236 results on '"Innocenzo Rainero"'
Search Results
2. Acquired Pedophilia: international Delphi-method-based consensus guidelines
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Cristina Scarpazza, Cristiano Costa, Umberto Battaglia, Colleen Berryessa, Maria Lucia Bianchetti, Ilenia Caggiu, Orrin Devinsky, Stefano Ferracuti, Farah Focquaert, Arianna Forgione, Fredric Gilbert, Ambrogio Pennati, Pietro Pietrini, Innocenzo Rainero, Giuseppe Sartori, Russell Swerdlow, and Andrea S. Camperio Ciani
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Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Abstract Idiopathic and acquired pedophilia are two different disorders with two different etiologies. However, the differential diagnosis is still very difficult, as the behavioral indicators used to discriminate the two forms of pedophilia are underexplored, and clinicians are still devoid of clear guidelines describing the clinical and neuroscientific investigations suggested to help them with this difficult task. Furthermore, the consequences of misdiagnosis are not known, and a consensus regarding the legal consequences for the two kinds of offenders is still lacking. The present study used the Delphi method to reach a global consensus on the following six topics: behavioral indicators/red flags helpful for differential diagnosis; neurological conditions potentially leading to acquired pedophilia; neuroscientific investigations important for a correct understanding of the case; consequences of misdiagnosis; legal consequences; and issues and future perspectives. An international and multidisciplinary board of scientists and clinicians took part in the consensus statements as Delphi members. The Delphi panel comprised 52 raters with interdisciplinary competencies, including neurologists, psychiatrists, neuropsychologists, forensic psychologists, expert in ethics, etc. The final recommendations consisted of 63 statements covering the six different topics. The current study is the first expert consensus on a delicate topic such as pedophilia. Important exploitable consensual recommendations that can ultimately be of immediate use by clinicians to help with differential diagnosis and plan and guide therapeutic interventions are described, as well as future perspectives for researchers.
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- 2023
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3. Decreased resistin plasmatic concentrations in patients with Alzheimer's disease: A case-control study
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Andrea Marcinnò, Erica Gallo, Fausto Roveta, Silvia Boschi, Alberto Grassini, Innocenzo Rainero, and Elisa Rubino
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Adipokines ,Alzheimer's disease ,Frontotemporal dementia ,Adiponectin ,Leptin ,Resistin ,Science (General) ,Q1-390 ,Social sciences (General) ,H1-99 - Abstract
Previous studies suggested a role for adipokines in ageing and in several age-related diseases. The purpose of our study was to further elucidate adipokines involvement in neurodegeneration, investigating adiponectin, leptin and resistin in Alzheimer's disease (AD) and Frontotemporal Dementia (FTD). We enrolled for the study 70 subjects: 26 AD, 21 FTD, and 23 with other neurological (but not neurodegenerative) conditions (CTR, control group). According to a standardized protocol, we measured adipokines plasmatic levels, blood parameters of glucidic and lipidic metabolism, ESR, cerebrospinal fluid (CSF) markers of neurodegeneration (beta-amyloid, total-Tau, phosphorylated-Tau) and anthropometric parameters. In comparison with control group, we found lower resistin concentrations in patients with dementia, and in particular in AD (p < 0.001). In multivariate analysis, AD relative risk was reduced by resistin, when controlling for sex, age and anthropometric/metabolic parameters (RR = 0.71, P < 0.0001). Considering CSF biomarkers, we found a direct correlation between resistin and Aβ1-42 CSF concentration in patients (p < 0.001, r = 0.50). Lower resistin characterized AD patients in our study and AD, but not FTD, diagnosis risk was found to be inversely associated with resistin when controlling for confounders. We hypothesize that resistin-linked metabolic profile has to be reconsidered and further investigated in AD.
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- 2022
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4. Author Correction: Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
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Itziar de Rojas, Sonia Moreno-Grau, Niccolo Tesi, Benjamin Grenier-Boley, Victor Andrade, Iris E. Jansen, Nancy L. Pedersen, Najada Stringa, Anna Zettergren, Isabel Hernández, Laura Montrreal, Carmen Antúnez, Anna Antonell, Rick M. Tankard, Joshua C. Bis, Rebecca Sims, Céline Bellenguez, Inés Quintela, Antonio González-Perez, Miguel Calero, Emilio Franco-Macías, Juan Macías, Rafael Blesa, Laura Cervera-Carles, Manuel Menéndez-González, Ana Frank-García, Jose Luís Royo, Fermin Moreno, Raquel Huerto Vilas, Miquel Baquero, Mónica Diez-Fairen, Carmen Lage, Sebastián García-Madrona, Pablo García-González, Emilio Alarcón-Martín, Sergi Valero, Oscar Sotolongo-Grau, Abbe Ullgren, Adam C. Naj, Afina W. Lemstra, Alba Benaque, Alba Pérez-Cordón, Alberto Benussi, Alberto Rábano, Alessandro Padovani, Alessio Squassina, Alexandre de Mendonça, Alfonso Arias Pastor, Almar A. L. Kok, Alun Meggy, Ana Belén Pastor, Ana Espinosa, Anaïs Corma-Gómez, Angel Martín Montes, Ángela Sanabria, Anita L. DeStefano, Anja Schneider, Annakaisa Haapasalo, Anne Kinhult Ståhlbom, Anne Tybjærg-Hansen, Annette M. Hartmann, Annika Spottke, Arturo Corbatón-Anchuelo, Arvid Rongve, Barbara Borroni, Beatrice Arosio, Benedetta Nacmias, Børge G. Nordestgaard, Brian W. Kunkle, Camille Charbonnier, Carla Abdelnour, Carlo Masullo, Carmen Martínez Rodríguez, Carmen Muñoz-Fernandez, Carole Dufouil, Caroline Graff, Catarina B. Ferreira, Caterina Chillotti, Chandra A. Reynolds, Chiara Fenoglio, Christine Van Broeckhoven, Christopher Clark, Claudia Pisanu, Claudia L. Satizabal, Clive Holmes, Dolores Buiza-Rueda, Dag Aarsland, Dan Rujescu, Daniel Alcolea, Daniela Galimberti, David Wallon, Davide Seripa, Edna Grünblatt, Efthimios Dardiotis, Emrah Düzel, Elio Scarpini, Elisa Conti, Elisa Rubino, Ellen Gelpi, Eloy Rodriguez-Rodriguez, Emmanuelle Duron, Eric Boerwinkle, Evelyn Ferri, Fabrizio Tagliavini, Fahri Küçükali, Florence Pasquier, Florentino Sanchez-Garcia, Francesca Mangialasche, Frank Jessen, Gaël Nicolas, Geir Selbæk, Gemma Ortega, Geneviève Chêne, Georgios Hadjigeorgiou, Giacomina Rossi, Gianfranco Spalletta, Giorgio Giaccone, Giulia Grande, Giuliano Binetti, Goran Papenberg, Harald Hampel, Henri Bailly, Henrik Zetterberg, Hilkka Soininen, Ida K. Karlsson, Ignacio Alvarez, Ildebrando Appollonio, Ina Giegling, Ingmar Skoog, Ingvild Saltvedt, Innocenzo Rainero, Irene Rosas Allende, Jakub Hort, Janine Diehl-Schmid, Jasper Van Dongen, Jean-Sebastien Vidal, Jenni Lehtisalo, Jens Wiltfang, Jesper Qvist Thomassen, Johannes Kornhuber, Jonathan L. Haines, Jonathan Vogelgsang, Juan A. Pineda, Juan Fortea, Julius Popp, Jürgen Deckert, Katharina Buerger, Kevin Morgan, Klaus Fließbach, Kristel Sleegers, Laura Molina-Porcel, Lena Kilander, Leonie Weinhold, Lindsay A. Farrer, Li-San Wang, Luca Kleineidam, Lucia Farotti, Lucilla Parnetti, Lucio Tremolizzo, Lucrezia Hausner, Luisa Benussi, Lutz Froelich, M. Arfan Ikram, M. Candida Deniz-Naranjo, Magda Tsolaki, Maitée Rosende-Roca, Malin Löwenmark, Marc Hulsman, Marco Spallazzi, Margaret A. Pericak-Vance, Margaret Esiri, María Bernal Sánchez-Arjona, Maria Carolina Dalmasso, María Teresa Martínez-Larrad, Marina Arcaro, Markus M. Nöthen, Marta Fernández-Fuertes, Martin Dichgans, Martin Ingelsson, Martin J. Herrmann, Martin Scherer, Martin Vyhnalek, Mary H. Kosmidis, Mary Yannakoulia, Matthias Schmid, Michael Ewers, Michael T. Heneka, Michael Wagner, Michela Scamosci, Miia Kivipelto, Mikko Hiltunen, Miren Zulaica, Montserrat Alegret, Myriam Fornage, Natalia Roberto, Natasja M. van Schoor, Nazib M. Seidu, Nerisa Banaj, Nicola J. Armstrong, Nikolaos Scarmeas, Norbert Scherbaum, Oliver Goldhardt, Oliver Hanon, Oliver Peters, Olivia Anna Skrobot, Olivier Quenez, Ondrej Lerch, Paola Bossù, Paolo Caffarra, Paolo Dionigi Rossi, Paraskevi Sakka, Patrizia Mecocci, Per Hoffmann, Peter A. Holmans, Peter Fischer, Peter Riederer, Qiong Yang, Rachel Marshall, Rajesh N. Kalaria, Richard Mayeux, Rik Vandenberghe, Roberta Cecchetti, Roberta Ghidoni, Ruth Frikke-Schmidt, Sandro Sorbi, Sara Hägg, Sebastiaan Engelborghs, Seppo Helisalmi, Sigrid Botne Sando, Silke Kern, Silvana Archetti, Silvia Boschi, Silvia Fostinelli, Silvia Gil, Silvia Mendoza, Simon Mead, Simona Ciccone, Srdjan Djurovic, Stefanie Heilmann-Heimbach, Steffi Riedel-Heller, Teemu Kuulasmaa, Teodoro del Ser, Thibaud Lebouvier, Thomas Polak, Tiia Ngandu, Timo Grimmer, Valentina Bessi, Valentina Escott-Price, Vilmantas Giedraitis, Vincent Deramecourt, Wolfgang Maier, Xueqiu Jian, Yolande A. L. Pijnenburg, EADB contributors, DEGESCO consortium, IGAP (ADGC, CHARGE, EADI, GERAD), PGC-ALZ consortia, Patrick Gavin Kehoe, Guillermo Garcia-Ribas, Pascual Sánchez-Juan, Pau Pastor, Jordi Pérez-Tur, Gerard Piñol-Ripoll, Adolfo Lopez de Munain, Jose María García-Alberca, María J. Bullido, Victoria Álvarez, Alberto Lleó, Luis M. Real, Pablo Mir, Miguel Medina, Philip Scheltens, Henne Holstege, Marta Marquié, María Eugenia Sáez, Ángel Carracedo, Philippe Amouyel, Gerard D. Schellenberg, Julie Williams, Sudha Seshadri, Cornelia M. van Duijn, Karen A. Mather, Raquel Sánchez-Valle, Manuel Serrano-Ríos, Adelina Orellana, Lluís Tárraga, Kaj Blennow, Martijn Huisman, Ole A. Andreassen, Danielle Posthuma, Jordi Clarimón, Mercè Boada, Wiesje M. van der Flier, Alfredo Ramirez, Jean-Charles Lambert, Sven J. van der Lee, and Agustín Ruiz
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Science - Published
- 2023
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5. Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
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Itziar de Rojas, Sonia Moreno-Grau, Niccolo Tesi, Benjamin Grenier-Boley, Victor Andrade, Iris E. Jansen, Nancy L. Pedersen, Najada Stringa, Anna Zettergren, Isabel Hernández, Laura Montrreal, Carmen Antúnez, Anna Antonell, Rick M. Tankard, Joshua C. Bis, Rebecca Sims, Céline Bellenguez, Inés Quintela, Antonio González-Perez, Miguel Calero, Emilio Franco-Macías, Juan Macías, Rafael Blesa, Laura Cervera-Carles, Manuel Menéndez-González, Ana Frank-García, Jose Luís Royo, Fermin Moreno, Raquel Huerto Vilas, Miquel Baquero, Mónica Diez-Fairen, Carmen Lage, Sebastián García-Madrona, Pablo García-González, Emilio Alarcón-Martín, Sergi Valero, Oscar Sotolongo-Grau, Abbe Ullgren, Adam C. Naj, Afina W. Lemstra, Alba Benaque, Alba Pérez-Cordón, Alberto Benussi, Alberto Rábano, Alessandro Padovani, Alessio Squassina, Alexandre de Mendonça, Alfonso Arias Pastor, Almar A. L. Kok, Alun Meggy, Ana Belén Pastor, Ana Espinosa, Anaïs Corma-Gómez, Angel Martín Montes, Ángela Sanabria, Anita L. DeStefano, Anja Schneider, Annakaisa Haapasalo, Anne Kinhult Ståhlbom, Anne Tybjærg-Hansen, Annette M. Hartmann, Annika Spottke, Arturo Corbatón-Anchuelo, Arvid Rongve, Barbara Borroni, Beatrice Arosio, Benedetta Nacmias, Børge G. Nordestgaard, Brian W. Kunkle, Camille Charbonnier, Carla Abdelnour, Carlo Masullo, Carmen Martínez Rodríguez, Carmen Muñoz-Fernandez, Carole Dufouil, Caroline Graff, Catarina B. Ferreira, Caterina Chillotti, Chandra A. Reynolds, Chiara Fenoglio, Christine Van Broeckhoven, Christopher Clark, Claudia Pisanu, Claudia L. Satizabal, Clive Holmes, Dolores Buiza-Rueda, Dag Aarsland, Dan Rujescu, Daniel Alcolea, Daniela Galimberti, David Wallon, Davide Seripa, Edna Grünblatt, Efthimios Dardiotis, Emrah Düzel, Elio Scarpini, Elisa Conti, Elisa Rubino, Ellen Gelpi, Eloy Rodriguez-Rodriguez, Emmanuelle Duron, Eric Boerwinkle, Evelyn Ferri, Fabrizio Tagliavini, Fahri Küçükali, Florence Pasquier, Florentino Sanchez-Garcia, Francesca Mangialasche, Frank Jessen, Gaël Nicolas, Geir Selbæk, Gemma Ortega, Geneviève Chêne, Georgios Hadjigeorgiou, Giacomina Rossi, Gianfranco Spalletta, Giorgio Giaccone, Giulia Grande, Giuliano Binetti, Goran Papenberg, Harald Hampel, Henri Bailly, Henrik Zetterberg, Hilkka Soininen, Ida K. Karlsson, Ignacio Alvarez, Ildebrando Appollonio, Ina Giegling, Ingmar Skoog, Ingvild Saltvedt, Innocenzo Rainero, Irene Rosas Allende, Jakub Hort, Janine Diehl-Schmid, Jasper Van Dongen, Jean-Sebastien Vidal, Jenni Lehtisalo, Jens Wiltfang, Jesper Qvist Thomassen, Johannes Kornhuber, Jonathan L. Haines, Jonathan Vogelgsang, Juan A. Pineda, Juan Fortea, Julius Popp, Jürgen Deckert, Katharina Buerger, Kevin Morgan, Klaus Fließbach, Kristel Sleegers, Laura Molina-Porcel, Lena Kilander, Leonie Weinhold, Lindsay A. Farrer, Li-San Wang, Luca Kleineidam, Lucia Farotti, Lucilla Parnetti, Lucio Tremolizzo, Lucrezia Hausner, Luisa Benussi, Lutz Froelich, M. Arfan Ikram, M. Candida Deniz-Naranjo, Magda Tsolaki, Maitée Rosende-Roca, Malin Löwenmark, Marc Hulsman, Marco Spallazzi, Margaret A. Pericak-Vance, Margaret Esiri, María Bernal Sánchez-Arjona, Maria Carolina Dalmasso, María Teresa Martínez-Larrad, Marina Arcaro, Markus M. Nöthen, Marta Fernández-Fuertes, Martin Dichgans, Martin Ingelsson, Martin J. Herrmann, Martin Scherer, Martin Vyhnalek, Mary H. Kosmidis, Mary Yannakoulia, Matthias Schmid, Michael Ewers, Michael T. Heneka, Michael Wagner, Michela Scamosci, Miia Kivipelto, Mikko Hiltunen, Miren Zulaica, Montserrat Alegret, Myriam Fornage, Natalia Roberto, Natasja M. van Schoor, Nazib M. Seidu, Nerisa Banaj, Nicola J. Armstrong, Nikolaos Scarmeas, Norbert Scherbaum, Oliver Goldhardt, Oliver Hanon, Oliver Peters, Olivia Anna Skrobot, Olivier Quenez, Ondrej Lerch, Paola Bossù, Paolo Caffarra, Paolo Dionigi Rossi, Paraskevi Sakka, Per Hoffmann, Peter A. Holmans, Peter Fischer, Peter Riederer, Qiong Yang, Rachel Marshall, Rajesh N. Kalaria, Richard Mayeux, Rik Vandenberghe, Roberta Cecchetti, Roberta Ghidoni, Ruth Frikke-Schmidt, Sandro Sorbi, Sara Hägg, Sebastiaan Engelborghs, Seppo Helisalmi, Sigrid Botne Sando, Silke Kern, Silvana Archetti, Silvia Boschi, Silvia Fostinelli, Silvia Gil, Silvia Mendoza, Simon Mead, Simona Ciccone, Srdjan Djurovic, Stefanie Heilmann-Heimbach, Steffi Riedel-Heller, Teemu Kuulasmaa, Teodoro del Ser, Thibaud Lebouvier, Thomas Polak, Tiia Ngandu, Timo Grimmer, Valentina Bessi, Valentina Escott-Price, Vilmantas Giedraitis, Vincent Deramecourt, Wolfgang Maier, Xueqiu Jian, Yolande A. L. Pijnenburg, EADB contributors, DEGESCO consortium, IGAP (ADGC, CHARGE, EADI, GERAD), PGC-ALZ consortia, Patrick Gavin Kehoe, Guillermo Garcia-Ribas, Pascual Sánchez-Juan, Pau Pastor, Jordi Pérez-Tur, Gerard Piñol-Ripoll, Adolfo Lopez de Munain, Jose María García-Alberca, María J. Bullido, Victoria Álvarez, Alberto Lleó, Luis M. Real, Pablo Mir, Miguel Medina, Philip Scheltens, Henne Holstege, Marta Marquié, María Eugenia Sáez, Ángel Carracedo, Philippe Amouyel, Gerard D. Schellenberg, Julie Williams, Sudha Seshadri, Cornelia M. van Duijn, Karen A. Mather, Raquel Sánchez-Valle, Manuel Serrano-Ríos, Adelina Orellana, Lluís Tárraga, Kaj Blennow, Martijn Huisman, Ole A. Andreassen, Danielle Posthuma, Jordi Clarimón, Mercè Boada, Wiesje M. van der Flier, Alfredo Ramirez, Jean-Charles Lambert, Sven J. van der Lee, and Agustín Ruiz
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Science - Abstract
Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.
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- 2021
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6. Depression, Anxiety and Sleep Alterations in Caregivers of Persons With Dementia After 1-Year of COVID-19 Pandemic
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Cinzia Bussè, Teresa Barnini, Milena Zucca, Innocenzo Rainero, Stefano Mozzetta, Andrea Zangrossi, and Annachiara Cagnin
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dementia ,COVID ,lockdown ,burden ,caregivers ,depression ,Psychiatry ,RC435-571 - Abstract
BackgroundSocial isolation due to COVID-19 pandemic has an important psychological impact particularly in persons with dementia and their informal caregivers.AimTo assess frequency and severity of long-term stress-related symptoms in caregivers of patients with dementia 1-year after the beginning of COVID-19 pandemic and to identify predictors of psychological outcomes.MethodsEighty-five caregivers were involved in a longitudinal study with 1-year follow-up during pandemic in Italy. At baseline in April 2020 a telephone interview assessed socio-demographic characteristics of caregivers and self-perception of distress symptoms. After 1 year, between March and April 2021, the same standardized interview was delivered to the caregivers' sample. In addition, scales assessing levels of depression and anxiety (DASS-21), sleep disturbances (PSQI) and coping strategies (COPE-NVI) were administered to the caregivers and to 50 age and sex-matched non-caregivers subjects. Linear regression analysis was performed to investigate the power of baseline variables to predict long-term psychological outcomes.ResultsAfter 1 year of pandemic frequency of caregivers' stress-related symptoms increased respect to baseline: depression (60 vs. 5, 9%; p < 0.001), anxiety (45, 9 vs. 29, 4%; p = 0.035), irritability (49, 4 vs. 24, 7%; p < 0.001), and anguish (31, 7 vs. 10, 6%; p < 0.001). Frequency of severe depression was higher in caregivers than in non-caregivers (p = 0.002) although mean levels of depression were comparable in the two groups. Long-term higher depression was predicted by a model built on baseline information (r2 = 0.53, p < 0.001) where being female (t = −3.61, p < 0.001), having lower education (t = −2.15, p = 0.04), presence of feelings of overwhelm (t = 2.29, p = 0.02) and isolation (t = 2.12, p = 0.04) were significant predictors. Female sex was also predictive of anxiety (t = −2.7, p = 0.01) and poor sleep quality (t = −2.17, p = 0.03).DiscussionAt 1 year follow-up caregivers of patients with dementia reported higher prevalence of all stress-related symptoms respect to the acute phase of lockdown, particularly depression. Long-lasting stressful conditions may cause exhaustion of resilience factors and increased depression. Planning interventions should support caregivers to enable them to continue with their role during pandemic.
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- 2022
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7. Analysis of the DNA methylation pattern of the promoter region of calcitonin gene-related peptide 1 gene in patients with episodic migraine: An exploratory case-control study
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Elisa Rubino, Silvia Boschi, Elisa Giorgio, Elisa Pozzi, Andrea Marcinnò, Erica Gallo, Fausto Roveta, Alberto Grassini, Alfredo Brusco, and Innocenzo Rainero
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Migraine ,CALCA gene ,CGRP ,Epigenetics ,Methylation ,CpG islands ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Recent studies suggested that epigenetic mechanisms, including DNA methylation, may be involved in migraine pathogenesis. The calcitonin gene-related peptide (CGRP), encoded by calcitonin gene-related peptide 1 (CALCA) gene, plays a key role in the disease. The aim of the study was to evaluate DNA methylation of CALCA gene in patients with episodic migraine. 22 patients with episodic migraine (F/M 15/7, mean age 39.7 ± 13.4 years) and 20 controls (F/M 12/8, mean age 40.5 ± 14.8 years) were recruited. Genomic DNA was extracted from peripheral blood. Cytosine-to-thymine conversion was obtained with sodium bisulfite. The methylation pattern of two CpG islands in the promoter region of CALCA gene was analyzed. No difference of methylation of the 30 CpG sites at the distal region of CALCA promoter was observed between migraineurs and controls. Interestingly, in patients with episodic migraine the methylation level was lower in 2 CpG sites at the proximal promoter region (CpG −1461, p = 0.037, and −1415, p = 0.035, respectively). Furthermore, DNA methylation level at different CpG sites correlates with several clinical characteristics of the disease, as age at onset, presence of nausea/vomiting, depression and anxiety (p
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- 2022
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8. Aβ42 as a Biomarker of Alzheimer’s Disease: Is Saliva a Viable Alternative to Cerebrospinal Fluid?
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Silvia Boschi, Fausto Roveta, Alberto Grassini, Andrea Marcinnò, Aurora Cermelli, Fabio Ferrandes, Innocenzo Rainero, and Elisa Rubino
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saliva ,CSF ,beta amyloid 42 ,Alzheimer’s disease ,biomarkers ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
The identification of reliable biomarkers in biological fluids is paramount to optimizing the diagnosis of Alzheimer’s disease (AD). Measurement of Aβ42, t-tau, and p-tau in cerebrospinal fluid (CSF) is the most accepted method to support the diagnosis of AD. However, lumbar puncture represents an invasive investigation, whereas saliva is one of the most accessible body fluids. The aim of our study was to investigate salivary concentrations in AD and evaluate the correlation between salivary and CSF Aβ42 concentrations in AD patients, patients with non-AD dementias, and controls. We recruited 100 subjects: 18 AD patients, 64 patients with non-AD dementias, and 18 controls. The mean saliva Aβ42 concentrations in AD patients were higher than in controls (p < 0.001), and to patients with non-AD dementias (p = 0.001). A significant negative correlation between salivary and CSF Aβ42 concentrations was found in the overall group (r = −0.562, p < 0.001) and in non-AD patients (r = −0.443, p < 0.001). Salivary Aβ42 concentrations positively correlated with CSF t-tau (r = 0.321, p = 0.001) and p-tau (r = 0.297, p = 0.001). Our study showed that in AD patients’ saliva, Aβ42 concentrations are specifically increased, and we found an interesting negative correlation between CSF and salivary Aβ42 concentrations that warrants further investigation.
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- 2022
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9. Polymorphisms of the Proinflammatory Cytokine Genes Modulate the Response to NSAIDs but Not to Triptans in Migraine Attacks
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Elisa Rubino, Andrea Marcinnò, Alberto Grassini, Elisa Maria Piella, Fabio Ferrandes, Fausto Roveta, Silvia Boschi, Aurora Cermelli, Salvatore Gallone, Lidia Savi, and Innocenzo Rainero
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migraine ,polymorphism ,cytokines ,TNF-α ,NSAIDs ,triptans ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Migraine is a common neurovascular disorder characterized by recurrent episodes of headache and associated neurological symptoms. At present, a significant portion of patients do not obtain a satisfactory response to acute pain-relieving therapies, including NSAIDs and triptans. In this context, pharmacogenetics plays a key role in the understanding of such a diverse response. In order to investigate whether functional polymorphisms in proinflammatory cytokine genes (IL-1α, IL-1β, IL-1RN; IL-6 and TNF-α) may influence the response to acute treatment, 313 consecutive patients with episodic migraine without aura were enrolled. Pain relief by administration of NSAIDs or triptans for three consecutive migraine attacks was evaluated. We found a significant association between A allele of the TNF-α promoter (−308 A/G) and a lack of efficacy after NSAID administration (p < 0.01, OR 2.51, 95% CI: 1.33 < OR < 4.75 compared to the G allele). Remaining polymorphisms had no significant effect on pain relief. Our study showed that a functional polymorphism in the TNF-α gene significantly modulates the clinical response to NSAID administration in acute attacks. Patients with higher production of the active cytokine during stress showed a significantly lower anti-migraine effect. Our results further support a role for TNF-α in the pathophysiological mechanisms of migraine attack.
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- 2022
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10. Investigating p62 Concentrations in Cerebrospinal Fluid of Patients with Dementia: A Potential Autophagy Biomarker In Vivo?
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Elisa Rubino, Silvia Boschi, Fausto Roveta, Andrea Marcinnò, Aurora Cermelli, Cristina Borghese, Maria Claudia Vigliani, and Innocenzo Rainero
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SQSTM1/p62 ,biomarkers ,autophagy ,cerebrospinal fluid ,Alzheimer’s disease ,frontotemporal dementia ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Several studies have revealed defects in autophagy in neurodegenerative disorders including Alzheimer’s disease (AD) and frontotemporal dementia (FTD). SQSTM1/p62 plays a key role in the autophagic machinery and may serve as a marker for autophagic flux in vivo. We investigated the role of p62 in neurodegeneration, analyzing its concentrations in the CSF of AD and FTD patients. We recruited 76 participants: 22 patients with AD, 28 patients with FTD, and 26 controls. CSF p62 concentrations were significantly increased in AD and FTD patients when compared to controls, which persisted after adjusting for age (p = 0.01 and p = 0.008, respectively). In female FTD patients, p62 positively correlated with the neurodegenerative biomarkers t-Tau and p-Tau. A significant correlation between CSF p62 concentrations and several clinical features of AD was found. Our data show that p62 is increased in CSF of AD and FTD patients, suggesting a key role of autophagy in these two disorders. The levels of p62 in CSF may reflect an altered autophagic flux, and p62 could represent a potential biomarker of neurodegeneration.
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- 2022
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11. Investigating Neuroimaging Correlates of Early Frailty in Patients With Behavioral Variant Frontotemporal Dementia: A MRI and FDG-PET Study
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Martina Amanzio, Sara Palermo, Mario Stanziano, Federico D'Agata, Antonello Galati, Salvatore Gentile, Giancarlo Castellano, Massimo Bartoli, Giuseppina Elena Cipriani, Elisa Rubino, Paolo Fonio, and Innocenzo Rainero
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behavioral variant frontotemporal dementia ,frailty ,magnetic resonance imaging ,voxel-based morphometry ,positron emission tomography ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Frailty is a dynamic clinical condition characterized by the reduction of interconnections among different psychobiological domains, which leads to a homeostatic vulnerability. The association between physical frailty and cognitive dysfunctions is a possible predictor of poor prognosis in patients with neurodegenerative disorders. However, this construct has not been fully analyzed by a multidimensional neuropsychogeriatric assessment matched with multimodal neuroimaging methods in patients with behavioral variant frontotemporal dementia (bvFTD). We have investigated cognitive dysfunctions and frailty status, assessed by both a neuropsychological evaluation and the Multidimensional Prognostic Index (MPI), in a sample of 18 bvFTD patients and compared to matched healthy controls. Gray matter (GM) volume (as assessed by voxel-based morphometry) and metabolism (on 18fluorodeoxyglucose positron emission tomography) were first separately compared between groups, then voxelwise compared and correlated to each other within patients. Linear regression of the MPI was performed on those voxels presenting a significant correlation between altered GM volume and metabolism. The neuropsychological assessment reflected the diagnoses and the functional–anatomical alterations documented by neuroimaging analyses. In particular, the majority of patients presented significant executive dysfunction and mood changes in terms of apathy, depression, and anxiety. In the overall MPI score, the patients fell in the lower range (indicating an early frailty status). On imaging, they exhibited a bilateral decrease of GM density and hypometabolism involving the frontal pole, the anterior opercular region, and the anterior cingulate cortex. Greater atrophy than hypometabolism was observed in the bilateral orbitofrontal cortex, the triangular part of the inferior frontal gyrus, and the ventral striatum, whereas the contrary was detected in the bilateral dorsal anterior cingulate cortex and pre-supplementary motor area. MPI scores significantly correlated only with the co-occurrence of a decrease of GM density and hypometabolism in the right anterior insular cortex, but not with the separate pathological phenomena. Our results show a correlation between a specific pattern of co-occurring GM atrophy and hypometabolism with early frailty in bvFTD patients. These aspects, combined with executive dysfunction and mood changes, may lead to an increased risk of poor prognosis, highlighting a potentially critical and precocious role of the insula in the pathogenesis of frailty.
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- 2021
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12. Pathophysiological Bases of Comorbidity in Migraine
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Claudia Altamura, Ilenia Corbelli, Marina de Tommaso, Cherubino Di Lorenzo, Giorgio Di Lorenzo, Antonio Di Renzo, Massimo Filippi, Tommaso B. Jannini, Roberta Messina, Pasquale Parisi, Vincenzo Parisi, Francesco Pierelli, Innocenzo Rainero, Umberto Raucci, Elisa Rubino, Paola Sarchielli, Linxin Li, Fabrizio Vernieri, Catello Vollono, and Gianluca Coppola
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CNS disorders ,thalamocortical network dysexcitability ,trigeminovascular system ,migraine threshold ,energetic balance ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Despite that it is commonly accepted that migraine is a disorder of the nervous system with a prominent genetic basis, it is comorbid with a plethora of medical conditions. Several studies have found bidirectional comorbidity between migraine and different disorders including neurological, psychiatric, cardio- and cerebrovascular, gastrointestinal, metaboloendocrine, and immunological conditions. Each of these has its own genetic load and shares some common characteristics with migraine. The bidirectional mechanisms that are likely to underlie this extensive comorbidity between migraine and other diseases are manifold. Comorbid pathologies can induce and promote thalamocortical network dysexcitability, multi-organ transient or persistent pro-inflammatory state, and disproportionate energetic needs in a variable combination, which in turn may be causative mechanisms of the activation of an ample defensive system with includes the trigeminovascular system in conjunction with the neuroendocrine hypothalamic system. This strategy is designed to maintain brain homeostasis by regulating homeostatic needs, such as normal subcortico-cortical excitability, energy balance, osmoregulation, and emotional response. In this light, the treatment of migraine should always involves a multidisciplinary approach, aimed at identifying and, if necessary, eliminating possible risk and comorbidity factors.
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- 2021
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13. Being the Family Caregiver of a Patient With Dementia During the Coronavirus Disease 2019 Lockdown
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Milena Zucca, Valeria Isella, Raffaele Di Lorenzo, Camillo Marra, Annachiara Cagnin, Chiara Cupidi, Laura Bonanni, Valentina Laganà, Elisa Rubino, Nicola Vanacore, Federica Agosta, Paolo Caffarra, Renato Sambati, Davide Quaranta, Valeria Guglielmi, Ildebrando M. Appollonio, Giancarlo Logroscino, Massimo Filippi, Gioacchino Tedeschi, Carlo Ferrarese, Innocenzo Rainero, Amalia C. Bruni, and the SINdem COVID-19 Study Group
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caregiver ,dementia ,COVID-19 ,stress ,burden ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Background: Family caregivers of patients with dementia are at high risk of stress and burden, and quarantine due to the coronavirus disease 2019 (COVID-19) pandemic may have increased the risk of psychological disturbances in this population. The current study was carried out during the national lockdown declared in March 2020 by the Italian government as a containment measure of the first wave of the coronavirus pandemic and is the first nationwide survey on the impact of COVID-19 lockdown on the mental health of dementia informal caregivers.Methods: Eighty-seven dementia centers evenly distributed on the Italian territory enrolled 4,710 caregiver–patient pairs. Caregivers underwent a telephone interview assessing classical symptoms of caregiver stress and concern for the consequences of COVID-19 infection on patient’s health. We calculated prevalence of symptoms and regressed them on various potential stress risk factors: caregivers’ sociodemographic characteristics and lifestyle, patients’ clinical features, and lockdown-related elements, like discontinuity in medical care.Results: Approximately 90% of caregivers reported at least one symptom of stress, and nearly 30% reported four or more symptoms. The most prevalent symptoms were concern for consequences of COVID-19 on patient’s health (75%) and anxiety (46%). The main risk factors for stress were identified as a conflicting relationship with the patient and discontinuity in assistance, but caregiver’s female sex, younger age, lower education, and cohabitation with the patient also had an impact. Availability of help from institutions or private individuals showed a protective effect against sense of abandonment but a detrimental effect on concern about the risk for the patient to contract COVID-19. The only protective factor was mild dementia severity, which was associated with a lower risk of feeling isolated and abandoned; type of dementia, on the other hand, did not affect stress risk.Conclusion: Our results demonstrate the large prevalence of stress in family caregivers of patients with dementia during the COVID-19 pandemic and have identified both caregivers and situations at a higher risk of stress, which should be taken into account in the planning of interventions in support of quarantined families and patients.
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- 2021
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14. Consistent effects of non-invasive vagus nerve stimulation (nVNS) for the acute treatment of migraine: additional findings from the randomized, sham-controlled, double-blind PRESTO trial
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Paolo Martelletti, Piero Barbanti, Licia Grazzi, Giulia Pierangeli, Innocenzo Rainero, Pierangelo Geppetti, Anna Ambrosini, Paola Sarchielli, Cristina Tassorelli, Eric Liebler, Marina de Tommaso, and on Behalf of the PRESTO Study Group
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Neuromodulation ,Vagus nerve stimulation ,Migraine ,Pain intensity ,Double-blind ,Open-label ,Medicine - Abstract
Abstract Background Non-invasive vagus nerve stimulation (nVNS) has been shown to be practical, safe, and well tolerated for treating primary headache disorders. The recent multicenter, randomized, double-blind, sham-controlled PRESTO trial provided Class I evidence that for patients with episodic migraine, nVNS significantly increases the probability of having mild pain or being pain-free 2 h post stimulation. We report additional pre-defined secondary and other end points from PRESTO that demonstrate the consistency and durability of nVNS efficacy across a broad range of outcomes. Methods After a 4-week observation period, 248 patients with episodic migraine with/without aura were randomly assigned to acute treatment of migraine attacks with nVNS (n = 122) or a sham device (n = 126) during a double-blind period lasting 4 weeks (or until the patient had treated 5 attacks). All patients received nVNS therapy during the subsequent 4-week/5-attack open-label period. Results The intent-to-treat population consisted of 243 patients. The nVNS group (n = 120) had a significantly greater percentage of attacks treated during the double-blind period that were pain-free at 60 (P = 0.005) and 120 min (P = 0.026) than the sham group (n = 123) did. Similar results were seen for attacks with pain relief at 60 (P = 0.025) and 120 min (P = 0.018). For the first attack and all attacks, the nVNS group had significantly greater decreases (vs sham) in pain score from baseline to 60 min (P = 0.029); the decrease was also significantly greater for nVNS at 120 min for the first attack (P = 0.011). Results during the open-label period were consistent with those of the nVNS group during the double-blind period. The incidence of adverse events (AEs) and adverse device effects was low across all study periods, and no serious AEs occurred. Conclusions These results further demonstrate that nVNS is an effective and reliable acute treatment for multiple migraine attacks, which can be used safely while preserving the patient’s option to use traditional acute medications as rescue therapy, possibly decreasing the risk of medication overuse. Together with its practicality and optimal tolerability profile, these findings suggest nVNS has value as a front-line option for acute treatment of migraine. Trial registration ClinicalTrials.gov identifier: NCT02686034.
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- 2018
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15. Practical and clinical utility of non-invasive vagus nerve stimulation (nVNS) for the acute treatment of migraine: a post hoc analysis of the randomized, sham-controlled, double-blind PRESTO trial
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Licia Grazzi, Cristina Tassorelli, Marina de Tommaso, Giulia Pierangeli, Paolo Martelletti, Innocenzo Rainero, Pierangelo Geppetti, Anna Ambrosini, Paola Sarchielli, Eric Liebler, Piero Barbanti, and on Behalf of the PRESTO Study Group
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Neuromodulation ,Vagus nerve stimulation ,Post hoc analysis ,Migraine ,Rescue medication ,Pain intensity ,Medicine - Abstract
Abstract Background The PRESTO study of non-invasive vagus nerve stimulation (nVNS; gammaCore®) featured key primary and secondary end points recommended by the International Headache Society to provide Class I evidence that for patients with an episodic migraine, nVNS significantly increases the probability of having mild pain or being pain-free 2 h post stimulation. Here, we examined additional data from PRESTO to provide further insights into the practical utility of nVNS by evaluating its ability to consistently deliver clinically meaningful improvements in pain intensity while reducing the need for rescue medication. Methods Patients recorded pain intensity for treated migraine attacks on a 4-point scale. Data were examined to compare nVNS and sham with regard to the percentage of patients who benefited by at least 1 point in pain intensity. We also assessed the percentage of attacks that required rescue medication and pain-free rates stratified by pain intensity at treatment initiation. Results A significantly higher percentage of patients who used acute nVNS treatment (n = 120) vs sham (n = 123) reported a ≥ 1-point decrease in pain intensity at 30 min (nVNS, 32.2%; sham, 18.5%; P = 0.020), 60 min (nVNS, 38.8%; sham, 24.0%; P = 0.017), and 120 min (nVNS, 46.8%; sham, 26.2%; P = 0.002) after the first attack. Similar significant results were seen when assessing the benefit in all attacks. The proportion of patients who did not require rescue medication was significantly higher with nVNS than with sham for the first attack (nVNS, 59.3%; sham, 41.9%; P = 0.013) and all attacks (nVNS, 52.3%; sham, 37.3%; P = 0.008). When initial pain intensity was mild, the percentage of patients with no pain after treatment was significantly higher with nVNS than with sham at 60 min (all attacks: nVNS, 37.0%; sham, 21.2%; P = 0.025) and 120 min (first attack: nVNS, 50.0%; sham, 25.0%; P = 0.018; all attacks: nVNS, 46.7%; sham, 30.1%; P = 0.037). Conclusions This post hoc analysis demonstrated that acute nVNS treatment quickly and consistently reduced pain intensity while decreasing rescue medication use. These clinical benefits provide guidance in the optimal use of nVNS in everyday practice, which can potentially reduce use of acute pharmacologic medications and their associated adverse events. Trial registration ClinicalTrials.gov identifier: NCT02686034.
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- 2018
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16. Machine Learning Profiling of Alzheimer's Disease Patients Based on Current Cerebrospinal Fluid Markers and Iron Content in Biofluids
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Eleonora Ficiarà, Silvia Boschi, Shoeb Ansari, Federico D'Agata, Ornella Abollino, Paola Caroppo, Giuseppe Di Fede, Antonio Indaco, Innocenzo Rainero, and Caterina Guiot
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cerebrospinal fluid ,iron ,biomarker (BM) ,mild cognitive impairment ,Alzheimer's disease ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Alzheimer's disease (AD) is the most common form of dementia, characterized by a complex etiology that makes therapeutic strategies still not effective. A true understanding of key pathological mechanisms and new biomarkers are needed, to identify alternative disease-modifying therapies counteracting the disease progression. Iron is an essential element for brain metabolism and its imbalance is implicated in neurodegeneration, due to its potential neurotoxic effect. However, the role of iron in different stages of dementia is not clearly established. This study aimed to investigate the potential impact of iron both in cerebrospinal fluid (CSF) and in serum to improve early diagnosis and the related therapeutic possibility. In addition to standard clinical method to detect iron in serum, a precise quantification of total iron in CSF was performed using graphite-furnace atomic absorption spectrometry in patients affected by AD, mild cognitive impairment, frontotemporal dementia, and non-demented neurological controls. The application of machine learning techniques, such as clustering analysis and multiclassification algorithms, showed a new potential stratification of patients exploiting iron-related data. The results support the involvement of iron dysregulation and its potential interaction with biomarkers (Tau protein and Amyloid-beta) in the pathophysiology and progression of dementia.
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- 2021
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17. The Impact of COVID-19 Quarantine on Patients With Dementia and Family Caregivers: A Nation-Wide Survey
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Innocenzo Rainero, Amalia C. Bruni, Camillo Marra, Annachiara Cagnin, Laura Bonanni, Chiara Cupidi, Valentina Laganà, Elisa Rubino, Alessandro Vacca, Raffaele Di Lorenzo, Paolo Provero, Valeria Isella, Nicola Vanacore, Federica Agosta, Ildebrando Appollonio, Paolo Caffarra, Cinzia Bussè, Renato Sambati, Davide Quaranta, Valeria Guglielmi, Giancarlo Logroscino, Massimo Filippi, Gioacchino Tedeschi, Carlo Ferrarese, the SINdem COVID-19 Study Group, Erica Gallo, Alberto Grassini, Andrea Marcinnò, Fausto Roveta, Paola De Martino, Francesca Frangipane, Gianfranco Puccio, Rosanna Colao, Maria Mirabelli, Chiara Terracciano, Federica Lino, Stefano Mozzetta, Gianmarco Gazzola, Giulia Camporese, Simona Sacco, Maria Carmela Lechiara, Claudia Carrarini, Mirella Russo, Alfonsina Casa lena, Patrizia Sucapane, Pietro Tiraboschi, Paola Caroppo, Veronica Redaelli, Giuseppe Di Fede, Daniela Coppa, Lenino Peluso, Pasqualina Insarda, Matteo De Bartolo, Sabrina Esposito, Alessandro Iavarone, Carmine Fuschillo, Elena Salvatore, Chiara Criscuolo, Luisa Sambati, Rossella Santoro, Daniela Gragnaniello, Ilaria Pedriali, Livia Ludovico, Annalisa Chiari, Andrea Fabbo, Petra Bevilacqua, Chiara Galli, Silvia Magarelli, Gianfranco Spalletta, Nerisa Banaj, Giulia Caruso, Desirée Estela Porcari, Franco Giubilei, Anna Rosa Casini, Francesca Ursini, Giuseppe Bruno, Stefano Boffelli, Michela Brambilla, Giuseppe Magnani, Francesca Caso, Edoardo G. Spinelli, Elena Sinforiani, Alfredo Costa, Simona Luzzi, Gabriella Cacchiò, A.I.M.A. –sez Parma, Marta Perini, Rossano Angeloni, Cinzia Giuli, Katia Fabi, Marco Guidi, Cristina Paci, Annaelisa Castellano, Elena Carapelle, Rossella Petrucci, Miriam Accogli, Giovanna Nicoletta Trevisi, Serena Renna, Antonella Vasquez Giuliano, Fulvio Da Re, Antonio Milia, Giuseppina Pilia, Maria Giuseppina Mascia, Valeria Putzu, Tommaso Piccoli, Luca Cuffaro, Roberto Monastero, Antonella Battaglia, Valeria Blandino, Federica Lupo, Eduardo Cumbo, Antonina Luca, Giuseppe Caravaglios, Annalisa Vezzosi, Valentina Bessi, Gloria Tognoni, Valeria Calsolaro, Giulia Lucarelli, Serena Amici, Alberto Trequattrini, Salvatore Pezzuto, Patrizia Mecocci, Giulia Caironi, Barbara Boselli, Marino Formilan, Alessandra Coin, Laura De Togni, Francesca Sala, Giulia Sandri, Maurizio Gallucci, Anna Paola Mazzarolo, Cristina Bergamelli, and Serena Passoni
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quarantine ,COVID-19 ,dementia ,Alzheimer’s disease ,BPSD ,caregiver burden ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
IntroductionPrevious studies showed that quarantine for pandemic diseases is associated with several psychological and medical effects. The consequences of quarantine for COVID-19 pandemic in patients with dementia are unknown. We investigated the clinical changes in patients with Alzheimer’s disease and other dementias, and evaluated caregivers’ distress during COVID-19 quarantine.MethodsThe study involved 87 Italian Dementia Centers. Patients with Alzheimer’s Disease (AD), Dementia with Lewy Bodies (DLB), Frontotemporal Dementia (FTD), and Vascular Dementia (VD) were eligible for the study. Family caregivers of patients with dementia were interviewed by phone in April 2020, 45 days after quarantine declaration. Main outcomes were patients’ changes in cognitive, behavioral, and motor symptoms. Secondary outcomes were effects on caregivers’ psychological features.Results4913 patients (2934 females, 1979 males) fulfilled the inclusion criteria. Caregivers reported a worsening in cognitive functions in 55.1% of patients, mainly in subjects with DLB and AD. Aggravation of behavioral symptoms was observed in 51.9% of patients. In logistic regression analysis, previous physical independence was associated with both cognitive and behavioral worsening (odds ratio 1.85 [95% CI 1.42–2.39], 1.84 [95% CI 1.43–2.38], respectively). On the contrary, pandemic awareness was a protective factor for the worsening of cognitive and behavioral symptoms (odds ratio 0.74 [95% CI 0.65–0.85]; and 0.72 [95% CI 0.63–0.82], respectively). Approximately 25.9% of patients showed the onset of new behavioral symptoms. A worsening in motor function was reported by 36.7% of patients. Finally, caregivers reported a high increase in anxiety, depression, and distress.ConclusionOur study shows that quarantine for COVID-19 is associated with an acute worsening of clinical symptoms in patients with dementia as well as increase of caregivers’ burden. Our findings emphasize the importance to implement new strategies to mitigate the effects of quarantine in patients with dementia.
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- 2021
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18. Investigating the Effects of COVID-19 Quarantine in Migraine: An Observational Cross-Sectional Study From the Italian National Headache Registry (RICe)
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Marianna Delussi, Eleonora Gentile, Gianluca Coppola, Addolorata Maria Pia Prudenzano, Innocenzo Rainero, Grazia Sances, Chiara Abagnale, Valeria Caponnetto, Francesco De Cesaris, Ilaria Frattale, Elena Guaschino, Andrea Marcinnò, Raffaele Ornello, Francesca Pistoia, Alessia Putortì, Maria Elena Roca, Fausto Roveta, Chiara Lupi, Maria Trojano, Francesco Pierelli, Pierangelo Geppetti, Simona Sacco, and Marina de Tommaso
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migraine ,COVID-19 ,lockdown ,resilience ,disgust ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Background: Previous studies during SARS and Ebola pandemics have shown that quarantine is associated with several negative psychological effects, such as post-traumatic stress symptoms, confusion, and anger. These conditions may affect the course of many diseases, including migraine. Although it is possible that the quarantine measures for the current COVID-19 pandemic affect migraine burden, no information is currently available on this issue.Aim: In this study, we aimed to: (1) explore the possible changes in migraine frequency, severity, and days with acute medication intake during quarantine period; (2) evaluate possible differences in migraine outcomes in consideration of lifestyle changes, emotions, pandemic diffusion, and COVID-19 infection.Methods: We interviewed patients who were included in the observational Italian Headache Registry (Registro Italiano Cefalee, RICE), retrospectively collecting information on main headache features, lifestyle factors, emotions, individual infection status, and perception of COVID-19 for 2 months before (pre-quarantine) and after the beginning of the quarantine (quarantine). Inclusion criteria were: age > 18, diagnosis of migraine without aura, migraine with aura and chronic migraine, last in-person visit more than 3 months preceding the beginning of quarantine.Results: A total of 433 migraine subjects agreed to be interviewed. We found an overall reduction in headache frequency (9.42 ± 0.43 days with headache vs. 8.28 ± 0.41) and intensity (6.57 ± 0.19 vs. 6.59 ± 0.21) during the quarantine, compared to pre-quarantine. There was a correlation between improvement and number of days of stay-at-home. When results were stratified for geographic area, we found a tendency toward worsening of headache frequency in northern Italy. Disgust regarding viral infection corresponded to a minor improvement in migraine.Conclusions: Migraine patients showed a mild improvement of migraine features, probably attributable to resilient behavior toward pandemic distress. Disgust regarding the contagion whereas potentially favoring defensive behavior, could potentially worsen migraine. The spontaneous limitation of migraine burden during quarantine could favor patient follow-up via the use of telemedicine visits, reliable diaries, and frequent remote contacts.
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- 2020
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19. Behavioral and Psychological Effects of Coronavirus Disease-19 Quarantine in Patients With Dementia
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Annachiara Cagnin, Raffaele Di Lorenzo, Camillo Marra, Laura Bonanni, Chiara Cupidi, Valentina Laganà, Elisa Rubino, Alessandro Vacca, Paolo Provero, Valeria Isella, Nicola Vanacore, Federica Agosta, Ildebrando Appollonio, Paolo Caffarra, Ilaria Pettenuzzo, Renato Sambati, Davide Quaranta, Valeria Guglielmi, Giancarlo Logroscino, Massimo Filippi, Gioacchino Tedeschi, Carlo Ferrarese, Innocenzo Rainero, Amalia C. Bruni, SINdem COVID-19 Study Group, Erica Gallo, Alberto Grassini, Andrea Marcinnò, Fausto Roveta, Paola De Martino, Francesca Frangipane, Gianfranco Puccio, Rosanna Colao, Maria Mirabelli, Noemi Martellacci, Federica Lino, Stefano Mozzetta, Cinzia Bussè, Giulia Camporese, Simona Sacco, Maria Carmela Lechiara, Claudia Carrarini, Mirella Russo, Alfonsina Casalena, Patrizia Sucapane, Pietro Tiraboschi, Paola Caroppo, Veronica Redaelli, Giuseppe Di Fede, Daniela Coppa, Lenino Peluso, Pasqualina Insarda, Matteo De Bartolo, Sabrina Esposito, Alessandro Iavarone, Anna Vittoria Marta Orsini, Elena Salvatore, Chiara Criscuolo, Luisa Sambati, Rossella Santoro, Daniela Gragnaniello, Ilaria Pedriali, Livia Ludovico, Annalisa Chiari, Andrea Fabbo, Petra Bevilacqua, Chiara Galli, Silvia Magarelli, Marta Perini, Gianfranco Spalletta, Nerisa Banaj, Desirée Estela Porcari, Giulia Caruso, Virginia Cipollini, Anna Rosa Casini, Francesca Ursini, Giuseppe Bruno, Renzo Rozzini, Michela Brambilla, Giuseppe Magnani, Francesca Caso, Edoardo G. Spinelli, Matteo Cotta Ramusino, Giulia Perini, Simona Luzzi, Gabriella Cacchiò, Rossano Angeloni, Cinzia Giuli, Katia Fabi, Marco Guidi, Cristina Paci, Annaelisa Castellano, Elena Carapelle, Rossella Petrucci, Miriam Accogli, Gianluigi Calabrese, Giovanna Nicoletta Trevisi, Brigida Coluccia, Antonella Vasquez Giuliano, Marcella Caggiula, Fulvio Da Re, Antonio Milia, Giuseppina Pilia, Maria Giuseppina Mascia, Valeria Putzu, Tommaso Piccoli, Luca Cuffaro, Roberto Monastero, Antonella Battaglia, Valeria Blandino, Federica Lupo, Eduardo Cumbo, Luca Antonina, Giuseppe Caravaglios, Annalisa Vezzosi, Valentina Bessi, Gloria Tognoni, Valeria Calsolaro, Enrico Mossello, Serena Amici, Alberto Trequattrini, Salvatore Pezzuto, Patrizia Mecocci, Giulia Fichera, Samantha Pradelli, Marino Formilan, Alessandra Coin, Laura Detogni, Francesca Sala, Giulia Sandri, Maurizio Gallucci, Anna Paola Mazzarolo, and Cristina Bergamelli
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behavioral and psychological symptoms ,behavioral symptoms ,psychological symptoms ,quarantine ,dementia ,caregiver ,Psychiatry ,RC435-571 - Abstract
BackgroundIn March 2020, the World Health Organization declared a global pandemic due to the novel coronavirus SARS-CoV-2 and several governments planned a national quarantine in order to control the virus spread. Acute psychological effects of quarantine in frail elderly subjects with special needs, such as patients with dementia, have been poorly investigated. The aim of this study was to assess modifications of neuropsychiatric symptoms during quarantine in patients with dementia and their caregivers.MethodsThis is a sub-study of a multicenter nation-wide survey. A structured telephone interview was delivered to family caregivers of patients with diagnosis of Alzheimer disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and vascular dementia (VD), followed regularly at 87 Italian memory clinics. Variations in behavioral and psychological symptoms (BPSD) were collected after 1 month since quarantine declaration and associations with disease type, severity, gender, and caregiver’s stress burden were analyzed.ResultsA total of 4,913 caregivers participated in the survey. Increased BPSD was reported in 59.6% of patients as worsening of preexisting symptoms (51.9%) or as new onset (26%), and requested drug modifications in 27.6% of these cases. Irritability, apathy, agitation, and anxiety were the most frequently reported worsening symptoms and sleep disorder and irritability the most frequent new symptoms. Profile of BPSD varied according to dementia type, disease severity, and patients’ gender. Anxiety and depression were associated with a diagnosis of AD (OR 1.35, CI: 1.12–1.62), mild to moderate disease severity and female gender. DLB was significantly associated with a higher risk of worsening hallucinations (OR 5.29, CI 3.66–7.64) and sleep disorder (OR 1.69, CI 1.25–2.29), FTD with wandering (OR 1.62, CI 1.12–2.35), and change of appetite (OR 1.52, CI 1.03–2.25). Stress-related symptoms were experienced by two-thirds of caregivers and were associated with increased patients’ neuropsychiatric burden (p
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- 2020
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20. Migraine during COVID-19: Data from Second Wave Pandemic in an Italian Cohort
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Eleonora Gentile, Marianna Delussi, Chiara Abagnale, Valeria Caponnetto, Francesco De Cesaris, Ilaria Frattale, Elena Guaschino, Andrea Marcinnò, Raffaele Ornello, Francesca Pistoia, Alessia Putortì, Giusy Candida, Fausto Roveta, Chiara Lupi, Gianluca Coppola, Addolorata Maria Pia Prudenzano, Innocenzo Rainero, Grazia Sances, Maria Elena Roca, Maria Trojano, Francesco Pierelli, Pierangelo Geppetti, Simona Sacco, and Marina de Tommaso
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migraine ,COVID-19 ,second wave pandemic ,headache frequency ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Objectives: The study aims to assess the impact of the second COVID-19 pandemic wave on migraine characteristics. Methods: This is an observational cross-sectional study conducted on migraine patients previously interviewed during the first Italian pandemic outbreak. A second structured telephone interview was conducted between 20 November 2020 and 18 January 2021. We compared migraine characteristics among T0 (before pandemic), T1 (during the first pandemic phase), and T2 (during the second pandemic phase). Results: Among the 433 patients interviewed during the first pandemic phase, 304 cases were finally considered. One hundred forty-eight patients had a control visit between March 2020 and December 2020, 120 had an in-person visit, 14 by phone, the remainder used telemedicine software provided by the hospital. Frequency of headache, number of symptomatic drugs and headache intensity worsened during T2, compared to T0 and T1, especially in episodic migraine. Headache intensity increased relating to the negative emotional impact of the pandemic. Migraine management during the pandemic did not influence the clinical outcome. Conclusion: The prolongation of the pandemic seems to have a negative impact on migraine evolution. The arousal and negative psychological behavior toward the COVID-19 outbreak seem to worsen migraine.
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- 2021
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21. Robots in Elderly Care
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Alessandro Vercelli, Innocenzo Rainero, Ludovico Ciferri, Marina Boido, and Fabrizio Pirri
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Sociology (General) ,HM401-1281 - Abstract
Low birth rate and the long life expectancy represent an explosive mixture, resulting in the rapid aging of population. The costs of healthcare in the grey society are increasing dramatically, and soon there will be not enough resources and people for care. This context requires conceptually new elderly care solutions progressively reducing the percentages of the human-based care. Research on robot-based solutions for elderly care and active ageing aims to answer these needs. From a general perspective, robotics has the power to completely reshape the landscape of healthcare both in its structure and its operation. In fact, the long-term sustainability of healthcare systems could be addressed by automation powered by digital health technologies, such as artificial intelligence, 3D-printing or robotics. The latter could take over monotonous work from healthcare workers, which would allow them to focus more on patients and to have lesser workload. Robots might be used in elder care with several different aims. (i) Robots may act as caregivers, i.e. assist the elderly, (ii) they can provide remainders and instructions for activities of daily life and safety, and/or assist their carers in daily tasks; (iii) they can help monitor their behaviour and health; and (iv) provide companionship, including entertainment and hobbies, reminiscence and social contact. The use of Robots with human subjects/patients raise several sensitive questions. First of all, robots may represent information hubs, and can collect an incredible amount of data about the subjects and their environment. In fact, they record habits such as sleeping, exercising, third persons entering in the house, appointments. Communications may be continuously recorded. Moreover, by connecting with medical devices, they can store medical data. On one hand, this represents a very powerful tool to collect information about the single subject (precision medicine), about disease (thus eventually finding new signs and symptoms through artificial intelligence by machine learning and deep learning) and about his/her habitat. On the other, this powerful instrument may represent a dramatic treat to the privacy of the subjects and their caregivers. Therefore, robotics represents an ethically sensitive field. Care robotics bear the risk of reducing human contact, of increasing the objectification and loss of control of the elderly, of losing the privacy and personal freedom of the individual (especially when robots may perform restrictive interventions). Moreover, the use of robots in elderly care may raise in the risk of confusing between reality and appearance, with a potential risk of deception and infantilization of the elder.
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- 2018
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22. Neuropsychological Correlates of Pre-Frailty in Neurocognitive Disorders: A Possible Role for Metacognitive Dysfunction and Mood Changes
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Martina Amanzio, Sara Palermo, Milena Zucca, Rosalba Rosato, Elisa Rubino, Daniela Leotta, Massimo Bartoli, and Innocenzo Rainero
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pre-frailty ,mild cognitive impairment ,comprehensive geriatric assessment ,Alzheimer’s disease ,executive dysfunction ,Medicine (General) ,R5-920 - Abstract
BackgroundRecent studies have suggested that cognitive functions in patients with neurocognitive disorders have a significant role in the pathogenic mechanisms of frailty. Although pre-frailty is considered an intermediate, preclinical state, epidemiological research has begun to dislodge cognition and frailty into their specific subcomponents to understand the relationship among them. We aim to analyse the possible association between pre-frailty and neuropsychological variables to outline which factors can contribute to minor and major neurocognitive disorders.Methods60 subjects complaining of different cognitive deficits underwent a deep-in-wide frailty and neuropsychological assessment. We conducted three multiple linear regression analyses adjusted for a combination of demographic measures and involving several neuropsychological–behavioural parameters selected by the literature on physical frailty.ResultsWe found a significant association between frailty—as measured by the multidimensional prognostic index (MPI)—and action monitoring and monetary gain (cognitive domain), depression and disinhibition (behavioural domain). Moreover, an association between MPI and impaired awareness for instrumental activities disabilities exists.ConclusionWe propose a novel framework for understanding frailty associated with metacognitive–executive dysfunction.
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- 2017
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23. Correction to: Consistent effects of non-invasive vagus nerve stimulation (nVNS) for the acute treatment of migraine: additional findings from the randomized, sham-controlled, double-blind PRESTO trial
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Paolo Martelletti, Piero Barbanti, Licia Grazzi, Giulia Pierangeli, Innocenzo Rainero, Pierangelo Geppetti, Anna Ambrosini, Paola Sarchielli, Cristina Tassorelli, Eric Liebler, Marina de Tommaso, and on Behalf of the PRESTO Study Group
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Medicine - Abstract
Following publication of the original article [1], the authors notified us o that the Table 1 citation within the legend was not presented as initially requested.
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- 2018
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24. A novel network analysis approach reveals DNA damage, oxidative stress and calcium/cAMP homeostasis-associated biomarkers in frontotemporal dementia.
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Fernando Palluzzi, Raffaele Ferrari, Francesca Graziano, Valeria Novelli, Giacomina Rossi, Daniela Galimberti, Innocenzo Rainero, Luisa Benussi, Benedetta Nacmias, Amalia C Bruni, Daniele Cusi, Erika Salvi, Barbara Borroni, and Mario Grassi
- Subjects
Medicine ,Science - Abstract
Frontotemporal Dementia (FTD) is the form of neurodegenerative dementia with the highest prevalence after Alzheimer's disease, equally distributed in men and women. It includes several variants, generally characterized by behavioural instability and language impairments. Although few mendelian genes (MAPT, GRN, and C9orf72) have been associated to the FTD phenotype, in most cases there is only evidence of multiple risk loci with relatively small effect size. To date, there are no comprehensive studies describing FTD at molecular level, highlighting possible genetic interactions and signalling pathways at the origin FTD-associated neurodegeneration. In this study, we designed a broad FTD genetic interaction map of the Italian population, through a novel network-based approach modelled on the concepts of disease-relevance and interaction perturbation, combining Steiner tree search and Structural Equation Model (SEM) analysis. Our results show a strong connection between Calcium/cAMP metabolism, oxidative stress-induced Serine/Threonine kinases activation, and postsynaptic membrane potentiation, suggesting a possible combination of neuronal damage and loss of neuroprotection, leading to cell death. In our model, Calcium/cAMP homeostasis and energetic metabolism impairments are primary causes of loss of neuroprotection and neural cell damage, respectively. Secondly, the altered postsynaptic membrane potentiation, due to the activation of stress-induced Serine/Threonine kinases, leads to neurodegeneration. Our study investigates the molecular underpinnings of these processes, evidencing key genes and gene interactions that may account for a significant fraction of unexplained FTD aetiology. We emphasized the key molecular actors in these processes, proposing them as novel FTD biomarkers that could be crucial for further epidemiological and molecular studies.
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- 2017
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25. Correction to: Practical and clinical utility of non-invasive vagus nerve stimulation (nVNS) for the acute treatment of migraine: a post hoc analysis of the randomized, sham-controlled, double-blind PRESTO trial
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Licia Grazzi, Cristina Tassorelli, Marina de Tommaso, Giulia Pierangeli, Paolo Martelletti, Innocenzo Rainero, Pierangelo Geppetti, Anna Ambrosini, Paola Sarchielli, Eric Liebler, Piero Barbanti, and on Behalf of the PRESTO Study Group
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Medicine - Abstract
Following publication of the original article [1], the authors notified us that a part of the Figure 3 legend was omitted during proofing stage.
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- 2019
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26. Magnetic Nanoparticles in the Central Nervous System: Targeting Principles, Applications and Safety Issues
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Federico D’Agata, Federico Alessandro Ruffinatti, Silvia Boschi, Ilaria Stura, Innocenzo Rainero, Ornella Abollino, Roberta Cavalli, and Caterina Guiot
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magnetic nanoparticles ,targeting ,delivery ,central nervous system ,blood brain barrier ,Organic chemistry ,QD241-441 - Abstract
One of the most challenging goals in pharmacological research is overcoming the Blood Brain Barrier (BBB) to deliver drugs to the Central Nervous System (CNS). The use of physical means, such as steady and alternating magnetic fields to drive nanocarriers with proper magnetic characteristics may prove to be a useful strategy. The present review aims at providing an up-to-date picture of the applications of magnetic-driven nanotheranostics agents to the CNS. Although well consolidated on physical ground, some of the techniques described herein are still under investigation on in vitro or in silico models, while others have already entered in—or are close to—clinical validation. The review provides a concise overview of the physical principles underlying the behavior of magnetic nanoparticles (MNPs) interacting with an external magnetic field. Thereafter we describe the physiological pathways by which a substance can reach the brain from the bloodstream and then we focus on those MNP applications that aim at a nondestructive crossing of the BBB such as static magnetic fields to facilitate the passage of drugs and alternating magnetic fields to increment BBB permeability by magnetic heating. In conclusion, we briefly cite the most notable biomedical applications of MNPs and some relevant remarks about their safety and potential toxicity.
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- 2017
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27. Orexin Receptor Multimerization versus Functional Interactions: Neuropharmacological Implications for Opioid and Cannabinoid Signalling and Pharmacogenetics
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Miles D. Thompson, Takeshi Sakurai, Innocenzo Rainero, Mary C. Maj, and Jyrki P. Kukkonen
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orexin/hypocretin ,OX1 orexin receptor ,OX2 orexin receptor ,homo-dimerization ,hetero-dimerization ,opioid receptor ,CB1 cannabinoid receptor ,status epilepticus ,feeding behavior ,sleep disorder ,Medicine ,Pharmacy and materia medica ,RS1-441 - Abstract
Orexins/hypocretins are neuropeptides formed by proteolytic cleavage of a precursor peptide, which are produced by neurons found in the lateral hypothalamus. The G protein-coupled receptors (GPCRs) for these ligands, the OX1 and OX2 orexin receptors, are more widely expressed throughout the central nervous system. The orexin/hypocretin system has been implicated in many pathways, and its dysregulation is under investigation in a number of diseases. Disorders in which orexinergic mechanisms are being investigated include narcolepsy, idiopathic sleep disorders, cluster headache and migraine. Human narcolepsy has been associated with orexin deficiency; however, it has only rarely been attributed to mutations in the gene encoding the precursor peptide. While gene variations within the canine OX2 gene hcrtr2 have been directly linked with narcolepsy, the majority of human orexin receptor variants are weakly associated with diseases (the idiopathic sleep disorders, cluster headache and polydipsia-hyponatremia in schizophrenia) or are of potential pharmacogenetic significance. Evidence for functional and/or heterodimerization between wild-type variant orexin receptors and opioid and cannabinoid receptors is discussed in the context of its relevance to depression and epilepsy.
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- 2017
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28. Neurofunctional Signature of Hyperfamiliarity for Unknown Faces.
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Elisa Negro, Federico D'Agata, Paola Caroppo, Mario Coriasco, Federica Ferrio, Alessia Celeghin, Matteo Diano, Elisa Rubino, Beatrice de Gelder, Innocenzo Rainero, Lorenzo Pinessi, and Marco Tamietto
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Medicine ,Science - Abstract
Hyperfamiliarity for unknown faces is a rare selective disorder that consists of the disturbing and abnormal feeling of familiarity for unknown faces, while recognition of known faces is normal. In one such patient we investigated with a multimodal neuroimaging design the hitherto undescribed neural signature associated with hyperfamiliarity feelings. Behaviorally, signal detection methods revealed that the patient's discrimination sensitivity between familiar and unfamiliar faces was significantly lower than that of matched controls, and her response criterion for familiarity decisions was significantly more liberal. At the neural level, while morphometric analysis and single-photon emission CT (SPECT) showed the atrophy and hypofunctioning of the left temporal regions, functional magnetic resonance imaging (fMRI) revealed that hyperfamiliarity feelings were selectively associated to enhanced activity in the right medial and inferior temporal cortices. We therefore characterize the neurofunctional signature of hyperfamiliarity for unknown faces as related to the loss of coordinated activity between the complementary face processing functions of the left and right temporal lobes.
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- 2015
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29. A mathematical model for the evaluation of iron transport across the blood-cerebrospinal fluid barrier in neurodegenerative diseases.
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Eleonora Ficiarà, Federico D'Agata, Sardar Ansari, Silvia Boschi, Innocenzo Rainero, Lorenzo Priano, Stefania Cattaldo, Ornella Abollino, Roberta Cavalli, and Caterina Guiot
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- 2020
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30. A Novel PSEN1 Variant Leading to Posterior Cortical Atrophy: A Case Report
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Fausto Roveta, Andrea Marcinnò, Alberto Grassini, Fabio Ferrandes, Aurora Cermelli, Silvia Boschi, Salvatore Gallone, Cristiana Atzori, Daniele Imperiale, Patrizia Dentelli, Barbara Pasini, Alfredo Brusco, Elisa Rubino, and Innocenzo Rainero
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Psychiatry and Mental health ,Clinical Psychology ,General Neuroscience ,Geriatrics and Gerontology - Abstract
We describe a 52-year-old patient with a progressive visuospatial disorder and apraxia. Neuropsychological assessment, neuroradiological findings, and Alzheimer’s disease (AD) core biomarker assay on cerebrospinal fluid led to a diagnosis of posterior cortical atrophy due to AD. We performed a next generation sequencing dementia-gene panel and found the c.1301 C>T p.(Ala434Val) variant in the Presenilin1 (PSEN1) gene. The missense change affects the PAL (Pro433-Ala434-Leu435) motif critical for catalytic activity of the macromolecular γ-secretase complex. Evolutionary and integrated bioinformatic tools predicted a deleterious effect of the variant supporting its role in the AD pathogenesis.
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- 2023
31. Dementia, infections and vaccines: 30 years of controversy
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Fiona Ecarnot, Virginia Boccardi, Andrea Calcagno, Claudio Franceschi, Tamas Fülop, Ruth F. Itzhaki, Jean-Pierre Michel, Francesco Panza, Innocenzo Rainero, Vincenzo Solfrizzi, Andrea Ticinesi, Nicola Veronese, and Stefania Maggi
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Aging ,Geriatrics and Gerontology - Abstract
This paper reports the proceedings of a virtual meeting convened by the European Interdisciplinary Council on Ageing (EICA), to discuss the involvement of infectious disorders in the pathogenesis of dementia and neurological disorders leading to dementia. We recap how our view of the infectious etiology of dementia has changed over the last 30 years in light of emerging evidence, and we present evidence in support of the implication of infection in dementia, notably Alzheimer’s disease (AD). The bacteria and viruses thought to be responsible for neuroinflammation and neurological damage are reviewed. We then review the genetic basis for neuroinflammation and dementia, highlighting the genes that are currently the focus of investigation as potential targets for therapy. Next, we describe the antimicrobial hypothesis of dementia, notably the intriguing possibility that amyloid beta may itself possess antimicrobial properties. We further describe the clinical relevance of the gut–brain axis in dementia, the mechanisms by which infection can move from the intestine to the brain, and recent findings regarding dysbiosis patterns in patients with AD. We review the involvement of specific pathogens in neurological disorders, i.e. SARS-CoV-2, human immunodeficiency virus (HIV), herpes simplex virus type 1 (HSV1), and influenza. Finally, we look at the role of vaccination to prevent dementia. In conclusion, there is a large body of evidence supporting the involvement of various infectious pathogens in the pathogenesis of dementia, but large-scale studies with long-term follow-up are needed to elucidate the role that infection may play, especially before subclinical or clinical disease is present.
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- 2023
32. My-active and healthy ageing (My-AHA): An ICT platform to detect frailty risk and propose intervention.
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Alessandro Vercelli, Innocenzo Rainero, Helios de Rosario, Mathew Summers, Rainer Wieching, Georg Aumayr, Stephan Bandelow, Ludovico Ciferri, and Marco Bazzani
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- 2017
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33. Aβ42 as a Biomarker of Alzheimer’s Disease: Is Saliva a Viable Alternative to Cerebrospinal Fluid?
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Rubino, Silvia Boschi, Fausto Roveta, Alberto Grassini, Andrea Marcinnò, Aurora Cermelli, Fabio Ferrandes, Innocenzo Rainero, and Elisa
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saliva ,CSF ,beta amyloid 42 ,Alzheimer’s disease ,biomarkers - Abstract
The identification of reliable biomarkers in biological fluids is paramount to optimizing the diagnosis of Alzheimer’s disease (AD). Measurement of Aβ42, t-tau, and p-tau in cerebrospinal fluid (CSF) is the most accepted method to support the diagnosis of AD. However, lumbar puncture represents an invasive investigation, whereas saliva is one of the most accessible body fluids. The aim of our study was to investigate salivary concentrations in AD and evaluate the correlation between salivary and CSF Aβ42 concentrations in AD patients, patients with non-AD dementias, and controls. We recruited 100 subjects: 18 AD patients, 64 patients with non-AD dementias, and 18 controls. The mean saliva Aβ42 concentrations in AD patients were higher than in controls (p < 0.001), and to patients with non-AD dementias (p = 0.001). A significant negative correlation between salivary and CSF Aβ42 concentrations was found in the overall group (r = −0.562, p < 0.001) and in non-AD patients (r = −0.443, p < 0.001). Salivary Aβ42 concentrations positively correlated with CSF t-tau (r = 0.321, p = 0.001) and p-tau (r = 0.297, p = 0.001). Our study showed that in AD patients’ saliva, Aβ42 concentrations are specifically increased, and we found an interesting negative correlation between CSF and salivary Aβ42 concentrations that warrants further investigation.
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- 2022
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34. Protective association of HLA‐DRB1 *04 subtypes in neurodegenerative diseases implicates acetylated tau PHF6 sequences
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Yann Le Guen, Guo Luo, Aditya Ambati, Vincent Damotte, Iris E Jansen, Eric Yu, Aude Nicolas, Itziar de Rojas, Thiago Peixoto Leal, Akinori Miyashita, Céline Bellenguez, Michelle Mulan Lian, Kayenat Parveen, Takashi Morizono, Hyeonseul Park, Benjamin Grenier‐Boley, Tatsuhiko Naito, Fahri Küçükali, Seth D. Talyansky, Selina Marie Yogeshwar, Vicente Sempere, Wataru Satake, Victoria Álvarez‐Martínez, Beatrice Arosio, Michael E Belloy, Luisa Benussi, Anne Boland, Barbara Borroni, María J. Bullido, Paolo Caffarra, Jordi Clarimon, Antonio Daniele, Daniel Darling, Stéphanie Debette, Jean‐François Deleuze, Martin Dichgans, Carole Dufouil, Emmanuel During, Emrah Duzel, Daniela Galimberti, Guillermo García‐Ribas, Jose María García‐Alberca, Pablo García‐González, Vilmantas Giedraitis, Oliver Goldhardt, Caroline Graff, Edna Grunblatt, Olivier Hanon, Lucrezia Hausner, Stefanie Heilmann‐Heimbach, Henne Holstege, Jakub Hort, Yoo Jin Jung, Deckert Jurgen, Silke Kern, Teemu Kuulasmaa, Kun Ho Lee, Ling Ling, Carlo Masullo, Patrizia Mecocci, Shima Mehrabian, Alexandre de Mendonça, Mercè Boada, Pablo Mir, Susanne Moebus, Fermin Moreno, Benedetta Nacmias, Gaël Nicolas, Shumpei Niida, Børge G. Nordestgaard, Goran Papenberg, Janne M. Papma, Lucilla Parnetti, Florence Pasquier, Pau Pastor, Oliver Peters, Yolande A.L. Pijnenburg, Gerard Piñol‐Ripoll, Julius Popp, Laura Molina, Raquel Puerta, Jordi Pérez‐Tur, Innocenzo Rainero, Luis Miguel Real, Steffi G. Riedel‐Heller, Eloy Rodríguez Rodríguez, José Luís Royo, Dan Rujescu, Nikolaos Scarmeas, Philip Scheltens, Norbert Scherbaum, Anja Schneider, Davide Seripa, Ingmar Skoog, Vincenzo Solfrizzi, Gianfranco Spalletta, Alessio Squassina, John C van Swieten, Raquel Sanchez‐Valle, Eng‐King Tan, Thomas Tegos, Charlotte E. Teunissen, Jesper Qvist Thomassen, Lucio Tremolizzo, Martin Vyhnalek, Frans R.J. Verhey, Margda Waern, Jens Wiltfang, Jing Zhang, Henrik Zetterberg, Kaj Blennow, Julie Williams, Philippe Amouyel, Frank Jessen, Patrick G Kehoe, Ole Andreassen, Cornelia M van Duijn, Magda Tsolaki, Pascual Sanchez‐Juan, Ruth Frikke‐Schmidt, Kristel Sleegers, Tatsushi Toda, Anna Zettergren, Martin Ingelsson, Yukinori Okada, Giacomina Rossi, Mikko Hiltunen, Jungsoo Gim, Kouichi Ozaki, Rebecca Sims, Jia Nee Foo, Wiesje M. van der Flier, Takeshi Ikeuchi, Alfredo Ramirez, Ignacio Mata, Agustin Ruiz, Ziv Gan‐Or, Jean‐Charles Lambert, Michael D Greicius, and Emmanuel Mignot
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2022
35. The Carers’ Needs Assessment for Dementia (CNA-D): a validation study in the Italian population
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Andrea Marcinnò, Paola De Martino, Alessandro Vacca, Mario Bo, Milena Zucca, Marcella Maria Caglio, Elisa Rubino, and Innocenzo Rainero
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Italian ,Beck Anxiety Inventory ,CNA-D ,Validity ,Need assessment ,Dermatology ,03 medical and health sciences ,0302 clinical medicine ,Surveys and Questionnaires ,Validation ,medicine ,Humans ,Dementia ,030214 geriatrics ,Family caregivers ,Beck Depression Inventory ,Reproducibility of Results ,General Medicine ,Caregiver ,medicine.disease ,Psychiatry and Mental health ,Distress ,Caregivers ,Scale (social sciences) ,Needs assessment ,Original Article ,Neurology (clinical) ,Psychology ,Needs Assessment ,030217 neurology & neurosurgery ,Clinical psychology - Abstract
Background Dementia has devastating consequences for families with important physical, psychological, social, and financial effects. Evaluation of caregiver’s needs may be an important step to reduce the burden of family caregivers of dementia patients. An Austrian scale, the Carers’ Needs Assessment for Dementia, is now available for measuring the caregiver’s needs. The aim of our study was to evaluate the psychometric properties of the Italian version of the CNA-D (iCNA-D). Methods A sample of 214 voluntary caregivers of dementia patients was recruited at the Department of Neuroscience, University of Turin (Italy). All participants were administered the iCNA-D. Validity and reliability of the instrument were evaluated using Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Symptom Checklist-90 (SCL-90), and the Italian version of Zarit Burden Interview (I-ZBI). Results The most common unmet need reported for the iCNA-D was “counseling and emotional support” (31.5%). This item demonstrates adequate reliability with moderate internal consistency for all “summary scores” of iCNA-D (α ≥ 0.75) and split-half correlation of more than 0.80 for two of them. We also found positive correlations in two out of three “summary scores” of iCNA-D and in the overall outcomes of BDI, BAI, SCL-90, and I-ZBI. Conclusions The iCNA-D could be a valid and reliable tool for a comprehensive assessment of needs and possible social supports proposed to relatives who take care of patients with dementia. Better understanding of family caregivers’ needs could improve planning of local services and reduce caregivers’ perception of distress and burden.
- Published
- 2021
36. Protective association of HLA-DRB1*04 subtypes in neurodegenerative diseases implicates acetylated tau PHF6 sequences
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Emmanuel Mignot, Yann Le Guen, Guo Luo, Aditya Ambati, Vincent Damotte, Iris Jansen, Eric Yu, Aude Nicolas, Itziar de Rojas, Thiago Leal, Akinori Miyashita, Céline Bellenguez, Michelle Lian, Kayenat Parveen, Takashi Morizono, Hyeonseul Park, Benjamin Grenier-Boley, Tatsuhiko Naito, Fahri Küçükali, Seth Talyansky, Selina Yogeshwar, Vicente Sempere, Wataru Sempere, Victoria Álvarez, Beatrice Arosio, Michael Belloy, Luisa Benussi, Anne Boland, Barbara Borroni, Maria Jesus Bullido, Paolo Caffarra, Jordi Clarimon, Antonio DANIELE, Daniel Darling, Stéphanie Debette, Jean-François Deleuze, Martin Dichgans, Carole Dufouil, Emmanuel During, Emrah Düzel, Daniela Galimberti, Guillermo Garcia-Ribas, Jose María García-Alberca, Pablo García-González, Vilmantas Giedraitis, Oliver Goldhardt, Caroline Graff, Edna Grünblatt, Oliver Hanon, Lucrezia Hausner, Stefanie Heilmann-Heimbach, Henne Holstege, Jakub Hort, Yoo Jin Jung, Jürgen Deckert, Silke Kern, Teemu Kuulasmaa, Ling Ling, Carlo Masullo, Patrizia Mecocci, Shima Mehrabian, Alexandre de Mendonça, Merce Boada, Pablo Mir, Susanne Moebus, Fermin Moreno, Benedetta Nacmias, Gaël Nicolas, Shumpei Niida, Børge Nordestgaard, Goran Papenberg, Janne Papma, Lucilla Parnetti, Florence Pasquier, Pau Pastor, Oliver Peters, Yolande Pijnenburg, Gerard Piñol-Ripoll, Julius Popp, Laura Molina-Porcel, Raquel Puerta Fuentes, Jordi Pérez-Tur, Innocenzo Rainero, Inez Ramakers, Luis Real, Steffi Riedel-Heller, Eloy Rodriguez-Rodriguez, Jose Luis Royo, Dan Rujescu, Nikolaos Scarmeas, Philip Scheltens, Norbert Scherbaum, Anja Schneider, Davide Seripa, Ingmar Skoog, Vincenzo Solfrizzi, Gianfranco Spalletta, Alessio Squassina, John van Swieten, Raquel Sánchez-Valle, Eng-King Tan, Thomas Tegos, Charlotte Teunissen, Jesper Qvist Thomassen, Lucio Tremolizzo, Martin Vyhnalek, Frans Verhey, Margda Waern, Jens Wiltfang, Jing Zhang, Henrik Zetterberg, Kaj Blennow, Julie Williams, Philippe Amouyel, Frank Jessen, Patrick Kehoe, Ole Andreassen, Cornelia van Duijn, magda tsolaki, Pascual Sanchez-Juan, Ruth Frikke-Schmidt, Kristel Sleegers, Tatsushi Toda, Anna Zettergren, Martin Ingelsson, Yukinori Okada, Giacomina Rossi, Mikko Hiltunen, Jungsoo Gim, Kouichi Ozaki, Rebecca Sims, Jia Nee Foo, Wiesje van der Flier, Takeshi Ikeuchi, Alfredo Ramirez, Ignacio Mata, Agustín Ruiz, Ziv Gan-Or, Kun Ho Lee, Jean-Charles Lambert, and Michael Greicius
- Abstract
Using genome-wide association data, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s (PD) or Alzheimer’s (AD) disease versus controls across ancestry groups. A shared genetic association was observed across diseases at rs601945 (PD: odds ratio (OR)=0.84; 95% confidence interval, [0.80; 0.88]; p=2.2x10-13; AD: OR=0.91[0.89; 0.93]; p=1.8x10-22), and with a protective HLA association recently reported in amyotrophic lateral sclerosis (ALS). Hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03, and absent for HLA-DRB1*04:05. The same signal was associated with decreased neurofibrillary tangles (but not neuritic plaque density) in postmortem brains and was more strongly associated with tau levels than Aβ42 levels in the cerebrospinal fluid. Finally, protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, but only when acetylated at K311, a modification central to aggregation. An HLA-DRB1*04-mediated adaptive immune response, potentially against tau, decreases PD, AD and ALS risk, offering the possibility of new therapeutic avenues.
- Published
- 2022
37. Brain 18 F-Florbetapir PET/CT Findings in an Early-onset Alzheimer Disease Patient Carrying Presenilin-1 G378E Mutation
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Ugo Paolo Guerra, Innocenzo Rainero, Natale Quartuccio, Daniele Imperiale, Angelina Cistaro, Laura Cassalia, Cristiana Atzori, and D. Vai
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Male ,Adult ,Pathology ,medicine.medical_specialty ,Amyloidogenic Proteins ,Presenilin ,Alzheimer Disease ,Fluorodeoxyglucose F18 ,Positron Emission Tomography Computed Tomography ,mental disorders ,PSEN2 ,Presenilin-2 ,medicine ,PSEN1 ,Humans ,familial Alzheimer disease ,Cerebral atrophy ,presenilin-1 ,PET-CT ,PET ,MRI ,florbetapir ,APP ,Amyloid beta-Peptides ,medicine.diagnostic_test ,business.industry ,Brain ,Magnetic resonance imaging ,medicine.disease ,Psychiatry and Mental health ,Clinical Psychology ,Positron emission tomography ,Positron-Emission Tomography ,Mutation ,Geriatrics and Gerontology ,Alzheimer's disease ,business ,Gerontology - Abstract
Positron emission tomography (PET) with 18 F-Fluorodeoxyglucose ( 18 F-FDG) plays an outstanding role in the diagnostic work-up of dementia. Amyloid PET imaging is a complementary imaging technique for the early detection of Alzheimer disease (AD). β-amyloid precursor protein ( APP ), Presenilin-1 ( PSEN1 ) and Presenilin-2 ( PSEN2 ) are the 3 main causative genes responsible for autosomal dominant early-onset Alzheimer disease (EOAD). This is the first report of 18 F-Florbetapir amyloid imaging findings in a 35-year-old male patient with EOAD carrying the G378E mutation in PSEN1 gene. Brain computed tomography (CT) and magnetic resonance imaging scans showed remarkable cerebral atrophy with dilatation of the cerebrospinal fluid spaces; furthermore, a 18 F-Florbetapir PET/CT scan demonstrated also widespread remarkable accumulation of the amyloid tracer in the cerebral cortex, with reduction of the normal contrast between white and gray matter and flattening of the external cortical margins. Furthermore, PET/CT showed intense 18 F-florbetapir uptake in the striatum and in the thalamus bilaterally. Our case supports the usefulness of amyloid PET imaging in the diagnostic work-up of EOAD.
- Published
- 2022
38. Cochlear Implant Results in Older Adults with Post-Lingual Deafness: The Role of 'Top-Down' Neurocognitive Mechanisms
- Author
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Milena Zucca, Andrea Albera, Roberto Albera, Carla Montuschi, Beatrice Della Gatta, Andrea Canale, and Innocenzo Rainero
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cochlear implant ,hearing impairment ,neurocognition ,older adults ,processing speed ,speech recognition ,Health, Toxicology and Mutagenesis ,Public Health, Environmental and Occupational Health ,Deafness ,Cochlear Implantation ,Cochlear Implants ,Treatment Outcome ,Speech Perception ,otorhinolaryngologic diseases ,Medicine ,Humans ,Prospective Studies ,Aged - Abstract
To date, no clear specific cognitive predictors of speech perception outcome in older adult cochlear implant (CI) users have yet emerged. The aim of this prospective study was to increase knowledge on cognitive and clinical predictors of the audiological outcome in adult cochlear implant users. A total of 21 patients with post-lingual deafness, who were candidates for cochlear implantation, were recruited at the Department of Ear, Nose and Throat, University of Torino (Italy) and subjected to a pre-operatory neuropsychological assessment (T0) and an audiological examination after 12 months of implantation (T12). Patients who, at T12, had a 60 dB verbal recognition above 80%, were younger (z = −2.131, p = 0.033) and performed better in the Verbal Semantic Fluency Test at T0 (z = −1.941, p = 0.052) than subjects who had a 60 dB verbal recognition at T12 below 80%. The most significant predictors of the CI audiological outcome at T12 were age (β = −0.492, p = 0.024) and patients’ TMT-A performance at baseline (β = −0.486, p = 0.035). We conclude that cognitive processing speed might be a good predictor of the level of speech understanding in older adult patients with CI after one year of implantation.
- Published
- 2022
39. Rare missense variant (R251G) on APOE counterbalances the Alzheimer’s disease risk associated with APOE‐ε4
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Yann Le Guen, Michael E Belloy, Benjamin Grenier‐Boley, Itziar de Rojas, Atahualpa Castillo, Iris E Jansen, Aude Nicolas, Céline Bellenguez, Carolina Dalmasso, Fahri Küçükali, Sarah J Eger, Victoria Álvarez‐Martínez, Beatrice Arosio, Luisa Benussi, Anne Boland, Barbara Borroni, María J. Bullido, Paolo Caffarra, Jordi Clarimón, Delphine Daian, Antonio Daniele, Stéphanie Debette, Jean‐François Deleuze, Martin Dichgans, Carole Dufouil, Emrah Duzel, Daniela Galimberti, Jose María García‐Alberca, Pablo García‐González, Vilmantas Giedraitis, Timo Grimmer, Caroline Graff, Edna Grunblatt, Olivier Hanon, Lucrezia Hausner, Stefanie Heilmann‐Heimbach, Henne Holstege, Jakub Hort, Deckert Jurgen, Teemu Kuulasmaa, Aad van der Lugt, Carlo Masullo, Patrizia Mecocci, Shima Mehrabian, Alexandre de Mendonça, Mercè Boada, Pablo Mir, Susanne Moebus, Fermin Moreno, Benedetta Nacmias, Gaël Nicolas, Goran Papenberg, Lucilla Parnetti, Florence Pasquier, Pau Pastor, Oliver Peters, Yolande A.L. Pijnenburg, Gerard Piñol‐Ripoll, Julius Popp, Laura Molina, Raquel Puerta, Jordi Pérez‐Tur, Innocenzo Rainero, Inez H.G.B. Ramakers, Katrine Laura Rasmussen, Luis Miguel Real, Steffi G. Riedel‐Heller, Eloy Rodríguez Rodríguez, José Luís Royo, Dan Rujescu, Nikolaos Scarmeas, Philip Scheltens, Norbert Scherbaum, Anja Schneider, Davide Seripa, Hilkka Soininen, Vincenzo Solfrizzi, Gianfranco Spalletta, Alessio Squassina, John C van Swieten, Raquel Sanchez‐Valle, Thomas Tegos, Jesper Qvist Thomassen, Lucio Tremolizzo, Frans R.J. Verhey, Martin Vyhnalek, Jens Wiltfang, Zihuai He, Valerio Napolioni, Philippe Amouyel, Frank Jessen, Patrick G Kehoe, Cornelia M van Duijn, Magda Tsolaki, Pascual Sanchez‐Juan, Kristel Sleegers, Martin Ingelsson, Giacomina Rossi, Mikko Hiltunen, Rebecca Sims, Wiesje M. van der Flier, Alfredo Ramirez, Ole Andreassen, Ruth Frikke‐Schmidt, Julie Williams, Agustin Ruiz, Jean‐Charles Lambert, and Michael D Greicius
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2022
40. Synaptic Proteins as Fluid Biomarkers in Alzheimer's Disease: A Systematic Review and Meta-Analysis
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Fausto Roveta, Aurora Cermelli, Silvia Boschi, Fabio Ferrandes, Alberto Grassini, Andrea Marcinnò, Margherita Spina, Elisa Rubino, Tiziana Borsello, Alessandro Vercelli, and Innocenzo Rainero
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neurogranin ,Settore BIO/16 - Anatomia Umana ,synaptic dysfunction ,General Neuroscience ,GAP-43 ,synaptotagmin-1 ,General Medicine ,cerebrospinal fluid ,meta-analysis ,Psychiatry and Mental health ,Clinical Psychology ,systematic review ,blood ,Alzheimer’s disease ,SNAP-25 ,Geriatrics and Gerontology - Abstract
Background: Synaptic disruption precedes neuronal death and correlates with clinical features of Alzheimer’s disease (AD). The identification of fluid biomarkers of synaptic damage is emerging as a goal for early and accurate diagnosis of the disease. Objective: To perform a systematic review and meta-analysis to determine whether fluid biomarkers of synaptic damage are impaired in AD. Methods: PubMed, Scopus, EMBASE, and Web of Science were searched for articles reporting synaptic proteins as fluid biomarkers in AD and cognitively unimpaired (CU) individuals. Pooled effect sizes were determined using the Hedge G method with random effects. Questions adapted from the Quality Assessment of Diagnostic Accuracy Studies were applied for quality assessment. A protocol for this study has been previously registered in PROSPERO (registration number: CRD42021277487). Results: The search strategy identified 204 articles that were assessed for eligibility. A total of 23 studies were included in the systematic review and 15 were included in the meta-analysis. For Neurogranin, 827 AD and 1,237 CU subjects were included in the meta-analysis, showing a significant increase in cerebrospinal fluid of patients with AD compared to CU individuals, with an effect size of 1.01 (p
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- 2022
41. Anxiety and depression in Alzheimer's disease: a systematic review of pathogenetic mechanisms and relation to cognitive decline
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Rossana Botto, Nicoletta Callai, Aurora Cermelli, Lorenzo Causarano, and Innocenzo Rainero
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Depression ,Dermatology ,General Medicine ,Anxiety ,Anxiety Disorders ,Receptors, N-Methyl-D-Aspartate ,Alzheimer’s disease ,Dementia ,Psychological symptoms ,Psychiatry and Mental health ,Alzheimer Disease ,Humans ,Cognitive Dysfunction ,Neurology (clinical) ,Biomarkers - Abstract
Objectives To explore the pathogenetic hypothesis provided to explain the comorbidity of anxious and depressive symptomatology and AD and to assess the association between anxious and depressive symptoms and the AD-related cognitive impairment. Methods In October 2020 and March 2021, PsycINFO, Embase, Ovid, and CINAHL were searched for peer-reviewed original articles investigating anxiety and/or depression in AD. Results A total of 14,760 studies were identified and 34 papers on AD patients were included in the review. Suggested biological causes of depression and anxiety in AD include higher strychnine-sensitive glycine receptor (GlyRS) functioning and selective reduction of N-methyl-d-aspartate (NMDA) receptor NR2A density, cortical and limbic atrophy, lower resting cortical metabolism, lower CSF Aβ42 and higher t-tau and p-tau levels, and neuritic plaques. At the same time, dysthymia arises in the early stages of AD as an emotional reaction to the progressive cognitive decline and can cause it; anxiety can appear as an initial compensating behaviour; and depression might be related to AD awareness and loss of functional abilities. Affective symptoms and the expression of the depressive symptoms tend to reduce as AD progresses. Conclusion The neurodegeneration of areas and circuits dealing with emotions can elicit anxiety and depression in AD. In the early stages of the disease, anxiety and depression could arise as a psychological reaction to AD and due to coping difficulties. In late AD stages, the cognitive impairment reduces the emotional responses and their expression. Anxiety and depression are more intense in early-onset AD, due to the major impact of AD on the individual.
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- 2022
42. Impact of COVID-19 on chronic migraine treated with erenumab: a case report
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Elisa Rubino, Silvia Boschi, Innocenzo Rainero, Aurora Cermelli, Andrea Marcinnò, Fausto Roveta, Alberto Grassini, and Erica Gallo
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medicine.medical_specialty ,Neurology ,Migraine Disorders ,Dermatology ,Calcitonin gene-related peptide ,Antibodies, Monoclonal, Humanized ,Antibodies ,03 medical and health sciences ,0302 clinical medicine ,Chronic Migraine ,Calcitonin Gene-Related Peptide Receptor Antagonists ,Hyposmia ,Internal medicine ,Monoclonal ,medicine ,Humans ,Viral ,CGRP ,030212 general & internal medicine ,Humanized ,Chronic migraine ,COVID-19 ,Erenumab ,SARS-Cov-2 ,Middle Aged ,RNA, Viral ,SARS-CoV-2 ,business.industry ,Trigeminovascular system ,General Medicine ,medicine.disease ,Psychiatry and Mental health ,Migraine ,RNA ,Neurology (clinical) ,Neurosurgery ,Headaches ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Background Headache is a frequent symptom of the novel coronavirus 19 disease (COVID-19). To date, there are limited information on how COVID-19 affects migraine and its treatment. Case description A 47-year-old patient, suffering from chronic migraine and medication-overuse headache, in September 2020 started erenumab at 70 mg once monthly. Two months later, monthly migraine days decreased from 20 to 5. On the third month, the patient developed mild COVID-19 symptoms, experiencing extreme fatigue, hyposmia, and attention deficit, resulting positive for SARS-Cov-2 RNA. A significant increase in migraine attacks frequency was reported. Brain MRI and EEG were normal. Erenumab was increased to 140 mg/month, and attacks decreased to 3 monthly migraine days and remained stable. All the headaches experienced by our patient during the infection fulfilled the criteria of the migraine attacks, without tensive-like features. Conclusion We report the first case showing the effects of SARS-CoV-2 infection in a patient with chronic migraine and medication-overuse headache treated with erenumab. Our case description suggests that inflammatory processes induced by SARS-CoV-2 infection may increase the frequency of migraine attacks, probably through an activation of the trigeminovascular system. Whether treatment with CGRP receptor antagonist may influence COVID is still debated. Additional studies regarding anti-CGRP monoclonal antibodies in COVID-19 patients are warranted.
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- 2021
43. Migraine pathways and the identification of novel therapeutic targets
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Cecilia Noviello, Alessandro Vacca, Innocenzo Rainero, Elisa Rubino, and Fausto Roveta
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TRPM8 ,0301 basic medicine ,Migraine Disorders ,Clinical Biochemistry ,Circadian clock ,Hypothalamus ,Pain ,Disease ,circadian clocks ,Ion Channels ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,aura ,PACAP1-38 ,Drug Discovery ,Animals ,Humans ,Medicine ,Molecular Targeted Therapy ,Migraine ,Pharmacology ,Metal ion homeostasis ,business.industry ,metal ion homeostasis ,glucose metabolism ,therapeutic target ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cortical spreading depression ,hypothalamus ,ion channels ,Synaptic plasticity ,Molecular Medicine ,Neurovascular Disorder ,business ,Neuroscience - Abstract
Introduction: Migraine is a chronic neurovascular disorder characterized by recurrent headache attacks associated with neurological and autonomic symptoms. The pathophysiological mechanisms of the disease are extremely complex, involving hypothalamic and trigeminovascular activation, cortical spreading depression, release of pro-inflammatory peptides, peripheral and central sensitization. The underlying cellular and molecular mechanisms have been scarcely investigated. Recently, genetic studies have suggested that different metabolic pathways could be involved in the pathogenesis of migraine.Areas covered: This review focuses on cellular and molecular mechanisms involved in migraine, suggesting a role for circadian clocks, ion channels, synaptic plasticity, vascular factors, ion metal homeostasis, and impaired glucose metabolism in the pathogenesis of the disease. Accordingly, the article proposes new therapeutic targets that may be of particular relevance for disease prevention.Expert opinion: Several complex molecular mechanisms are involved in setting the genetic threshold for migraine and the pathogenesis of headache attacks. Most promising new therapeutic targets are the modulation of hypothalamic activity and ion channels involved in pain transmission. Further studies in animals and humans are necessary to enhance the elucidation of the molecular mechanisms of migraine and open new avenues for disease prevention.
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- 2020
44. Migraine, Brain Glucose Metabolism and the 'Neuroenergetic' Hypothesis: A Scoping Review
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Lorenzo Del Moro, Eugenia Rota, Elenamaria Pirovano, and Innocenzo Rainero
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Migraine Disorders ,brain insulin resistance ,Brain ,glucose ,insulin sensitivity ,migraine ,postprandial hypoglycemia ,Anesthesiology and Pain Medicine ,Glucose ,Neurology ,Humans ,Insulin ,Neurology (clinical) ,Insulin Resistance - Abstract
Increasing evidence suggests that migraine may be the result of an impaired brain glucose metabolism. Several studies have reported brain mitochondrial dysfunction, impaired brain glucose metabolism and gray matter volume reduction in specific brain areas of migraineurs. Furthermore, peripheral insulin resistance, a condition demonstrated in several studies, may extend to the brain, leading to brain insulin resistance. This condition has been proven to downregulate insulin receptors, both in astrocytes and neurons, triggering a reduction in glucose uptake and glycogen synthesis, mainly during high metabolic demand. This scoping review examines the clinical, epidemiologic and pathophysiologic data supporting the hypothesis that abnormalities in brain glucose metabolism may generate a mismatch between the brain's energy reserve and metabolic expenditure, triggering migraine attacks. Moreover, alteration in glucose homeostasis could generate a chronic brain energy deficit promoting migraine chronification. Lastly, insulin resistance may link migraine with its comorbidities, like obesity, depression, cognitive impairment and cerebrovascular diseases. PERSPECTIVE: Although additional experimental studies are needed to support this novel "neuroenergetic" hypothesis, brain insulin resistance in migraineurs may unravel the pathophysiological mechanisms of the disease, explaining the migraine chronification and connecting migraine with comorbidities. Therefore, this hypothesis could elucidate novel potential approaches for migraine treatment.
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- 2021
45. Increased orexin A concentrations in cerebrospinal fluid of patients with behavioural variant frontotemporal dementia
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Fausto Roveta, Stefania Cattaldo, Erica Gallo, Lorenzo Priano, Riccardo Cremascoli, Alessandro Mauro, Elisa Rubino, Silvia Boschi, Innocenzo Rainero, and Andrea Marcinnò
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0301 basic medicine ,medicine.medical_specialty ,Neurology ,media_common.quotation_subject ,Dermatology ,Arousal ,03 medical and health sciences ,Orexin-A ,0302 clinical medicine ,Cerebrospinal fluid ,Sleep and metabolism ,Internal medicine ,mental disorders ,medicine ,Hypocretin-1 ,Humans ,Frontotemporal dementia ,Orexin A ,media_common ,Orexins ,business.industry ,Appetite ,General Medicine ,medicine.disease ,Psychiatry and Mental health ,030104 developmental biology ,Endocrinology ,nervous system ,Case-Control Studies ,Frontotemporal Dementia ,Anxiety ,Original Article ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Orexins are hypothalamic neuropeptides that regulate several physiological functions, such as appetite, arousal, cognition, stress, sleep and metabolism. Emerging pieces of evidence suggest an orexinergic dysfunction in several neuropsychiatric disorders, including depression, anxiety and addiction. A syndromic overlap between behavioural variant frontotemporal dementia (bvFTD) and several psychiatric disorders was recently demonstrated. Therefore, we analysed cerebrospinal fluid (CSF) orexin A concentrations of 40 bvFTD and 32 non-demented patients, correlating neuropeptide concentrations with several clinical characteristics. A significant increase of orexin A concentrations was found in bvFTD patients when compared to controls (p
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- 2021
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46. A novel neurocognitive approach for placebo analgesia in neurocognitive disorders
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Paolo Fonio, Elisa Rubino, Sara Palermo, Francesco Sardanelli, Federico D'Agata, Martina Amanzio, Innocenzo Rainero, Lene Vase, and Mario Stanziano
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Male ,0301 basic medicine ,Aging ,Neuropsychological Tests ,Audiology ,Biochemistry ,Executive functions ,Executive Function ,0302 clinical medicine ,Endocrinology ,Placebo analgesia ,Medicine ,Gray Matter ,Prefrontal cortex ,medicine.diagnostic_test ,fMRI ,Neuropsychology ,Pain Perception ,Cognition ,Middle Aged ,Magnetic Resonance Imaging ,medicine.anatomical_structure ,Response inhibition ,Female ,medicine.medical_specialty ,Neurocognitive Disorders ,Prefrontal Cortex ,Grey matter ,behavioral disciplines and activities ,Anterior cingulate cortex ,Neurocognitive disorders ,03 medical and health sciences ,Atrophy ,Alzheimer Disease ,Genetics ,Humans ,Molecular Biology ,Aged ,Neural correlates of consciousness ,business.industry ,Cell Biology ,Placebo Effect ,medicine.disease ,030104 developmental biology ,nervous system ,Analgesia ,business ,Functional magnetic resonance imaging ,Neurocognitive ,030217 neurology & neurosurgery - Abstract
Neural correlates of placebo analgesia (PA) in patients with neurocognitive disorders have not yet been elucidated. The present study aimed to evaluate how and to what extent executive (dys)functions of the medial prefrontal cortex (MPFC) may be related to PA. To this end, twenty-three subjects complaining of different cognitive deficits (from mild cognitive impairment likely due to Alzheimer's disease to mild AD) were recruited. PA was investigated by a well-known experimental venipuncture pain paradigm (open versus hidden [O-H] application of lidocaine). Patients also underwent a comprehensive neuropsychological evaluation and a functional magnetic resonance imaging (fMRI) GO/No-GO task for eliciting selective activation of the MPFC. Selected neuropsychological variables were correlated to the OH-PA paradigm. The association between the fMRI response on the “No-GO” versus “GO” contrast and PA was investigated over the whole-brain by regression analysis. We showed the existence of a relationship between a lower PA and MPFC dysfunctions through the neuropsychological and fMRI assessment. A separate voxel-based morphometry (VBM) analysis controlled for possible influence of grey matter (GM) volume reduction on both fMRI results and PA. fMRI results were not directly affected by, and therefore independent of, disease-specific GM atrophy, which was indeed located more anteriorly within the rostral anterior cingulate and inversely correlated with PA. Our findings shed new light on the underestimated contribution of executive (dys)functions mediated by the MPFC (response-inhibition, self-monitoring and set-shifting abilities) in PA pathogenesis, with a special purely (i.e. independently from brain structural alterations) functional role played by the MCC. Results are discussed in terms of possible clinical relevance in the management of patients with neurocognitive disorders.
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- 2019
47. Gene Expression Imputation Across Multiple Tissue Types Provides Insight Into the Genetic Architecture of Frontotemporal Dementia and Its Clinical Subtypes
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Lianne M. Reus, Bogdan Pasaniuc, Danielle Posthuma, Toni Boltz, Yolande A.L. Pijnenburg, Roel A. Ophoff, Raffaele Ferrari, Dena G. Hernandez, Michael A. Nalls, Jonathan D. Rohrer, Adaikalavan Ramasamy, John B.J. Kwok, Carol Dobson-Stone, William S. Brooks, Peter R. Schofield, Glenda M. Halliday, John R. Hodges, Olivier Piguet, Lauren Bartley, Elizabeth Thompson, Isabel Hernández, Agustín Ruiz, Mercè Boada, Barbara Borroni, Alessandro Padovani, Carlos Cruchaga, Nigel J. Cairns, Luisa Benussi, Giuliano Binetti, Roberta Ghidoni, Gianluigi Forloni, Daniela Galimberti, Chiara Fenoglio, Maria Serpente, Elio Scarpini, Jordi Clarimón, Alberto Lleó, Rafael Blesa, Maria Landqvist Waldö, Karin Nilsson, Christer Nilsson, Ian R.A. Mackenzie, Ging-Yuek R. Hsiung, David M.A. Mann, Jordan Grafman, Christopher M. Morris, Johannes Attems, Timothy D. Griffiths, Ian G. McKeith, Alan J. Thomas, Pietro Pietrini, Edward D. Huey, Eric M. Wassermann, Atik Baborie, Evelyn Jaros, Michael C. Tierney, Pau Pastor, Cristina Razquin, Sara Ortega-Cubero, Elena Alonso, Robert Perneczky, Janine Diehl-Schmid, Panagiotis Alexopoulos, Alexander Kurz, Innocenzo Rainero, Elisa Rubino, Lorenzo Pinessi, Ekaterina Rogaeva, Peter St. George-Hyslop, Giacomina Rossi, Fabrizio Tagliavini, Giorgio Giaccone, James B. Rowe, Johannes C.M. Schlachetzki, James Uphill, John Collinge, Simon Mead, Adrian Danek, Vivianna M. Van Deerlin, Murray Grossman, John Q. Trojanowski, Julie van der Zee, Christine Van Broeckhoven, Stefano F. Cappa, Isabelle Le Ber, Didier Hannequin, Véronique Golfier, Martine Vercelletto, Alexis Brice, Benedetta Nacmias, Sandro Sorbi, Silvia Bagnoli, Irene Piaceri, Jørgen E. Nielsen, Lena E. Hjermind, Matthias Riemenschneider, Manuel Mayhaus, Bernd Ibach, Gilles Gasparoni, Sabrina Pichler, Wei Gu, Martin N. Rossor, Nick C. Fox, Jason D. Warren, Maria Grazia Spillantini, Huw R. Morris, Patrizia Rizzu, Peter Heutink, Julie S. Snowden, Sara Rollinson, Anna Richardson, Alexander Gerhard, Amalia C. Bruni, Raffaele Maletta, Francesca Frangipane, Chiara Cupidi, Livia Bernardi, Maria Anfossi, Maura Gallo, Maria Elena Conidi, Nicoletta Smirne, Rosa Rademakers, Matt Baker, Dennis W. Dickson, Neill R. Graff-Radford, Ronald C. Petersen, David Knopman, Keith A. Josephs, Bradley F. Boeve, Joseph E. Parisi, William W. Seeley, Bruce L. Miller, Anna M. Karydas, Howard Rosen, John C. van Swieten, Elise G.P. Dopper, Harro Seelaar, Philip Scheltens, Giancarlo Logroscino, Rosa Capozzo, Valeria Novelli, Annibale A. Puca, Massimo Franceschi, Alfredo Postiglione, Graziella Milan, Paolo Sorrentino, Mark Kristiansen, Huei-Hsin Chiang, Caroline Graff, Florence Pasquier, Adeline Rollin, Vincent Deramecourt, Florence Lebert, Dimitrios Kapogiannis, Luigi Ferrucci, Stuart Pickering-Brown, Andrew B. Singleton, John Hardy, Parastoo Momeni, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Child and Adolescent Psychiatry / Psychology, Erasmus MC other, Neurology, Psychiatry, Human genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Reproduction & Development (AR&D), and Amsterdam Neuroscience - Neurodegeneration
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0301 basic medicine ,Candidate gene ,17q21.31 inversion region ,Dorsolateral prefrontal cortex ,Expression quantitative trait loci (eQTL) ,Frontotemporal dementia ,SEC22B ,Transcriptome-wide association study ,Semantic dementia ,Gene Expression ,Locus (genetics) ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Progressive nonfluent aphasia ,mental disorders ,medicine ,Humans ,Gene ,Biological Psychiatry ,Genetics ,nutritional and metabolic diseases ,medicine.disease ,Genetic architecture ,nervous system diseases ,030104 developmental biology ,medicine.anatomical_structure ,Frontotemporal Dementia ,030217 neurology & neurosurgery - Abstract
Background: The etiology of frontotemporal dementia (FTD) is poorly understood. To identify genes with predicted expression levels associated with FTD, we integrated summary statistics with external reference gene expression data using a transcriptome-wide association study approach. Methods: FUSION software was used to leverage FTD summary statistics (all FTD: n = 2154 cases, n = 4308 controls; behavioral variant FTD: n = 1337 cases, n = 2754 controls; semantic dementia: n = 308 cases, n = 616 controls; progressive nonfluent aphasia: n = 269 cases, n = 538 controls; FTD with motor neuron disease: n = 200 cases, n = 400 controls) from the International FTD-Genomics Consortium with 53 expression quantitative loci tissue type panels (n = 12,205; 5 consortia). Significance was assessed using a 5% false discovery rate threshold. Results: We identified 73 significant gene–tissue associations for FTD, representing 44 unique genes in 34 tissue types. Most significant findings were derived from dorsolateral prefrontal cortex splicing data (n = 19 genes, 26%). The 17q21.31 inversion locus contained 23 significant associations, representing 6 unique genes. Other top hits included SEC22B (a gene involved in vesicle trafficking), TRGV5, and ZNF302. A single gene finding (RAB38) was observed for behavioral variant FTD. For other clinical subtypes, no significant associations were observed. Conclusions: We identified novel candidate genes (e.g., SEC22B) and previously reported risk regions (e.g., 17q21.31) for FTD. Most significant associations were observed in dorsolateral prefrontal cortex splicing data despite the modest sample size of this reference panel. This suggests that our findings are specific to FTD and are likely to be biologically relevant highlights of genes at different FTD risk loci that are contributing to the disease pathology.
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- 2021
48. Investigating the Effects of COVID-19 Quarantine in Migraine: An Observational Cross-Sectional Study From the Italian National Headache Registry (RICe)
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Maria Elena Roca, Francesco De Cesaris, Francesca Pistoia, Andrea Marcinnò, Alessia Putortì, Fausto Roveta, Ilaria Frattale, Valeria Caponnetto, Elena Guaschino, Marianna Delussi, Raffaele Ornello, Pierangelo Geppetti, Gianluca Coppola, Marina de Tommaso, Maria Trojano, Innocenzo Rainero, Grazia Sances, Chiara Abagnale, Simona Sacco, Eleonora Gentile, A. M. P. Prudenzano, Chiara Lupi, and Francesco Pierelli
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Pediatrics ,medicine.medical_specialty ,Cross-sectional study ,Aura ,disgust ,lcsh:RC346-429 ,law.invention ,lockdown ,03 medical and health sciences ,0302 clinical medicine ,Chronic Migraine ,law ,Quarantine ,medicine ,migraine ,030212 general & internal medicine ,resilience ,lcsh:Neurology. Diseases of the nervous system ,Original Research ,business.industry ,COVID-19 ,medicine.disease ,Migraine with aura ,Distress ,Neurology ,Migraine ,Observational study ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Background: Previous studies during SARS and Ebola pandemics have shown that quarantine is associated with several negative psychological effects, such as post-traumatic stress symptoms, confusion, and anger. These conditions may affect the course of many diseases, including migraine. Although it is possible that the quarantine measures for the current COVID-19 pandemic affect migraine burden, no information is currently available on this issue. Aim: In this study, we aimed to: (1) explore the possible changes in migraine frequency, severity, and days with acute medication intake during quarantine period; (2) evaluate possible differences in migraine outcomes in consideration of lifestyle changes, emotions, pandemic diffusion, and COVID-19 infection. Methods: We interviewed patients who were included in the observational Italian Headache Registry (Registro Italiano Cefalee, RICE), retrospectively collecting information on main headache features, lifestyle factors, emotions, individual infection status, and perception of COVID-19 for 2 months before (pre-quarantine) and after the beginning of the quarantine (quarantine). Inclusion criteria were: age > 18, diagnosis of migraine without aura, migraine with aura and chronic migraine, last in-person visit more than 3 months preceding the beginning of quarantine. Results: A total of 433 migraine subjects agreed to be interviewed. We found an overall reduction in headache frequency (9.42 ± 0.43 days with headache vs. 8.28 ± 0.41) and intensity (6.57 ± 0.19 vs. 6.59 ± 0.21) during the quarantine, compared to pre-quarantine. There was a correlation between improvement and number of days of stay-at-home. When results were stratified for geographic area, we found a tendency toward worsening of headache frequency in northern Italy. Disgust regarding viral infection corresponded to a minor improvement in migraine. Conclusions: Migraine patients showed a mild improvement of migraine features, probably attributable to resilient behavior toward pandemic distress. Disgust regarding the contagion whereas potentially favoring defensive behavior, could potentially worsen migraine. The spontaneous limitation of migraine burden during quarantine could favor patient follow-up via the use of telemedicine visits, reliable diaries, and frequent remote contacts.
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- 2020
49. Machine Learning Profiling of Alzheimer's Disease Patients Based on Current Cerebrospinal Fluid Markers and Iron Content in Biofluids
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Antonio Indaco, Silvia Boschi, Innocenzo Rainero, Giuseppe Di Fede, Caterina Guiot, Ornella Abollino, Shoeb Ansari, Federico D'Agata, Paola Caroppo, and Eleonora Ficiarà
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0301 basic medicine ,Aging ,biomarker (BM) ,Cognitive Neuroscience ,Tau protein ,Disease ,Alzheimer's disease ,cerebrospinal fluid ,iron ,mild cognitive impairment ,Machine learning ,computer.software_genre ,lcsh:RC321-571 ,03 medical and health sciences ,0302 clinical medicine ,Cerebrospinal fluid ,Medicine ,Dementia ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Pathological ,Original Research ,biology ,business.industry ,Neurodegeneration ,medicine.disease ,030104 developmental biology ,Etiology ,biology.protein ,Artificial intelligence ,business ,computer ,030217 neurology & neurosurgery ,Frontotemporal dementia ,Neuroscience - Abstract
Alzheimer's disease (AD) is the most common form of dementia, characterized by a complex etiology that makes therapeutic strategies still not effective. A true understanding of key pathological mechanisms and new biomarkers are needed, to identify alternative disease-modifying therapies counteracting the disease progression. Iron is an essential element for brain metabolism and its imbalance is implicated in neurodegeneration, due to its potential neurotoxic effect. However, the role of iron in different stages of dementia is not clearly established. This study aimed to investigate the potential impact of iron both in cerebrospinal fluid (CSF) and in serum to improve early diagnosis and the related therapeutic possibility. In addition to standard clinical method to detect iron in serum, a precise quantification of total iron in CSF was performed using graphite-furnace atomic absorption spectrometry in patients affected by AD, mild cognitive impairment, frontotemporal dementia, and non-demented neurological controls. The application of machine learning techniques, such as clustering analysis and multiclassification algorithms, showed a new potential stratification of patients exploiting iron-related data. The results support the involvement of iron dysregulation and its potential interaction with biomarkers (Tau protein and Amyloid-beta) in the pathophysiology and progression of dementia.
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- 2020
50. The My Active and Healthy Aging ICT platform prevents quality of life decline in older adults: a randomised controlled study
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Mathew J. Summers, Innocenzo Rainero, Marco Bazzani, Dalila Burin, Alessandro Vercelli, Paolo Provero, Michaela Mönter, Eleftheria Giannouli, and Georg Aumayr
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Gerontology ,Prefrail subjects ,Aging ,Randomization ,Frailty ,ICT platform ,Older people ,Quality of life ,RCT ,Psychological intervention ,Nutritional Status ,law.invention ,Healthy Aging ,03 medical and health sciences ,0302 clinical medicine ,Quality of life (healthcare) ,Randomized controlled trial ,law ,Intervention (counseling) ,Medicine ,Humans ,030212 general & internal medicine ,Healthy aging ,Aged ,business.industry ,Cognition ,General Medicine ,Mood ,Research Design ,Quality of Life ,Geriatrics and Gerontology ,business ,030217 neurology & neurosurgery - Abstract
Introduction Prevention of frailty is paramount in older adults. We evaluated the efficacy of a tailored multidomain intervention, monitored with the My Active and Healthy Aging platform, in reducing conversion from a prefrail status to overt frailty and preventing decline in quality of life. Methods We performed a multicentre, multicultural, randomised control study. The effects of multidomain interventions on frailty parameters, quality of life, physical, cognitive, psychosocial function, nutrition and sleep were evaluated in a group of 101 prefrail older subjects and compared with 100 prefrail controls, receiving general health advice. Results At the 12-month assessment, controls showed a decline in quality of life that was absent in the active group. In addition, active participants showed an increase in mood and nutrition function. No effect on remaining parameter was observed. Discussion Our study supports the use of personalised multidomain intervention, monitored with an information and communication technology platform, in preventing quality of life decline in older adults.
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- 2020
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