male, 0301 basic medicine, Apolipoprotein E, Epidemiology, [SDV]Life Sciences [q-bio], PROGRESSION, Disease, Cognition, 0302 clinical medicine, Amyloid precursor protein, Medicine and Health Sciences, Aspartic Acid Endopeptidases, medicine.diagnostic_test, biology, Health Policy, Settore BIO/14, Brain, Alzheimer's disease, Healthy Volunteers, 3. Good health, GENOTYPE, ALZHEIMERS-DISEASE, Psychiatry and Mental health, Positron emission tomography, Cohort, Biomarker (medicine), Female, EXPRESSION, medicine.medical_specialty, BIOMARKERS, Standardized uptake value, 03 medical and health sciences, Cellular and Molecular Neuroscience, Sexual dimorphism, Apolipoproteins E, Sex Factors, Developmental Neuroscience, Alzheimer Disease, Internal medicine, mental disorders, medicine, Humans, BACE1 biomarkers, Aged, Plasma BACE1, DECLINE, Amyloid beta-Peptides, business.industry, 030104 developmental biology, Endocrinology, Positron-Emission Tomography, Disease modifying, biology.protein, Neurology (clinical), Amyloid Precursor Protein Secretases, Geriatrics and Gerontology, business, Biomarkers, 030217 neurology & neurosurgery
Abstract: Introduction: Successful development of effective beta-site amyloid precursor protein cleaving enzyme 1 (BACE1)-targeted therapies for early stages of Alzheimer's disease requires biomarker-guided intervention strategies. Methods: We investigated whether key biological factors such as sex, apolipoprotein E (APOE epsilon 4) allele, and age affect longitudinal plasma BACE1 concentrations in a large monocenter cohort of individuals at risk for Alzheimer's disease. We explored the relationship between plasma BACE1 concentrations and levels of brain amyloid-beta (A beta) deposition, using positron emission tomography global standard uptake value ratios. Results: Baseline and longitudinal mean concentrations of plasma BACE1 were significantly higher in women than men. We also found a positive significant impact of plasma BACE1 on baseline A beta-positron emission tomography global standard uptake value ratios. Discussion: Our results suggest a sexual dimorphism in BACE1-related upstream mechanisms of brain A beta production and deposition. We argue that plasma BACE1 should be considered in further biomarker validation and qualification studies as well as in BACE1 clinical trials. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.
Published: 2019

17. The management of epilepsy in clinical practice: Do the timing and severity of the disease influence the priorities of patients and the caring physicians? Data from the EPINEEDS study

Author: Enia, G., Giussani, G., Bianchi, E., Mecarelli, O., Beghi, E., Pulitano, P., Cagnetti, C., Baldinelli, S., Lattanzi, S., La Neve, A., Tappata, M., Francavilla, T., De Maria, G., Sofia, V., Giuliano, L., Mainieri, G., Fatuzzo, D., Belcastro, V., Elia, M., D'Orsi, G., Lalla, A., Salmaggi, A., Brigo, F., Magaudda, A., Pisani, F., Galletta, S., Pisani, L. R., Raffaele, M., Cosenza, D., Villani, F. S., Quintas, R. M. M., Cervellione, R., Borroni, S., Meletti, S., Ferrarese, C., Barbella, G., Di Francesco, J., Bogliun, G., Beretta, S., Galimberti, C. A., Cantisani, T. A., Cecconi, M., Celani, M. G., Papetti, R., Giorgi, F. S., Aguglia, U., Gasparini, S., Ferlazzo, E., Manganotti, P., Crichiutti, G., Bravar, G., Enia, G, Giussani, G, Bianchi, E, Mecarelli, O, Beghi, E, Pulitano, P, Cagnetti, C, Baldinelli, S, Lattanzi, S, La, N, Tappata, M, Francavilla, T, De Maria, G, Sofia, V, Giuliano, L, Mainieri, G, Fatuzzo, D, Belcastro, V, Elia, M, D'Orsi, G, Lalla, A, Salmaggi, A, Brigo, F, Magaudda, A, Pisani, F, Pisani, L, Raffaele, M, Cosenza, D, Villani, F, Quintas, R, Cervellione, R, Borroni, S, Meletti, S, Ferrarese, C, Barbella, G, Di Francesco, J, Bogliun, G, Beretta, S, Galimberti, C, Cantisani, T, Cecconi, M, Celani, M, Papetti, R, Giorgi, F, Aguglia, U, Gasparini, S, Ferlazzo, E, Manganotti, P, Crichiutti, G, and Bravar, G
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Concordance, Need, Disease, Epilepsy, Needs, Patients, Physicians, Priorities, Newly diagnosed epilepsy, Young Adult, 03 medical and health sciences, Behavioral Neuroscience, 0302 clinical medicine, Seizures, Anticonvulsant, medicine, Humans, 030212 general & internal medicine, Young adult, Aged, Aged, 80 and over, Patient, Prioritie, business.industry, Middle Aged, Caregiver, medicine.disease, Seizure, Clinical Practice, Caregivers, Italy, Neurology, Physician, Recurrent seizures, Family medicine, Population study, Anticonvulsants, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Human
Abstract: Objective The objective of this study was to assess the priorities of patients with epilepsy and their caring physicians with reference to the timing and severity of the disease. Methods This is a national survey in which patients with epilepsy followed in 21 Italian epilepsy centers, and their caring physicians were asked to fill anonymous questionnaires to collect data on different aspects of the disease and their needs and priorities in its management. The collected information included demographics, clinical profile and diagnosis, treatment and outcome of epilepsy. The questions were designed to understand the expectations of the patients and their caring physicians and verify the degree of concordance between patient and doctor. The study population was divided in six prognostic categories: (1) Newly diagnosed epilepsy; (2) Absence of seizures for at least 2 years; (3) Absence of seizures for at least 1 year or occasional seizures; (4) Nondrug-resistant recurrent seizures; (5) drug-resistant seizures; (6) surgical candidate. Results Of the 787 patients enrolled, 432 were women and 355 men aged 15 to 88 years (median 41 years). Disease duration ranged from 6 months to 75 years. The sample included 53 patients with newly diagnosed epilepsy, 283 without seizures for at least 2 years, 162 seizure-free for at least 1 year or with occasional seizures, 123 with nondrug-resistant recurrent seizures, 128 with drug-resistant seizures, and 38 surgical candidates. Significant differences were found between patients and physicians in terms of priorities and needs with reference to the management of the disease. While physicians tend to prioritize the information on the diagnosis and treatment of epilepsy depending on timing and severity, patients focus on the search of the cause, the side effects of drugs, and the effects of any new treatment on the control of seizures regardless of the prognostic category. In addition, physicians tend to undervalue the communication of specific information, like the risk of sudden unexpected death in epilepsy (SUDEP) or the existence of lay associations, which might be of special interest for selected categories of patients. Significance Differences between patients with epilepsy and their caring physicians in terms of needs and priorities and suboptimal communication call for the implementation of programs aimed at addressing the factors deemed most relevant by patients and caregivers for the management of the disease.
Published: 2021

18. Association Between CSF Beta-Amyloid and Apathy in Early-Stage Alzheimer Disease

Author: Vergallo, A., primary, Giampietri, L., additional, Pagni, C., additional, Giorgi, F. S., additional, Nicoletti, V., additional, Miccoli, M., additional, Libertini, P., additional, Petrozzi, L., additional, Bonuccelli, U., additional, and Tognoni, G., additional
Published: 2019
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19. Do antiepileptic drugs increase the risk of infectious diseases? A meta‐analysis of placebo‐controlled studies

Author: Zaccara, G., Giovannelli, F., Giorgi, F. S., Franco, V., Gasparini, S., and Tacconi, F. M.
Subjects: meta-analysis, adverse effects, antiepileptic drugs, infection, medDRA, Anticonvulsants, Communicable Diseases, Humans, Systematic Review and Meta–Analysis
Abstract: Experimental studies show that some antiepileptic drugs (AEDs) may modify natural immune defences, thus influencing the risk of developing infectious diseases. The aim of this meta-analysis was to explore whether AEDs as a class of drugs or singularly may increase risk of infectious diseases.A meta-analysis of all randomized, double-blind, placebo-controlled trials (RCTs) investigating any AED in any condition was performed. All terms that could be coded in the System Organ Classes (SOCs) of infections and infestations using the Medical Dictionary for Regulatory Activities were recorded. Additional subanalyses were performed also pooling together AEDs sharing similar mechanisms of action.Two hundreds and sixty-nine double-blind, placebo-controlled studies were identified and, among them, 127 RCTs with 16 AEDs (brivaracetam, gabapentin, lacosamide, levetiracetam, lamotrigine, oxcarbazepine, perampanel, pregabalin, phenytoin, remacemide, retigabine, rufinamide, tiagabine, topiramate, valproate, zonisamide) reported at least one of 19 symptoms or diseases that could be included in the Medical Dictionary for Regulatory Activities SOC term infections and infestations. These terms were singularly recorded and then pooled together in the SOC term infection and infestation. Topiramate was significantly associated with an increased risk of infection (risk difference = 0.04; 95% confidence interval = 0.01/0.06), while oxcarbazepine was significantly associated with a lower risk (-0.005; -0.09/-0.01). Risk difference of all studies with all AEDs showed a slight, but significantly increased risk of infection (0.01; 0.00/0.002). Levetiracetam and brivaracetam RCTs, when pooled together, were associated with a significantly increased risk of infection (0.03; 0.01/0.05).Some AEDs are associated with a mild increased risk of infection.
Published: 2017

20. Loud noise exposure produces DNA, neurotransmitter, and immunohistochemical alterations within specific brain areas

Author: Frenzilli, G., Ryskalin, Larisa, Ferrucci, Michela, Cantafora, E., Chelazzi, S., Giorgi, F. S., Lenzi, Paola, Frati, A., Scarcelli, V., Biagioni, F., Gambardella, S., Falleni, Alessandra, and Fornai, Francesco
Subjects: cell damage, cerebellum, hippocampus, striatum, rat, loud noise
Published: 2017

21. Randomized trial on the effects of a combined physical/cognitive training in aged MCI subjects: the Train the Brain study

Author: Maffei, L., Picano, E., Andreassi, M. G., Angelucci, A., Baldacci, F., Baroncelli, L., Begenisic, T., Bellinvia, P. F., Berardi, N., Biagi, L., Bonaccorsi, J., Bonanni, E., Bonuccelli, U., Borghini, A., Braschi, C., Broccardi, M., Bruno, R. M., Caleo, M., Carlesi, C., Carnicelli, L., Cartoni, G., Cecchetti, L., Cenni, M. C., Ceravolo, R., Chico, L., Cintoli, S., Cioni, G., Coscia, M., Costa, M., D’Angelo, G., D’Ascanio, P., Nes, M. De, Turco, S. Del, Coscio, E. Di, Galante, M. Di, Lascio, N. di, Faita, F., Falorni, I., Faraguna, U., Fenu, A., Fortunato, L., Franco, R., Gargani, L., Gargiulo, R., Ghiadoni, L., Giorgi, F. S., Iannarella, R., Iofrida, C., Kusmic, C., Limongi, F., Maestri, M., Maffei, M., Maggi, S., Mainardi, Marco, Mammana, L., Marabotti, A., Mariotti, V., Melissari, E., Mercuri, A., Micera, S., Molinaro, S., Narducci, R., Navarra, T., Noale, M., Pagni, C., Palumbo, S., Pasquariello, R., Pellegrini, S., Pietrini, P., Pizzorusso, T., Poli, A., Pratali, L., Retico, A., Ricciardi, E., Rota, G., Sale, A., Sbrana, S., Scabia, G., Scali, M., Scelfo, D., Sicari, R., Siciliano, G., Stea, F., Taddei, S., Tognoni, G., Tonacci, A., Tosetti, M., Turchi, S., Volpi, L., Mainardi, Marco (ORCID:0000-0003-2001-1287), Maffei, L., Picano, E., Andreassi, M. G., Angelucci, A., Baldacci, F., Baroncelli, L., Begenisic, T., Bellinvia, P. F., Berardi, N., Biagi, L., Bonaccorsi, J., Bonanni, E., Bonuccelli, U., Borghini, A., Braschi, C., Broccardi, M., Bruno, R. M., Caleo, M., Carlesi, C., Carnicelli, L., Cartoni, G., Cecchetti, L., Cenni, M. C., Ceravolo, R., Chico, L., Cintoli, S., Cioni, G., Coscia, M., Costa, M., D’Angelo, G., D’Ascanio, P., Nes, M. De, Turco, S. Del, Coscio, E. Di, Galante, M. Di, Lascio, N. di, Faita, F., Falorni, I., Faraguna, U., Fenu, A., Fortunato, L., Franco, R., Gargani, L., Gargiulo, R., Ghiadoni, L., Giorgi, F. S., Iannarella, R., Iofrida, C., Kusmic, C., Limongi, F., Maestri, M., Maffei, M., Maggi, S., Mainardi, Marco, Mammana, L., Marabotti, A., Mariotti, V., Melissari, E., Mercuri, A., Micera, S., Molinaro, S., Narducci, R., Navarra, T., Noale, M., Pagni, C., Palumbo, S., Pasquariello, R., Pellegrini, S., Pietrini, P., Pizzorusso, T., Poli, A., Pratali, L., Retico, A., Ricciardi, E., Rota, G., Sale, A., Sbrana, S., Scabia, G., Scali, M., Scelfo, D., Sicari, R., Siciliano, G., Stea, F., Taddei, S., Tognoni, G., Tonacci, A., Tosetti, M., Turchi, S., Volpi, L., and Mainardi, Marco (ORCID:0000-0003-2001-1287)
Abstract: Age-related cognitive impairment and dementia are an increasing societal burden. Epidemiological studies indicate that lifestyle factors, e.g. physical, cognitive and social activities, correlate with reduced dementia risk; moreover, positive effects on cognition of physical/cognitive training have been found in cognitively unimpaired elders. Less is known about effectiveness and action mechanisms of physical/cognitive training in elders already suffering from Mild Cognitive Impairment (MCI), a population at high risk for dementia. We assessed in 113 MCI subjects aged 65-89 years, the efficacy of combined physical-cognitive training on cognitive decline, Gray Matter (GM) volume loss and Cerebral Blood Flow (CBF) in hippocampus and parahippocampal areas, and on brain-blood-oxygenation-level-dependent (BOLD) activity elicited by a cognitive task, measured by ADAS-Cog scale, Magnetic Resonance Imaging (MRI), Arterial Spin Labeling (ASL) and fMRI, respectively, before and after 7 months of training vs. usual life. Cognitive status significantly decreased in MCI-no training and significantly increased in MCI-training subjects; training increased parahippocampal CBF, but no effect on GM volume loss was evident; BOLD activity increase, indicative of neural efficiency decline, was found only in MCI-no training subjects. These results show that a non pharmacological, multicomponent intervention improves cognitive status and indicators of brain health in MCI subjects.
Published: 2017

22. The role of sleep microstructure in the diagnostic yield ofEEG after sleep deprivation in temporal lobe epilepsy

Author: Carnicelli, Luca, Giorgi, F. S., Maestri, Michelangelo, Guida, Melania, Caciagli, L., Pizzanelli, C., Ferri, R., Bonuccelli, Ubaldo, and Bonanni, Enrica
Published: 2016

23. Non-rapid eye movement sleep instability in fronto-temporal dementia

Author: Maestri, Michelangelo, Carnicelli, Luca, Economou, N. T., Bonakis, A., Ktonas, P., Giorgi, F. S., DI COSCIO, Elisa, Tognoni, Gloria, Ventouras, E. C., Papageorgiou, S. G., Ferri, R., Bonuccelli, Ubaldo, and Bonanni, Enrica
Published: 2016

24. DNA integrity evaluation in an animal model of epilepsy

Author: Cantafora, E., Frenzilli*, G., Giorgi, F. S., Scarcelli, Vittoria, Nigro, Marco, and Fornai, Francesco
Published: 2014

25. Why we prefer levetiracetam over phenytoin for treatment of status epilepticus.

Author: Zaccara, G., Giorgi, F. S., Amantini, A., Giannasi, G., Campostrini, R., Giovannelli, F., Paganini, M., Nazerian, P., and the Tuscany study group on seizures in the emergency department and status epilepticus in adults
Subjects: *STATUS epilepticus treatment, *PHENYTOIN, *ANTICONVULSANTS, *INTRAVENOUS therapy, *DRUG resistance, *DRUG dosage, *THERAPEUTICS
Abstract: Over last fifty years, intravenous (iv) phenytoin (PHT) loading dose has been the treatment of choice for patients with benzodiazepine‐resistant convulsive status epilepticus and several guidelines recommended this treatment regimen with simultaneous iv diazepam. Clinical studies have never shown a better efficacy of PHT over other antiepileptic drugs. In addition, iv PHT loading dose is a complex and time‐consuming procedure which may expose patients to several risks, such as local cutaneous reactions (purple glove syndrome), severe hypotension and cardiac arrhythmias up to ventricular fibrillation and death, and increased risk of severe allergic reactions. A further disadvantage of PHT is that it is a strong enzymatic inducer and it may make ineffective several drugs that need to be used simultaneously with antiepileptic treatment. In patients with a benzodiazepine‐resistant status epilepticus, we suggest iv administration of levetiracetam as soon as possible. If levetiracetam would be ineffective, a further antiepileptic drug among those currently available for iv use (valproate, lacosamide, or phenytoin) can be added before starting third line treatment. [ABSTRACT FROM AUTHOR]
Published: 2018
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26. Disturbi cognitivi ed ecstasy: i modelli sperimentali confermano una marcata vulnerabilità del sistema libico

Author: Tamburini, I., Giorgi, F. S., Biagioni, F., Frenzilli, Giada, Nigro, Marco, Battaglia, G., Blandini, F., and Fornai, Francesco
Published: 2005

27. Previous Exposure to MDMA Produces Long-Lasting Alteration in Limbic Brain Excitability Measured by EEG Spectrum Analysis, Brain Metabolism and Seizure Susceptibility

Author: Giorgi, F. S., Pizzanelli, C., Ferrucci, Michela, Lazzeri, Gloria, Faetti, M., Giusiani, Mario, Pontarelli, F., Busceti, C. L., Murri, Luigi, and Fornai, Francesco
Published: 2005

28. L’inibizione transitoria o permanente della sintesi di noradrenalina peggiora la tossicità nigrostriatale in vari modelli di malattia di Parkinson

Author: Biagioni, F., Ferrucci, Michela, Busceti, C. L., Giorgi, F. S., Battaglia, G., Nicoletti, F., Ruggieri, S., and Fornai, Francesco
Published: 2005

29. La inibizione transitoria o permanente della sintesi di noradrenalina peggiora la tossicità nigrostriatale in vari modelli di malattia di Parkinson

Author: Biagioni, F., Ferrucci, Michela, Busceti, C. L., Giorgi, F. S., Battaglia, G., Nicoletti, F., Ruggieri, S., and Fornai, Francesco
Published: 2005

30. A short overview on the role of α-synuclein and proteasome in experimental models of Parkinson’s disease

Author: Giorgi, F. S., primary, Bandettini di Poggio, A., additional, Battaglia, G., additional, Pellegrini, A., additional, Murri, L., additional, Ruggieri, S., additional, Paparelli, A., additional, and Fornai, F., additional
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31. Natura dei fenomeni epilettici e modelli sperimentali di epilessia

Author: Fornai, Francesco, Giorgi, F. S., Ferrucci, Michela, Lazzeri, Gloria, and Paparelli, Antonio
Published: 2003

32. Cellular inclusions and cell death induced by amphetamines and proteasome inhibition: an 'in vitro' study

Author: Lazzeri, Gloria, Gesi, Marco, Giorgi, F. S., DE BLASI, A, Capobianco, L, Salvadorini, A, and Paparelli, Antonio
Published: 2003

33. Biochemical effects of the monoamine neurotoxins DSP-4 and MDMA in specific brain regions of MAO-B deficient mice

Author: Fornai, Francesco, Giorgi, F. S., Gesi, Marco, Chen, K, Alessandri, M. G., and Shih, J. C.
Subjects: dopamine, ecstasy, knockout, norepinephrine, serotonin
Published: 2001

34. Effects of Methamphetamine on the Cerebellar Cortex: A Preliminary Study

Author: FERRUCCI, M., primary, BUSCETI, C. L, additional, FALLENI, A., additional, GIORGI, F. S, additional, RUGGIERI, S., additional, and FORNAI, F., additional
Published: 2006
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35. Dopamine Stimulation via Infusion in the Lateral Ventricle

Author: BIAGIONI, F., primary, BUSCETI, C. L, additional, MOLINARO, G., additional, BATTAGLIA, G., additional, GIORGI, F. S, additional, RUGGIERI, S., additional, and FORNAI, F., additional
Published: 2006
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36. MDMA and Seizures: A Dangerous Liaison?

Author: GIORGI, F. S, primary, LAZZERI, G., additional, NATALE, G., additional, IUDICE, A., additional, RUGGIERI, S., additional, PAPARELLI, A., additional, MURRI, L., additional, and FORNAI, F., additional
Published: 2006
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37. Time-course and dose-response study on the effects of chronic l-DOPA administration on striatal dopamine levels and dopamine transporter following MPTP toxicity

Author: Fornai, F., Battaglia, G., Gesi, M., Giorgi, F. S., Orzi, F., Nicoletti, F., and Ruggieri, S.
Published: 2000
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38. Modulation of dihydroxyphenylacetaldehyde extracellular levels in vivo in the rat striatum after different kinds of pharmacological treatment

Author: Fornai, F., Giorgi, F. S., Bassi, L., Ferrucci, M., Alessandri, M. G., and Corsini, G. U.
Published: 2000
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39. The role of the locus coeruleus in the development of Parkinson's disease

Author: Gesi, M., Soldani, P., Giorgi, F. S., Santinami, A., Bonaccorsi, I., and Fornai, F.
Published: 2000
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40. Similar increases in extracellular lactic acid in the limbic system during epileptic and/or olfactory stimulation

Author: Fornai, F., Bassi, L., Gesi, M., Giorgi, F. S., Guerrini, R., Bonaccorsi, I., and Alessandri, M. G.
Published: 2000
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41. The placebo and nocebo responses in patients with epilepsy

Author: Fabio Giovannelli, Giorgi, F. S., and Zaccara, G.
Subjects: Meta-analysis, Epilepsy, Adverse effects, Nocebo, Antiepileptic drugs, Meta-regression, Placebo

42. The substantia nigra and seizures: Sex- and age-specific aspects, and the role of sex hormones

Author: Giorgi, F. S., Veliskova, J., Galanopoulou, A. S., Ravizza, T., and Solomon Moshe

43. ROLE OF A STANDARDIZED PARTIAL SLEEP-DEPRIVED EEG PROTOCOL IN THE DIAGNOSIS OF EPILEPSY, AND ITS CORRELATION TO CLINICAL AND NEUROIMAGING DATA

Author: Perini, D., Giorgi, F. S., Bonanni, E., Caserta, A., Emanuele Bartolini, Pizzanelli, C., Iudice, A., Pelliccia, V., and Murri, L.

44. The management of epilepsy in clinical practice: Do the needs manifested by the patients correspond to the priorities of the caring physicians? Findings from the EPINEEDS Study

Author: Giorgia Giussani, Gabriele Enia, Elisa Bianchi, Oriano Mecarelli, Ettore Beghi, Patrizia Pulitano, Claudia Cagnetti, Sara Baldinelli, Simona Lattanzi, Angela La Neve, Maria Tappatà, Teresa Francavilla, Giovanni De Maria, Vito Sofia, Loretta Giuliano, Greta Mainieri, Daniela Fatuzzo, Vincenzo Belcastro, Maurizio Elia, Giuseppe D'Orsi, Alessandra Lalla, Andrea Salmaggi, Francesco Brigo, Adriana Magaudda, Francesco Pisani, Santi Galletta, Laura R. Pisani, Massimo Raffaele, Domenico Cosenza, Flavio S. Villani, Rui M.M. Quintas, Rosa Cervellione, Simona Borroni, Stefano Meletti, Carlo Ferrarese, Giuseppina Barbella, Jacopo Di Francesco, Graziella Bogliun, Simone Beretta, Carlo A. Galimberti, Teresa A. Cantisani, Michela Cecconi, Maria G. Celani, Rossella Papetti, Filippo S. Giorgi, Umberto Aguglia, Sara Gasparini, Edoardo Ferlazzo, Paolo Manganotti, Giovanni Crichiutti, Giulia Bravar, Giussani, G., Enia, G., Bianchi, E., Mecarelli, O., Beghi, E., Pulitano, P., Cagnetti, C., Baldinelli, S., La Neve, A., Tappata, M., Francavilla, T., De Maria, G., Sofia, V., Giuliano, L., Mainieri, G., Fatuzzo, D., Belcastro, V., Elia, M., D'Orsi, G., Lalla, A., Salmaggi, A., Brigo, F., Magaudda, A., Pisani, F., Galletta, S., Pisani, L. R., Raffaele, M., Cosenza, D., Villani, F. S., Quintas, R. M. M., Cervellione, R., Borroni, S., Meletti, S., Ferrarese, C., Barbella, G., Di Francesco, J., Bogliun, G., Beretta, S., Galimberti, C. A., Cantisani, T. A., Cecconi, M., Celani, M. G., Papetti, R., Giorgi, F. S., Aguglia, U., Gasparini, S., Ferlazzo, E., Manganotti, P., Crichiutti, G., Bravar, G., Giussani, G, Enia, G, Bianchi, E, Mecarelli, O, Beghi, E, Pulitano, P, Cagnetti, C, Baldinelli, S, La Neve, A, Tappata, M, Francavilla, T, De Maria, G, Sofia, V, Giuliano, L, Mainieri, G, Fatuzzo, D, Belcastro, V, Elia, M, D'Orsi, G, Lalla, A, Salmaggi, A, Brigo, F, Magaudda, A, Pisani, F, Galletta, S, Pisani, L, Raffaele, M, Cosenza, D, Villani, F, Quintas, R, Cervellione, R, Borroni, S, Meletti, S, Ferrarese, C, Barbella, G, Di Francesco, J, Bogliun, G, Beretta, S, Galimberti, C, Cantisani, T, Cecconi, M, Celani, M, Papetti, R, Giorgi, F, Aguglia, U, Gasparini, S, Ferlazzo, E, Manganotti, P, Crichiutti, G, and Bravar, G
Subjects: Adult, Male, Pediatrics, medicine.medical_specialty, Activities of daily living, Adolescent, Patients, Concordance, Satisfaction, Need, Disease, 03 medical and health sciences, Behavioral Neuroscience, Psychiatric comorbidity, Epilepsy, Young Adult, 0302 clinical medicine, Genetic etiology, Seizures, Physicians, Surveys and Questionnaires, Medicine, Humans, Epilepsy Needs, 030212 general & internal medicine, Aged, Aged, 80 and over, Health Services Needs and Demand, Physician-Patient Relations, business.industry, Prioritie, Communication, Needs, Priorities, Disease Management, Middle Aged, medicine.disease, Clinical Practice, Cross-Sectional Studies, Neurology, Italy, Socioeconomic Factors, Etiology, Female, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Purpose The purpose of this study was to assess the priorities of patients with epilepsy and caring physicians and the correspondence between these priorities. Methods In this multicenter cross-sectional study, patients with epilepsy attending 21 Italian epilepsy centers and their caring physicians filled anonymously questionnaires on the needs and priorities in the management of the disease. Included were questions on patients' demographics, diagnosis, treatment, and outcome of epilepsy. The concordance between patients and their physicians was assessed on various aspects of the diagnosis and care of the disease. Patients' satisfaction with communication, services, and patient–doctor relationship was also assessed. Results Included were 432 women and 355 men aged 15 to 88 years (median: 41 years). Disease duration ranged from 6 months to 75 years. A structural/metabolic etiology predominated (52.7%), followed by a (presumed) genetic etiology (33.0%). Seizure remission was present in 56.5% of cases. Comorbidities requiring chronic treatment were present in 27.5%, and comorbidities affecting self-sufficiency in 9.5%. Psychiatric comorbidity was present in 35.0%. Patients' priorities included discovery of the cause (89.1%), use of right drug (98.7%), use of a drug without chronic side effects (94.0%), and a life without restrictions (90.4%). Physicians' priorities included choice of right drug (83.5%) and use of drugs without chronic side effects (86.8%). Priorities varied with patients' age, sex, education, and occupation. Patient–doctor relationships were at least good in most cases. The information imparted was considered unsatisfactory by 21–44% of cases on seizure circumstances and complications, side effects of drugs, limitations of daily activities, and management of physiologic or pathologic conditions. Patients declared overall satisfaction, except for appointments (21.5%) and emergencies (30.8%). Conclusion Patients and physicians' priorities in the management of epilepsy overlap only in part. Patients are satisfied with their caring physicians and less satisfied with communication and management of routine and emergency problems.
Published: 2020

45. Association of cerebrospinal fluid α-synuclein with total and phospho-tau181 protein concentrations and brain amyloid load in cognitively normal subjective memory complainers stratified by Alzheimer's disease biomarkers

Author: Vergallo, A, Bun, R, Toschi, N, Baldacci, F, Zetterberg, H, Blennow, K, Cavedo, E, Lamari, F, Habert, M, Dubois, B, Floris, R, Garaci, F, Lista, S, Hampel, H, Audrain, C, Auffret, A, Bakardjian, H, Batrancourt, B, Benakki, I, Benali, H, Bertin, H, Bertrand, A, Boukadida, L, Cacciamani, F, Causse, V, Cherif Touil, S, Chiesa, Pa, Colliot, O, Dalla Barba, G, Depaulis, M, Dos Santos, A, Dubois, M, Epelbaum, S, Fontaine, B, Francisque, H, Gagliardi, G, Genin, A, Genthon, R, Glasman, P, Gombert, F, Habert, Mo, Hewa, H, Houot, M, Jungalee, N, Kas, A, Kilani, M, La Corte, V, Le Roy, F, Lehericy, S, Letondor, C, Levy, M, Lowrey, M, Ly, J, Makiese, O, Masetti, I, Mendes, A, Metzinger, C, Michon, A, Mochel, F, Nait Arab, R, Nyasse, F, Perrin, C, Poirier, F, Poisson, C, Potier, Mc, Ratovohery, S, Revillon, M, Rojkova, K, Santos-Andrade, K, Schindler, R, Servera, Mc, Seux, L, Simon, V, Skovronsky, D, Thiebaut, M, Uspenskaya, O, Vlaincu, M, Aguilar, Lf, Babiloni, C, Benda, N, Black, Kl, Bokde, Alw, Bonuccelli, U, Broich, K, Bun, Rs, Cacciola, F, Castrillo, J, Ceravolo, R, Coman, Cm, Corvol, Jc, Cuello, Ac, Cummings, Jl, Depypere, H, Duggento, A, Durrleman, S, Escott-Price, V, Federoff, H, Ferretti, Mt, Fiandaca, M, Frank, Ra, George, N, Giorgi, Fs, Graziani, M, Haberkamp, M, Herholz, K, Karran, E, Kim, Sh, Koronyo, Y, Koronyo-Hamaoui, M, Langevin, T, Lehéricy, S, Lorenceau, J, Mapstone, M, Neri, C, Nisticò, R, Nyasse-Messene, F, O'Bryant, Se, Perry, G, Ritchie, C, Rossi, S, Santarnecchi, E, Schneider, Ls, Sporns, O, Verdooner, Sr, Villain, N, Welikovitch, L, Woodcock, J, Younesi, E, Vergallo, A., Bun, R. -S., Toschi, N., Baldacci, F., Zetterberg, H., Blennow, K., Cavedo, E., Lamari, F., Habert, M. -O., Dubois, B., Floris, R., Garaci, F., Lista, S., Hampel, H., Audrain, C., Auffret, A., Bakardjian, H., Batrancourt, B., Benakki, I., Benali, H., Bertin, H., Bertrand, A., Boukadida, L., Cacciamani, F., Causse, V., Cherif Touil, S., Chiesa, P. A., Colliot, O., Dalla Barba, G., Depaulis, M., Dos Santos, A., Dubois, M., Epelbaum, S., Fontaine, B., Francisque, H., Gagliardi, G., Genin, A., Genthon, R., Glasman, P., Gombert, F., Habert, M. O., Hewa, H., Houot, M., Jungalee, N., Kas, A., Kilani, M., La Corte, V., Le Roy, F., Lehericy, S., Letondor, C., Levy, M., Lowrey, M., Ly, J., Makiese, O., Masetti, I., Mendes, A., Metzinger, C., Michon, A., Mochel, F., Nait Arab, R., Nyasse, F., Perrin, C., Poirier, F., Poisson, C., Potier, M. C., Ratovohery, S., Revillon, M., Rojkova, K., Santos-Andrade, K., Schindler, R., Servera, M. C., Seux, L., Simon, V., Skovronsky, D., Thiebaut, M., Uspenskaya, O., Vlaincu, M., Aguilar, L. F., Babiloni, C., Benda, N., Black, K. L., Bokde, A. L. W., Bonuccelli, U., Broich, K., Bun, R. S., Cacciola, F., Castrillo, J., Ceravolo, R., Coman, C. M., Corvol, J. C., Cuello, A. C., Cummings, J. L., Depypere, H., Duggento, A., Durrleman, S., Escott-Price, V., Federoff, H., Ferretti, M. T., Fiandaca, M., Frank, R. A., George, N., Giorgi, F. S., Graziani, M., Haberkamp, M., Herholz, K., Karran, E., Kim, S. H., Koronyo, Y., Koronyo-Hamaoui, M., Langevin, T., Lorenceau, J., Mapstone, M., Neri, C., Nistico, R., Nyasse-Messene, F., O'Bryant, S. E., Perry, G., Ritchie, C., Rossi, S., Santarnecchi, E., Schneider, L. S., Sporns, O., Verdooner, S. R., Villain, N., Welikovitch, L., Woodcock, J., and Younesi, E.
Subjects: 0301 basic medicine, Epidemiology, Alzheimer's disease, Amyloid PET, Cerebrospinal fluid, Monocentric, Preclinical, Subjective memory complainers, SUVR, Synergistic, Tau protein, α-Synuclein, chemistry.chemical_compound, 0302 clinical medicine, biology, Health Policy, Settore FIS/07, Settore BIO/14, Pathophysiology, Psychiatry and Mental health, medicine.symptom, medicine.medical_specialty, Amyloid, Asymptomatic, 03 medical and health sciences, Cellular and Molecular Neuroscience, Developmental Neuroscience, Neurology (clinical), Geriatrics and Gerontology, Psychiatry and Mental Health, Internal medicine, mental disorders, medicine, Dementia, Alpha-synuclein, business.industry, Alzheimer's disease biomarkers, medicine.disease, 030104 developmental biology, Endocrinology, nervous system, chemistry, Subjective memory complainer, biology.protein, business, 030217 neurology & neurosurgery
Abstract: Introduction Several neurodegenerative brain proteinopathies, including Alzheimer's disease (AD), are associated with cerebral deposition of insoluble aggregates of α-synuclein. Previous studies reported a trend toward increased cerebrospinal fluid (CSF) α-synuclein (α-syn) concentrations in AD compared with other neurodegenerative diseases and healthy controls. Methods The pathophysiological role of CSF α-syn in asymptomatic subjects at risk of AD has not been explored. We performed a large-scale cross-sectional observational monocentric study of preclinical individuals at risk for AD (INSIGHT-preAD). Results We found a positive association between CSF α-syn concentrations and brain β-amyloid deposition measures as mean cortical standard uptake value ratios. We demonstrate positive correlations between CSF α-syn and both CSF t-tau and p-tau 181 concentrations. Discussion Animal models presented evidence, indicating that α-syn may synergistically and directly induce fibrillization of both tau and β-amyloid. Our data indicate an association of CSF α-syn with AD-related pathophysiological mechanisms, during the preclinical phase of the disease.
Published: 2018

46. Randomized trial on the effects of a combined physical/cognitive training in aged MCI subjects: The Train the Brain study

Author: Chiara Braschi, I. Falorni, Gennaro D'Angelo, Margherita Maffei, Antonella Mercuri, Marco Mainardi, Maria Chiara Scali, L. Gargani, Eugenio Picano, Francesco Stea, Nicoletta Berardi, G. Cartoni, Alessandro Tonacci, Roberto Ceravolo, Matteo Caleo, Claudia Kusmic, Silvestro Micera, M. Di Galante, Tommaso Pizzorusso, Michelangelo Maestri, Loredana Fortunato, Lamberto Maffei, Pietro Pietrini, Luca Cecchetti, L. Mammana, C. Carlesi, Maria Grazia Andreassi, Andrea Borghini, Silverio Sbrana, T. Navarra, Tatjana Begenisic, F. Limongi, Veronica Mariotti, Leda Volpi, F. S. Giorgi, Laura Biagi, Maria Cristina Cenni, Danilo Scelfo, Martina Coscia, Andrea Angelucci, Enrica Bonanni, Rosa Sicari, Ugo Faraguna, S. Del Turco, Lorenza Pratali, Roberta Franco, Marianna Noale, Joyce Bonaccorsi, Alessandro Sale, Sara Palumbo, Sabrina Molinaro, Gloria Tognoni, Rosa Maria Bruno, Rosa Pasquariello, Mario Costa, Laura Baroncelli, Cristina Pagni, S. Turchi, Erika Melissari, Filippo Baldacci, Roberta Narducci, M. Broccardi, M. De Nes, A. Marabotti, Giovanni Cioni, Stefano Taddei, E Di Coscio, Michela Tosetti, R. Iannarella, Simona Cintoli, R. Gargiulo, Francesco Faita, Gabriele Siciliano, Paola D'Ascanio, Giuseppina Rota, Silvia Pellegrini, P. F. Bellinvia, Ubaldo Bonuccelli, L. Carnicelli, A. Fenu, Andrea Poli, Emiliano Ricciardi, Caterina Iofrida, Stefania Maggi, Alessandra Retico, Gaia Scabia, Lorenzo Ghiadoni, N. Di Lascio, Lucia Chico, Maffei, L., Picano, E., Andreassi, M. G., Angelucci, A., Baldacci, Fabio, Baroncelli, L., Begenisic, Tatjana, Bellinvia, P. F., Berardi, N., Biagi, L., Bonaccorsi, Joyce, Bonanni, E., Bonuccelli, U., Borghini, Andrea, Braschi, Chiara, Broccardi, M., Bruno, R. M., Caleo, M., Carlesi, C., Carnicelli, L., Cartoni, G., Cecchetti, L., Cenni, MARIA CRISTINA, Ceravolo, R., Chico, L., Cintoli, S., Cioni, Giovanni, Coscia, M., Costa, M., D'Angelo, Giulia, D’Ascanio, P., Nes, M. De, Turco, S. Del, Coscio, E. Di, Galante, M. Di, Lascio, N. di, Faita, F., Falorni, I., Faraguna, U., Fenu, A., Fortunato, L., Franco, R., Gargani, L., Gargiulo, R., Ghiadoni, L., Giorgi, F. S., Iannarella, R., Iofrida, C., Kusmic, C., Limongi, F., Maestri, M., Maffei, M., Maggi, Stefania, Mainardi, M., Mammana, L., Marabotti, A., Mariotti, V., Melissari, E., Mercuri, A., Micera, Silvestro, Molinaro, S., Narducci, R., Navarra, T., Noale, M., Pagni, C., Palumbo, S., Pasquariello, R., Pellegrini, Silvia, Pietrini, Pietro, Pizzorusso, T., Poli, Andrea, Pratali, L., Retico, A., Ricciardi, E., Rota, G., Sale, A., Sbrana, S., Scabia, G., Scali, M., Scelfo, D., Sicari, R., Siciliano, G., Stea, F., Taddei, S., Tognoni, G., Tonacci, A., Tosetti, M., Turchi, S., and Volpi, LAURA MARINA
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Settore BIO/09 - FISIOLOGIA, education, ALzheimer's disease, Neuropsychological Tests, Settore BIO/09 - Fisiologia, behavioral disciplines and activities, Article, law.invention, 03 medical and health sciences, mild cognitive impairment, 0302 clinical medicine, Randomized controlled trial, law, mental disorders, neural plasticity, Alzheimer's disease, physical exercise, Humans, Medicine, Cognitive Dysfunction, physical exercise cognitive training social settind MCI RM fMRI, Psychiatry, Physical Therapy Modalities, Aged, Aged, 80 and over, Brain Mapping, Multidisciplinary, Cognitive Behavioral Therapy, business.industry, Brain, cognitive reserve, Magnetic Resonance Imaging, Cognitive training, Treatment Outcome, 030104 developmental biology, Physical therapy, environmental enrichment, Female, brain aging, business, 030217 neurology & neurosurgery
Abstract: Age-related cognitive impairment and dementia are an increasing societal burden. Epidemiological studies indicate that lifestyle factors, e.g. physical, cognitive and social activities, correlate with reduced dementia risk; moreover, positive effects on cognition of physical/cognitive training have been found in cognitively unimpaired elders. Less is known about effectiveness and action mechanisms of physical/cognitive training in elders already suffering from Mild Cognitive Impairment (MCI), a population at high risk for dementia. We assessed in 113 MCI subjects aged 65–89 years, the efficacy of combined physical-cognitive training on cognitive decline, Gray Matter (GM) volume loss and Cerebral Blood Flow (CBF) in hippocampus and parahippocampal areas, and on brain-blood-oxygenation-level-dependent (BOLD) activity elicited by a cognitive task, measured by ADAS-Cog scale, Magnetic Resonance Imaging (MRI), Arterial Spin Labeling (ASL) and fMRI, respectively, before and after 7 months of training vs. usual life. Cognitive status significantly decreased in MCI-no training and significantly increased in MCI-training subjects; training increased parahippocampal CBF, but no effect on GM volume loss was evident; BOLD activity increase, indicative of neural efficiency decline, was found only in MCI-no training subjects. These results show that a non pharmacological, multicomponent intervention improves cognitive status and indicators of brain health in MCI subjects.
Published: 2017

47. A hypothesis on prion disorders: are infectious, inherited, and sporadic causes so distinct?

Author: Fornai F, Ferrucci M, Gesi M, Bandettini di Poggio A, Giorgi FS, Biagioni F, and Paparelli A
Subjects: Brain metabolism, Brain pathology, Disease Transmission, Infectious, Inclusion Bodies genetics, Inclusion Bodies metabolism, Inclusion Bodies pathology, Models, Neurological, Prion Diseases genetics, Prion Diseases metabolism, Prions genetics, Proteasome Endopeptidase Complex genetics, Proteasome Endopeptidase Complex metabolism, Protein Folding, Protein Transport genetics, Ubiquitin genetics, Ubiquitin metabolism, Brain physiopathology, Prion Diseases physiopathology, Prions metabolism
Abstract: Prion diseases include a group of either sporadic, inherited or infectious disorders characterized by spongiform neurodegeneration and reactive glyosis in several brain regions. Whatever the origin, the neuropathological hallmark of prion diseases is the presence of brain aggregates containing an altered isoform of a cellular protein, named prion protein. Recent findings show the potential toxicity of the normal cellular prion protein, which occurs when its physiological metabolism is altered. In particular, several studies demonstrate that accumulation of the prion protein in the cytosol can be a consequence of an increased amount of misfolded prion proteins, a derangement of the correct protein trafficking or a reduced activity of the ubiquitin-proteasome system. The same effects can be a consequence of a mutation in the gene coding for the prion protein. In all these conditions, one assists to accumulation and self-replication of insoluble prion proteins which leads to a severe disease resembling what observed following typical "prion infections". This article provides an opinion aimed at reconciling the classic Prusiner's theory concerning the "prion concepts" with the present knowledge arising from experimental studies on neurodegenerative disorders, suggesting a few overlapping steps in the pathogenesis of these diseases.
Published: 2006
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48. Previous exposure to (+/-) 3,4-methylenedioxymethamphetamine produces long-lasting alteration in limbic brain excitability measured by electroencephalogram spectrum analysis, brain metabolism and seizure susceptibility.

Author: Giorgi FS, Pizzanelli C, Ferrucci M, Lazzeri G, Faetti M, Giusiani M, Pontarelli F, Busceti CL, Murri L, and Fornai F
Subjects: Animals, Biogenic Monoamines metabolism, Disease Susceptibility, Glucose metabolism, Male, Mice, Mice, Inbred C57BL, Seizures physiopathology, Brain metabolism, Electroencephalography, Kainic Acid, Limbic System drug effects, Limbic System physiology, N-Methyl-3,4-methylenedioxyamphetamine pharmacology, Seizures chemically induced
Abstract: Seizures represent the most common neurological emergency in ecstasy abusers; however, no study addressed whether (+/-) 3,4-methylenedioxymethamphetamine ("ecstasy") per se might produce long-lasting alterations in brain excitability related to a pro-convulsant effect. C57 Black mice were treated with three regimens of (+/-) 3,4-methylenedioxymethamphetamine (5mg/kg x 2 for 1, 2 or three consecutive days). Following the last dose of (+/-) 3,4-methylenedioxymethamphetamine, during a time interval of 8 weeks, the following procedures were carried out: 1) cortical electroencephalographic recordings, including power-spectrum analysis; 2) administration of sub-threshold doses of kainate; 3) measurement of regional [(14)C]2-deoxyglucose uptake; 4) monoamine assay. We demonstrate that all mice pre-treated with (+/-) 3,4-methylenedioxymethamphetamine showed long-lasting encephalographic changes with frequencies peaking at 3-4.5 Hz at the power-spectrum analysis. This is concomitant with latent brain hyperexcitability within selected limbic brain regions, as shown by seizure facilitation and long-lasting latent metabolic hyperactivity which can be unraveled by phasic glutamate stimulation. This study sheds new light into the brain targets of (+/-) 3,4-methylenedioxymethamphetamine and discloses the occurrence of (+/-) 3,4-methylenedioxymethamphetamine-induced latent hyperexcitability within limbic areas, while it might provide a model to study in controlled experimental conditions limbic seizures and status epilepticus in C57 Black mice. Persistent changes produced by (+/-) 3,4-methylenedioxymethamphetamine in limbic brain excitability might be responsible for seizures and limbic-related disorders in chronic (+/-) 3,4-methylenedioxymethamphetamine abusers.
Published: 2005
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49. Continuous subcutaneous infusion of apomorphine rescues nigro-striatal dopaminergic terminals following MPTP injection in mice.

Author: Battaglia G, Busceti CL, Cuomo L, Giorgi FS, Orzi F, De Blasi A, Nicoletti F, Ruggieri S, and Fornai F
Subjects: Animals, Corpus Striatum cytology, Corpus Striatum metabolism, Dopamine Agents pharmacology, Infusion Pumps statistics & numerical data, Injections, Subcutaneous, Mice, Mice, Inbred C57BL, Presynaptic Terminals metabolism, Substantia Nigra cytology, Substantia Nigra metabolism, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine pharmacology, Antiparkinson Agents pharmacology, Apomorphine pharmacology, Corpus Striatum drug effects, Dopamine metabolism, Presynaptic Terminals drug effects, Substantia Nigra drug effects
Abstract: Apomorphine has been introduced in the treatment of late-stage Parkinson's Disease (PD). The disadvantage of a short half-life of apomorphine is now overcome by the use of a continuous subcutaneous (s.c.) self-delivering system. We examined whether continuous s.c. infusion of apomorphine rescues nigro-striatal dopaminergic neurons from toxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. Apomorphine was continuously infused in mice by means of a s.c. minipump that delivered the drug at a rate of 0.5 or 3.15 mg/kg/day. MPTP induced a >80% reduction in striatal dopamine (DA) after one day. DA levels were still substantially reduced one month following MPTP injection, in spite of a partial recovery. Similarly, striatal immunoreactivity for tyrosine hydroxylase and dopamine transporter was markedly reduced at this time interval. Continuous s.c. infusion of apomorphine starting 40 h following MPTP injection rescued striatal dopaminergic terminals, as assessed by measurements of DA and its metabolites, as well as TH and DAT immunostaining after one month. The neurorescuing effect was more remarkable at a delivery rate of 3.15 mg/kg/day of apomorphine. In contrast, no rescue was observed when apomorphine was administered as a single daily s.c. bolus of 1 or 5mg/kg starting 40 h following MPTP. We conclude that apomorphine is able to rescue nigro-striatal dopaminergic neurons when continuously delivered at doses that are comparable to those delivered by minipumps in PD patients. These results suggest that continuous s.c. infusion of apomorphine not only relieves the symptoms, but also reduce the ongoing degeneration of nigro-striatal dopaminergic neurons in PD patients.
Published: 2002
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50. Biochemical effects of the monoamine neurotoxins DSP-4 and MDMA in specific brain regions of MAO-B-deficient mice.

Author: Fornai F, Giorgi FS, Gesi M, Chen K, Alessrì MG, and Shih JC
Subjects: Animals, Chromatography, High Pressure Liquid, Mice, Monoamine Oxidase genetics, Benzylamines toxicity, Biogenic Monoamines physiology, Brain Chemistry drug effects, Brain Chemistry genetics, Monoamine Oxidase deficiency, N-Methyl-3,4-methylenedioxyamphetamine toxicity, Neurotoxins toxicity
Abstract: Previous studies reported that drugs acting as monoamine oxidase (MAO)-B inhibitors prevented biochemical effects induced by the neurotoxins N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) and 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"). In this study, we administered DSP-4 (50 mg/kg) or MDMA (50 mg/kg x 2, 2 h apart) to MAO-B deficient mice. Monoamine content in various brain regions (cerebellum, frontal cortex, hippocampus, hypothalamus, striatum, substantia nigra) was assayed 1 week after neurotoxin administration. Injection of DSP-4 to wild-type mice caused a marked norepinephrine (NE) loss in specific brain regions. Unexpectedly, DSP-4 caused similar effects in MAO-B-deficient and in wild-type mice in all brain regions investigated. These results suggest that MAO-B is not involved in DSP-4 toxicity. In wild-types, the neurotoxin MDMA induced both serotonin (5HT) and dopamine (DA) depletion in specific brain areas. In MAO-B-deficient mice, 5HT depletion observed in wild-types did not occur. In contrast, MDMA produced a more pronounced DA loss in knockout mice compared with wild-types. The present findings, together with previous data obtained using selective enzyme inhibitors, suggest that MAO-B is not involved in the mechanism of action of DSP-4, whereas it plays opposite roles in MDMA-induced DA and 5HT depletions., (Copyright 2001 Wiley-Liss, Inc.)
Published: 2001
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