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1. Cognitive Profile and Its Evolution in a Cohort of Multiple System Atrophy Patients

Author

Luisa Sambati, Giovanna Calandra-Buonaura, Giulia Giannini, Ilaria Cani, Federica Provini, Roberto Poda, Federico Oppi, Michelangelo Stanzani Maserati, and Pietro Cortelli

Subjects
mild cognitive impairment, multiple system atrophy (MSA), cognition, neuropsychology, dementia, Neurology. Diseases of the nervous system, RC346-429
Abstract

Introduction: Cognitive decline is not a characteristic feature of multiple system atrophy (MSA), but recent evidence suggests cognitive impairment as an integral part of the disease. We aim to describe the cognitive profile and its progression in a cohort of patients with MSA.Methods: We retrospectively selected patients referred to our department with a clinical diagnosis of MSA who were evaluated at least once a year during the course of the disease and underwent a comprehensive neuropsychological evaluation.Results: At the first evaluation (T0), 37 out of 60 patients (62%) were cognitively impaired, mainly (76%) in attention and executive functioning. Thirteen patients were impaired in one cognitive domain and 24 in more than one cognitive domain. Six out of the 24 had dementia. Twenty patients underwent a follow-up evaluation (T1) after a mean of 16.6 ± 9.3 months from the first evaluation (T0). Eight out of 20 patients were cognitively normal at both T0 and T1. Seven out of 12 patients presented with stable cognitive impairment at T1, while cognitive decline progressed in five patients. Patients with progression in cognitive decline performed significantly worse at T0 than cognitively stable patients. Education was significantly different between patients with and without cognitive impairment. No other differences in demographic and clinical variables and autonomic or sleep disturbances were found. Patients with dementia were older at disease onset and at T0 and had lower education and disease duration at T0 compared to those in other groups.Conclusions: In patients with MSA, we observed three different cognitive profiles: normal cognition, stable selective attention-executive deficits, and progressive cognitive deficits evolving to dementia. The detection of cognitive impairment in patients with suspected MSA suggests the need for comprehensive and longitudinal neuropsychological evaluation.

Published
2020
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2. Color Choice Preference in Cognitively Impaired Patients: A Look Inside Alzheimer’s Disease Through the Use of Lüscher Color Diagnostic

Author

Michelangelo Stanzani Maserati, Micaela Mitolo, Federica Medici, Renato D’Onofrio, Federico Oppi, Roberto Poda, Maddalena De Matteis, Caterina Tonon, Raffaele Lodi, Rocco Liguori, and Sabina Capellari

Subjects
Alzheimer’s disease, dementia, mild cognitive impairment, color preference, Lüscher color test, personality, Psychology, BF1-990
Abstract

ObjectiveTo study the emotional state of cognitively impaired patients through the color choice preference in a group of Alzheimer’s disease (AD) patients and compare it with a group of Mild Cognitive Impairment (MCI) patients and a matched control group.MethodsA total of 71 AD, 50 MCI and 68 controls were consecutively evaluated. All patients and controls underwent the Mini Mental State Evaluation (MMSE) and the Lüscher color test.ResultsCognitively impaired patients mainly chose auxiliary colors, in particular violet and brown, and rejected black and gray. AD patients predominantly chose forms corresponding to auxiliary colors. The auxiliary color choice negatively correlated with the MMSE score. MCI patients and controls had a higher presence of anxiety on gray table and controls had higher frustration and ambivalence, i.e., psychic complexity, on basic color tables.Data globally suggest that AD patients live with a feeling of personal change due to instability and emotional insecurity, experiencing physical discomfort and a bodily need of being welcomed in a favorable environment. They aspire to a sensitive understanding by someone with whom they can be identified. Differently, MCI patients have less of these needs; however, they feel more anxious.ConclusionThe comprehension of the inner emotional state of cognitively impaired patients allows us to better communicate with them and effectively approach their behavioral disorders. Like other projective techniques, such as the tree-drawing test and the human figure-drawing test, Lüscher color test is proposed as a simple and unconventional approach to understand the emotional life of AD patients. The awareness of clinicians about the existential fragility and insecurity of such type of patients allows us not only to better manage their behavioral disturbances but also to improve their quality of life and that of their caregivers.

Published
2019
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3. Predicting conversion from mild cognitive impairment to Alzheimer's disease using brain 1H-MRS and volumetric changes: A two- year retrospective follow-up study

Author

Micaela Mitolo, Michelangelo Stanzani-Maserati, Sabina Capellari, Claudia Testa, Paola Rucci, Roberto Poda, Federico Oppi, Roberto Gallassi, Luisa Sambati, Giovanni Rizzo, Piero Parchi, Stefania Evangelisti, Lia Talozzi, Caterina Tonon, Raffaele Lodi, and Rocco Liguori

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429
Abstract

This study investigated the ability of magnetic resonance spectroscopy (1H-MRS) of posterior cingulate cortex (PCC) and brain volumetry to predict the progression from mild cognitive impairment (MCI) to Alzheimer's Disease (AD) on the basis of clinical classification at 2 years follow-up. Thirty-eight MCI patients, eighteen healthy older adults and twenty-three AD patients were included in this study. All participants underwent a brain-MR protocol (1.5 T GE scanner) including high-resolution T1-weighted volumetric sequence (isotropic 1mm3). Voxel-wise differences in brain volumetry were evaluated using FreeSurfer software and all volumes were normalized by the total intracranial volume (TIV). Careful localization of 1H-MRS volume of PCC was performed and data were processed with the LCModel program. MCI patients underwent a complete neuropsychological assessment at baseline and were clinically re-evaluated after a mean of 28 months; twenty-six MCI patients (68.4%) converted to AD and twelve remained stable.At baseline these two MCI subgroups did not differ in the global cognitive level (Mini Mental State Examination, MMSE) or in any of the other cognitive domains; the NAA/ mI ratio in the PCC was able to differentiate MCI converters from those MCI that did not develop AD (p = 0.022) with a level of accuracy (AUC area) of 0.779. A significantly reduced volume of parahippocampal gyrus (p = 0.010) and fusiform gyrus (p = 0.026) were found in the converter MCI subgroup compared to the stable MCI subgroup. The combined use of both N- acetyl-aspartate (NAA)/myo-Inositol (mI) ratio and volume of parahippocampal gyrus, increases the overall accuracy (AUC = 0.910) in predicting the conversion to AD two years before the development of clinical symptoms. Additional longitudinal studies with a broader representative sample of MCI patients and longer follow-up might be helpful to confirm these results and to elucidate the role of each parameter in predicting the possible progression to AD, and also to all the other non-AD dementia subtypes. Keywords: Mild cognitive impairment, MRI, 1H-MRS, Alzheimer's disease

Published
2019
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4. Relationship of white and gray matter abnormalities to clinical and genetic features in myotonic dystrophy type 1

Author

Stefano Zanigni, Stefania Evangelisti, Maria Pia Giannoccaro, Federico Oppi, Roberto Poda, Antonio Giorgio, Claudia Testa, David Neil Manners, Patrizia Avoni, Laura Ludovica Gramegna, Nicola De Stefano, Raffaele Lodi, Caterina Tonon, and Rocco Liguori

Subjects
myotonic dystrophy type 1, DTI, TBSS, VBM, cortical thickness, Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429
Abstract

Background: Myotonic dystrophy type 1 (DM1) represents a multisystemic disorder in which diffuse brain white and gray matter alterations related to clinical and genetic features have been described. We aimed to evaluate in the brain of adult patients with DM1 (i) white and gray matter differences, including cortical-subcortical gray matter volume and cortical thickness and (ii) their correlation with clinical disability, global neuropsychological performance and triplet expansion. Methods: We included 24 adult genetically-confirmed DM1 patients (14 males; age: 38.5 ± 11.8 years) and 25 age- and sex-matched healthy controls (14 males; age: 38.5 ± 11.3 years) who underwent an identical brain MR protocol including high-resolution 3D T1-weighted, axial T2 FLAIR and DTI sequences. All patients underwent an extensive clinical and neuropsychological evaluation. Voxel-wise analyses of white matter, performed by using Tract Based Spatial Statistics, and of gray matter, with Voxel-based Morphometry and Cortical Thickness, were carried out in order to test for differences between patients with DM1 and healthy controls (p

Published
2016
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5. The Tree-Drawing Test (Koch’s Baum Test): A Useful Aid to Diagnose Cognitive Impairment

Author

Michelangelo Stanzani Maserati, Corrado Matacena, Luisa Sambati, Federico Oppi, Roberto Poda, Maddalena De Matteis, and Roberto Gallassi

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Objective. To study the Tree-Drawing Test in a group of demented patients and compare it with a group of mild cognitively impaired patients (MCI) and controls. Methods. Consecutive outpatients were classified as affected by dementia (Alzheimer’s disease (AD), frontotemporal dementia (FTD), and vascular dementia (VD)) or by MCI. Patients and controls underwent the Tree-Drawing Test and MMSE. Results. 118 AD, 19 FTD, 46 VD, and 132 MCI patients and 90 controls were enrolled. AD patients draw trees globally smaller than other patients and controls. FTD patients draw trees with a wider space occupation than AD and MCI patients but smaller than controls as well as VD patients. Trees drawn by MCI patients are intermediate in size between AD patients and controls. The trunk-to-crown ratio of trees drawn by cognitive impaired patients is greater than controls while the tree size-relative-to-page space index is significantly smaller. The tree size-relative-to-page space index of trees drawn by AD patients is smaller than that of the other cognitively impaired patients. Tree height and the trunk-to-crown ratio are independent predictors of cognitive impairment. Conclusions. Trees drawn by cognitively impaired patients are different from those drawn by healthy subjects with a progressive differentiation from mild to more relevant degrees of cognitive impairment.

Published
2015
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6. Cognitive function in peripheral autonomic disorders.

Author

Pietro Guaraldi, Roberto Poda, Giovanna Calandra-Buonaura, Laura Solieri, Luisa Sambati, Roberto Gallassi, and Pietro Cortelli

Subjects
Medicine, Science
Abstract

Objectiveaims of the current study were 1) to evaluate global cognitive function in patients with autonomic failure (AF) of peripheral origin and 2) to investigate the effect of a documented fall in blood pressure (BP) fulfilling the criteria for orthostatic hypotension (OH) on cognitive performances.Methodswe assessed 12 consecutive patients (10 males, 68±7 years old) with pure AF (PAF) or autoimmune autonomic neuropathy (AAN) and 12 age- and gender-matched controls. All patients had no clinical signs of central nervous system involvement and normal brain CT/MRI scan. Cognitive function was assessed on two consecutive days in 3 conditions: on day 1, while sitting, by means of a comprehensive battery of neuropsychological tests; on day 2, while tilted (HUT) and during supine rest (supine) in a randomized manner. BP and heart rate (HR) were continuously recorded non-invasively for the whole duration of the examination.Resultspatients with PAF or AAN displayed a preserved global cognitive function while sitting. However, compared to supine assessment, during HUT patients scored significantly worse during the Trail Making Test A and B, Barrage test, Analogies test, Immediate Visual Memory, Span Forward and Span Backward test. Pathological scores, with regard to Italian normative range values, were observed only during HUT in the Barrage test and in the Analogies test in 3 and 6 patients respectively. On the contrary, in healthy controls, results to neuropsychological tests were not significantly different, during HUT compared to supine rest.Conclusionsthese data demonstrate that patients with PAF and AAN present a normal sitting global cognitive evaluation. However, their executive functions worsen significantly during the orthostatic challenge, possibly because of transient frontal lobes hypoperfusion.

Published
2014
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7. Human figure drawing distinguishes Alzheimer’s patients: a cognitive screening test study

Author

Roberto Poda, Luisa Sambati, Michelangelo Stanzani Maserati, Maddalena De Matteis, Federico Oppi, Ilaria Naldi, Sabina Capellari, Corrado Matacena, Renato D’Onofrio, Rocco Liguori, Michelangelo Stanzani Maserati, Renato D’Onofrio, Corrado Matacena, Luisa Sambati, Federico Oppi, Roberto Poda, Maddalena De Mattei, Ilaria Naldi, Rocco Liguori, and Sabina Capellari

Subjects
Male, Aging, Neurology, Task Performance and Analysi, Audiology, 0302 clinical medicine, Task Performance and Analysis, Qualitative Research, Motor Skill, Neuroradiology, 05 social sciences, General Medicine, Mental Status and Dementia Tests, Test (assessment), Psychiatry and Mental health, Social Perception, Motor Skills, Cognitive screening, Linear Model, Female, Neurosurgery, Mental Status and Dementia Test, Alzheimer's disease, Alzheimer’s disease, Personality, Human, medicine.medical_specialty, Figure drawing, Dermatology, 050105 experimental psychology, Diagnosis, Differential, Human figure drawing, 03 medical and health sciences, Alzheimer Disease, mental disorders, medicine, Humans, Dementia, Cognitive Dysfunction, 0501 psychology and cognitive sciences, Aged, business.industry, Mild cognitive impairment, medicine.disease, Linear Models, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

To study human figure drawing in a group of Alzheimer's disease (AD) patients and compare it with a group of patients with mild cognitive impairment (MCI) and controls. We evaluated consecutive outpatients over a one-year period. Patients were classified as affected by AD or by MCI. All patients and controls underwent a simplified version of the human-figure drawing test and MMSE. A qualitative and quantitative analysis of all human figures was obtained. 112 AD, 100 MCI patients and 104 controls were enrolled. AD patients drew human figures poor in details and globally smaller than MCI patients and controls. Human figures drawn by MCI patients are intermediate in body height between those of the AD patients and the healthy subjects. The head-to-body ratio of human figures drawn by AD patients is greater than controls and MCI patients, while the human figure size-relative-to-page space index is significantly smaller. Body height is an independent predictor of cognitive impairment correlating with its severity and with the number of the figure's details. Human figures drawn by AD patients are different from those drawn by healthy subjects and MCI patients. Human figure drawing test is a useful tool for orienting cognitive impairment's diagnosis.

Published
2018

8. The Combination of Metabolic Posterior Cingulate Cortical Abnormalities and Structural Asymmetries Improves the Differential Diagnosis Between Primary Progressive Aphasia and Alzheimer's Disease

Author

Claudia Testa, Micaela Mitolo, Caterina Tonon, Stefania Evangelisti, Michelangelo Stanzani-Maserati, Roberto Poda, David Neil Manners, Rocco Liguori, Sabina Capellari, Laura Ludovica Gramegna, Raffaele Lodi, Federico Oppi, Lia Talozzi, Silvia Magarelli, Roberta Pantieri, Mitolo M., Stanzani-Maserati M., Manners D.N., Capellari S., Testa C., Talozzi L., Poda R., Oppi F., Evangelisti S., Gramegna L.L., Magarelli S., Pantieri R., Liguori R., Lodi R., and Tonon C.

Subjects
Male, Pathology, medicine.medical_specialty, Magnetic Resonance Spectroscopy, Disease, Neuropsychological Tests, Gyrus Cinguli, 030218 nuclear medicine & medical imaging, Primary progressive aphasia, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Atrophy, Cortical abnormalities, Alzheimer Disease, Cortex (anatomy), medicine, magnetic resonance imaging, Humans, H-MRS, Aged, medicine.diagnostic_test, business.industry, General Neuroscience, Brain, Magnetic resonance imaging, General Medicine, respiratory system, Alzheimer's disease, medicine.disease, Psychiatry and Mental health, Clinical Psychology, medicine.anatomical_structure, Aphasia, Primary Progressive, Posterior cingulate, primary progressive aphasia, Neuropsychological Test, Female, Geriatrics and Gerontology, Differential diagnosis, business, 030217 neurology & neurosurgery, Human
Abstract

Differential diagnosis between primary progressive aphasia (PPA) and Alzheimer’s disease (AD) could be difficult if based on clinical grounds alone. We evaluated the combination of proton MR spectroscopy of posterior cingulate cortex (PCC) and quantitative structural imaging asymmetries to differentiate PPA from AD patients. A greater left-lateralized temporo-parietal atrophy (higher accuracy for the PCC, 81.4%) and metabolic neurodegenerative changes in PCC (accuracy 76.8%) was demonstrated in PPA versus AD. The combined multiparametric approach increased the accuracy to 94%in the differential diagnosis between these two neurodegenerative diseases.

Published
2021

9. Effects on cognition of 20-day anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex in patients affected by mild cognitive impairment: a case-control study

Author

Federico Oppi, Sabina Capellari, Giovanni Rizzo, Roberto Poda, Vitantonio Di Stasi, Patrizia Avoni, Michelangelo Stanzani-Maserati, Rocco Liguori, E. Fileccia, Fileccia, Enrico, Di Stasi, Vitantonio, Poda, Roberto, Rizzo, Giovanni, Stanzani-Maserati, Michelangelo, Oppi, Federico, Avoni, Patrizia, Capellari, Sabina, and Liguori, Rocco

Subjects
Male, medicine.medical_specialty, Memory, Episodic, medicine.medical_treatment, Prefrontal Cortex, Dermatology, Neuropsychological Tests, Audiology, DLPFC, Transcranial Direct Current Stimulation, tDCS, 03 medical and health sciences, Cognition, 0302 clinical medicine, Neuropsychology, Neuromodulation, medicine, Humans, Cognitive Dysfunction, 030212 general & internal medicine, Aged, Language, Transcranial direct-current stimulation, business.industry, Beck Depression Inventory, Mild cognitive impairment, Repeated measures design, General Medicine, MCI, Affect, Psychiatry and Mental health, Treatment Outcome, medicine.anatomical_structure, Mood, Pattern Recognition, Visual, Case-Control Studies, Female, Neurology (clinical), Verbal memory, business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract

Mild cognitive impairment (MCI) is a common disorder affecting as much as 15% of the elderly population. Transcranial direct current stimulation (tDCS) is a non-invasive technique of neuromodulation that has proven to influence performance in different cognitive domains. We investigated the effects on cognition of 20-day anodal tDCS in 17 MCI patients compared with 17 matched MCI patients. Patients underwent neuropsychological evaluation at baseline and then were randomly assigned to the anodal or sham group. The tDCS protocol consisted in 20 min, 5 days per week (up to a total of 20 days), of 2-mA anodal stimulation over the left dorsolateral prefrontal cortex (DLPFC). The location of anodal electrode was chosen in accordance with previous reports which relate anodal stimulation of this site with cognitive enhancement. At the end of the last day of stimulation, a second neuropsychological evaluation was performed. We compared baseline and post-stimulation neuropsychological results in the anodal vs sham group using repeated measures ANOVA as a statistical analysis test. At follow-up, patients exposed to anodal stimulation showed improvement in episodic verbal memory (p

Published
2019

10. Identification of genetic variants associated with Huntington's disease progression

Author

Davina J Hensman Moss, Antonio F Pardiñas, Douglas Langbehn, Kitty Lo, Blair R Leavitt, Raymund Roos, Alexandra Durr, Simon Mead, Peter Holmans, Lesley Jones, Sarah J Tabrizi, A Coleman, R Dar Santos, J Decolongon, A Sturrock, E Bardinet, C Jauff Ret, D Justo, S Lehericy, C Marelli, K Nigaud, R Valabrègue, SJA van den Bogaard, E M Dumas, J van der Grond, EP t'Hart, C Jurgens, M-N Witjes-Ane, N Arran, J Callaghan, C Stopford, C Frost, R Jones, N Hobbs, N Lahiri, R Ordidge, G Owen, T Pepple, J Read, M Say, E Wild, A Patel, N C Fox, C Gibbard, I Malone, H Crawford, D Whitehead, S Keenan, D M Cash, C Berna, N Bechtel, S Bohlen, A Hoff Man, P Kraus, E Axelson, C Wang, T Acharya, S Lee, W Monaco, C Campbell, S Queller, K Whitlock, M Campbell, E Frajman, C Milchman, A O'Regan, I Labuschagne, J Stout, B Landwehrmeyer, D Craufurd, R Scahill, S Hicks, C Kennard, H Johnson, A Tobin, HD Rosas, R Reilmann, B Borowsky, C Pourchot, S C Andrews, Anne-Catherine Bachoud-Lévi, Anna Rita Bentivoglio, Ida Biunno, Raphael Bonelli, Jean-Marc Burgunder, Stephen Dunnett, Joaquim Ferreira, Olivia Handley, Arvid Heiberg, Torsten Illmann, G. Bernhard Landwehrmeyer, Jamie Levey, Maria A. Ramos-Arroyo, Jørgen Nielsen, Susana Pro Koivisto, Markku Päivärinta, Raymund A.C. Roos, A Rojo Sebastián, Sarah Tabrizi, Wim Vandenberghe, Christine Verellen-Dumoulin, Tereza Uhrova, Jan Wahlström, Jacek Zaremba, Verena Baake, Katrin Barth, Monica Bascuñana Garde, Sabrina Betz, Reineke Bos, Jenny Callaghan, Adrien Come, Leonor Correia Guedes, Daniel Ecker, Ana Maria Finisterra, Ruth Fullam, Mette Gilling, Lena Gustafsson, Olivia J Handley, Carina Hvalstedt, Christine Held, Kerstin Koppers, Claudia Lamanna, Matilde Laurà, Asunción Martínez Descals, Saül Martinez-Horta, Tiago Mestre, Sara Minster, Daniela Monza, Lisanne Mütze, Martin Oehmen, Michael Orth, Hélène Padieu, Laurent Paterski, Nadia Peppa, Martina Di Renzo, Amandine Rialland, Niini Røren, Pavla Šašinková, Erika Timewell, Jenny Townhill, Patricia Trigo Cubillo, Wildson Vieira da Silva, Marleen R van Walsem, Carina Whalstedt, Marie-Noelle Witjes-Ané, Grzegorz Witkowski, Abigail Wright, Daniel Zielonka, Eugeniusz Zielonka, Paola Zinzi, Raphael M. Bonelli, Sabine Lilek, Karen Hecht, Brigitte Herranhof, Anna Holl, Hans-Peter Kapfhammer, Michael Koppitz, Markus Magnet, Nicole Müller, Daniela Otti, Annamaria Painold, Karin Reisinger, Monika Scheibl, Helmut Schöggl, Jasmin Ullah, Eva-Maria Braunwarth, Florian Brugger, Lisa Buratti, Eva-Maria Hametner, Caroline Hepperger, Christiane Holas, Anna Hotter, Anna Hussl, Christoph Müller, Werner Poewe, Klaus Seppi, Fabienne Sprenger, Gregor Wenning, Andrea Boogaerts, Godelinde Calmeyn, Isabelle Delvaux, Dirk Liessens, Nele Somers, Michel Dupuit, Cécile Minet, Dominique van Paemel, Pascale Ribaï, Dimphna van Reijen, Jirí Klempír, Veronika Majerová, Jan Roth, Irena Stárková, Lena E. Hjermind, Oda Jacobsen, Jørgen E. Nielsen, Ida Unmack Larsen, Tua Vinther-Jensen, Heli Hiivola, Hannele Hyppönen, Kirsti Martikainen, Katri Tuuha, Philippe Allain, Dominique Bonneau, Marie Bost, Bénédicte Gohier, Marie-Anne Guérid, Audrey Olivier, Adriana Prundean, Clarisse Scherer-Gagou, Christophe Verny, Blandine Babiloni, Sabrina Debruxelles, Charlotte Duché, Cyril Goizet, Laetitia Jameau, Danielle Lafoucrière, Umberto Spampinato, Rekha Barthélémy, Christelle De Bruycker, Maryline Cabaret Anne-Sophie Carette, Eric Decorte Luc Defebvre, Marie Delliaux, Arnaud Delval, Alain Destee, Kathy Dujardin, Marie-Hélène Lemaire, Sylvie Manouvrier, Mireille Peter, Lucie Plomhouse, Bernard Sablonnière, Clémence Simonin, Stéphanie Thibault-Tanchou, Isabelle Vuillaume, Marcellin Bellonet, Hassan Berrissoul, Stéphanie Blin, Françoise Courtin, Cécile Duru, Véronique Fasquel, Olivier Godefroy, Pierre Krystkowiak, Béatrice Mantaux, Martine Roussel, Sandrine Wannepain, Jean-Philippe Azulay, Marie Delfini, Alexandre Eusebio, Frédérique Fluchere, Laura Mundler, Mathieu Anheim, Celine Julié, Ouhaid Lagha Boukbiza, Nadine Longato, Gabrielle Rudolf, Christine Tranchant, Marie-Agathe Zimmermann, Christoph Michael Kosinski, Eva Milkereit, Daniela Probst, Kathrin Reetz, Christian Sass, Johannes Schiefer, Christiane Schlangen, Cornelius J. Werner, Harald Gelderblom, Josef Priller, Harald Prüß, Eike Jakob Spruth, Gisa Ellrichmann, Lennard Herrmann, Rainer Hoffmann, Barbara Kaminski, Peter Kotz, Christian Prehn, Carsten Saft, Herwig Lange, Robert Maiwald, Matthias Löhle, Antonia Maass, Simone Schmidt, Cecile Bosredon, Alexander Storch, Annett Wolz, Martin Wolz, Philipp Capetian, Johann Lambeck, Birgit Zucker, Kai Boelmans, Christos Ganos, Walburgis Heinicke, Ute Hidding, Jan Lewerenz, Alexander Münchau, Jenny Schmalfeld, Lars Stubbe, Simone Zittel, Gabriele Diercks, Dirk Dressler, Heike Gorzolla, Christoph Schrader, Pawel Tacik, Michael Ribbat, Bernhard Longinus, Katrin Bürk, Jens Carsten Möller, Ida Rissling, Mark Mühlau, Alexander Peinemann, Michael Städtler, Adolf Weindl, Juliane Winkelmann, Cornelia Ziegler, Natalie Bechtel, Heike Beckmann, Stefan Bohlen, Eva Hölzner, Ralf Reilmann, Stefanie Rohm, Silke Rumpf, Sigrun Schepers, Natalia Weber, Matthias Dose, Gabriele Leythäuser, Ralf Marquard, Tina Raab, Alexandra Wiedemann, Andrea Buck, Julia Connemann, Carolin Geitner, Andrea Kesse, Bernhard Landwehrmeyer, Christina Lang, Franziska Lezius, Solveig Nepper, Anke Niess, Ariane Schneider, Daniela Schwenk, Sigurd Süßmuth, Sonja Trautmann, Patrick Weydt, Claudia Cormio, Vittorio Sciruicchio, Claudia Serpino, Marina de Tommaso, Sabina Capellari, Pietro Cortelli, Roberto Galassi, Giovanni Rizzo, Roberto Poda, Cesa Scaglione, Elisabetta Bertini, Elena Ghelli, Andrea Ginestroni, Francesca Massaro, Claudia Mechi, Marco Paganini, Silvia Piacentini, Silvia Pradella, Anna Maria Romoli, Sandro Sorbi, Giovanni Abbruzzese, Monica Bandettini di Poggio, Giovanna Ferrandes, Paola Mandich, Roberta Marchese, Alberto Albanese, Daniela Di Bella, Anna Castaldo, Stefano Di Donato, Cinzia Gellera, Silvia Genitrini, Caterina Mariotti, Lorenzo Nanetti, Dominga Paridi, Paola Soliveri, Chiara Tomasello, Giuseppe De Michele, Luigi Di Maio, Marco Massarelli, Silvio Peluso, Alessandro Roca, Cinzia Valeria Russo, Elena Salvatore, Pierpaolo Sorrentino, Enrico Amico, Mariagrazia Favellato, Annamaria Griguoli, Irene Mazzante, Martina Petrollini, Ferdinando Squitieri, Barbara D'Alessio, Chiara Esposito, Rita Bentivoglio, Marina Frontali, Arianna Guidubaldi, Tamara Ialongo, Gioia Jacopini, Carla Piano, Silvia Romano, Francesco Soleti, Maria Spadaro, Monique S.E. van Hout, Marloes E. Verhoeven, Jeroen P.P. van Vugt, A. Marit de Weert, J.J.W. Bolwijn, M. Dekker, B. Kremer, K.L. Leenders, J.C.H. van Oostrom, Simon J.A. van den Bogaard, Eve M. Dumas, Ellen P. 't Hart, Berry Kremer, C.C.P. Verstappen, Olaf Aaserud, Jan Frich C, Ragnhild Wehus, Kathrine Bjørgo, Madeleine Fannemel, Per F. 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P., Aaserud, Olaf, Jan Frich, C., Wehus, Ragnhild, Bjã¸rgo, Kathrine, Fannemel, Madeleine, Gã¸rvell, Per F., Lorentzen, Eirin, Retterstã¸l, Lar, Stokke, Bodil, Bjã¸rnevoll, Inga, Sando, Sigrid Botne, Dziadkiewicz, Artur, Nowak, Malgorzata, Robowski, Piotr, Sitek, Emilia, Slawek, Jaroslaw, Soltan, Witold, Szinwelski, Michal, Blaszcyk, Magdalena, Boczarska-Jedynak, Magdalena, Ciach-Wysocka, Ewelina, Gorzkowska, Agnieszka, Jasinska-Myga, Barbara, Klodowska-Duda, Gabriela, Opala, Gregorz, Stompel, Daniel, Banaszkiewicz, Krzysztof, Bocwinska, Dorota, Bojakowska-Jaremek, Kamila, Dec, Malgorzata, Krawczyk, Malgorzata, Rudzinska, Monika, Szczygiel, Elzbieta, Szczudlik, Andrzej, Wasielewska, Anna, Wã³jcik, Magdalena, Bryl, Anna, Ciesielska, Anna, Klimberg, Aneta, Marcinkowski, Jerzy, Samara, Husam, Sempolowicz, Justyna, Gogol, Anna, Janik, Piotr, Kwiecinski, Hubert, Jamrozik, Zygmunt, Antczak, Jakub, Jachinska, Katarzyna, Krysa, Wioletta, Rakowicz, Maryla, Richter, Przemyslaw, Rola, Rafal, Ryglewicz, Danuta, Sienkiewicz-Jarosz, Halina, Stepniak, Iwona, Sulek, Anna, Zdzienicka, Elzbieta, Zieora-Jakutowicz, Karolina, Ferreira, Joaquim J, Coelho, Miguel, Mendes, Tiago, Valadas, Anabela, Andrade, Carlo, Gago, Miguel, Garrett, Carolina, Guerra, Maria Rosália, Herrera, Carmen Durán, Garcia, Patrocinio Moreno, Barbera, Miquel Aguilar, Guia, Dolors Badene, Hernanz, Laura Casa, Catena, Judit López, Ferrer, Pilar Quiléz, Sebastiã¡n, Ana Rojo, Carruesco, Gemma Tome, Bas, Jordi, Busquets, Nãºria, Calopa, Matilde, Robert, Misericordia Floriach, Viladrich, Celia Mareca, Idiago, Jesús Miguel Ruiz, Riballo, Antonio Villa, Cubo, Esther, Polo, Cecilia Gil, Mariscal, Natividad, Rivadeneyra, Perez Jessica, Barrero, Francisco, Morales, Bla, Fenollar, Marã­a, Garcã­a, Rocío García-Ramo, Ortega, Paloma, Villanueva, Clara, Alegre, Javier, Bascuã±ana, Mã³nica, Caldentey, Juan Garcia, Ventura, Marta Fatá, Ribas, Guillermo García, de Yébenes, Justo García, Moreno, José Luis López-Sendón, Frech, Fernando Alonso, Ruã­z, Pedro J. García, Martínez-Descals, Asunciã³n, Guerrero, Rosa, Artiga, María José Saiz, Sã¡nchez, Vicenta, Perea, María Fuensanta Noguera, Fortuna, Lorenza, Manzanares, Salvadora, Reinante, Gema, Torres, María Martirio Antequera, Moreau, Laura Vivanco, González González, Sonia, Guisasola, Luis Menéndez, Salvador, Carlo, Martã­n, Esther Suaréz San, Ramirez, Inés Legarda, Gorospe, Aranzazãº, Lopera, Mónica Rodriguez, Arques, Penelope Nava, Rodrã­guez, María José Torre, Pastor, Barbara Vive, Gaston, Itziar, Martinez-Jaurrieta, Maria Dolore, Moreno, Jose Manuel Garcia, Lucena, Carolina Mendez, Damas, Fatima, Cortegana, Hermoso Eva Pacheco, Peã±a, José Chacón, Redondo, Lui, Carrillo, Fã¡tima, Teresa Cáceres, Marã­a, Mir, Pablo, Suarez, María José Lama, Vargas-González, Laura, Bosca, Maria E., Brugada, Francisco Castera, Burguera, Juan Andre, Campos, Anabel, Vilaplana, Garcia Carmen Peiró, Berglund, Peter, Constantinescu, Radu, Fredlund, Gunnel, Høsterey-Ugander, Ulrika, Linnsand, Petra, Neleborn-Lingefjärd, Liselotte, Wentzel, Magnu, Loutfi, Ghada, Olofsson, Carina, Stattin, Eva-Lena, Westman, Laila, Wikstrã¶m, Birgitta, Stebler, Yanik, Kaelin, Alain, Romero, Irene, Schã¼pbach, Michael, Weber Zaugg, Sabine, Hauer, Maria, Gonzenbach, Roman, Jung, Hans H., Mihaylova, Violeta, Petersen, Jen, Jack, Roisin, Matheson, Kirsty, Miedzybrodzka, Zosia, Rae, Daniela, Simpson, Sheila A, Summers, Fiona, Ure, Alexandra, Vaughan, Vivien, Akhtar, Shahbana, Crooks, Jenny, Curtis, Adrienne, de Souza, Jenny, Piedad, John, Rickards, Hugh, Wright, Jan, Coulthard, Elizabeth, Gethin, Louise, Hayward, Beverley, Sieradzan, Kasia, Armstrong, Matthew, Barker, Roger A., O'Keefe, Deidre, Di Pietro, Anna, Fisher, Kate, Goodman, Anna, Hill, Susan, Kershaw, Ann, Mason, Sarah, Paterson, Nicole, Raymond, Lucy, Swain, Rachel, Guzman, Natalie Valle, Busse, Monica, Butcher, Cynthia, Clenaghan, Catherine, Hunt, Sarah, Jones, Una, Khalil, Hanan, Owen, Michael, Price, Kathleen, Rosser, Anne, Edwards, Maureen, Carrie, Ho, Hughes, Teresa, Mcgill, Marie, Pearson, Pauline, Porteous, Mary, Smith, Paul, Brockie, Peter, Foster, Jillian, Johns, Nicola, Mckenzie, Sue, Rothery, Jean, Thomas, Gareth, Yates, Shona, Burrows, Liz, Chu, Carol, Fletcher, Amy, Gallantrae, Deena, Hamer, Stephanie, Harding, Alison, Klã¶ppel, Stefan, Kraus, Alison, Laver, Fiona, Lewis, Monica, Longthorpe, Mandy, Markova, Ivana, Raman, Ashok, Robertson, Nicola, Silva, Mark, Thomson, Aileen, Wild, Sue, Yardumian, Pam, Evans, Carole, Gallentrae, Deena, Hobson, Emma, Jamieson, Stuart, Musgrave, Hannah, Rowett, Liz, Toscano, Jean, Bourne, Colin, Clapton, Jackie, Clayton, Carole, Dipple, Heather, Freire-Patino, Dawn, Grant, Janet, Gross, Diana, Hallam, Caroline, Middleton, Julia, Murch, Ann, Thompson, Catherine, Alusi, Sundu, Davies, Rhy, Foy, Kevin, Gerrans, Emily, Pate, Louise, Andrews, Thomasin, Dougherty, Andrew, Golding, Charlotte, Kavalier, Fred, Laing, Hana, Lashwood, Alison, Robertson, Dene, Ruddy, Deborah, Santhouse, Alastair, Whaite, Anna, Bruno, Stefania, Doherty, Karen, Haider, Salman, Hensman, Davina, Lahiri, Nayana, Novak, Marianne, Patel, Aakta, Rosser, Elisabeth, Taylor, Rachel, Warner, Thoma, Wild, Edward, Arran, Natalie, Bek, Judith, Craufurd, David, Hare, Marianne, Howard, Liz, Huson, Susan, Johnson, Liz, Jones, Mary, Murphy, Helen, Oughton, Emma, Partington-Jones, Lucy, Rogers, Dawn, Sollom, Andrea, Snowden, Julie, Stopford, Cheryl, Thompson, Jennifer, Trender-Gerhard, Iri, Verstraelen, Nichola, Westmoreland, Leann, Armstrong, Richard, Dixon, Kathryn, Nemeth, Andrea H, Siuda, Gill, Valentine, Ruth, David, Harrison, Hughes, Max, Parkinson, Andrew, Soltysiak, Beverley, Bandmann, Oliver, Bradbury, Alyson, Gill, Paul, Fairtlough, Helen, Fillingham, Kay, Foustanos, Isabella, Kazoka, Mbombe, O'Donovan, Kirsty, Taylor, Cat, Tidswell, Katherine, Quarrell, Oliver, Lau, Puay Ngoh, Pica, Emmanul, Tan, Louis, Amsterdam Neuroscience - Neurodegeneration, Neurology, Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Moss, Davina J Hensman, Lo, Kitty, Pardiñas, Antonio F, Santos, R Dar, Ret, C Jauff, Valabrègue, R., Witjes-Ane, M. -N., Man, A Hoff, Bachoud-Lévi, Anne-Catherine, Nielsen, Jørgen, Päivärinta, Markku, Sebastián, A Rojo, Wahlström, Jan, Garde, Monica Bascuñana, Laurà, Matilde, Descals, Asunción Martínez, Martinez-Horta, Saül, Mütze, Lisanne, Padieu, Hélène, Røren, Niini, Šašinková, Pavla, Witjes-Ané, Marie-Noelle, Müller, Nicole, Schöggl, Helmut, Müller, Christoph, Minet, Cécile, Ribaï, Pascale, Klempír, Jirí, Majerová, Veronika, Stárková, Irena, Nielsen, Jørgen E., Hyppönen, Hannele, Gohier, Bénédicte, Guérid, Marie-Anne, Duché, Charlotte, Lafoucrière, Danielle, Barthélémy, Rekha, Lemaire, Marie-Hélène, Sablonnière, Bernard, Simonin, Clémence, Thibault-Tanchou, Stéphanie, Blin, Stéphanie, Courtin, Françoise, Duru, Cécile, Fasquel, Véronique, Mantaux, Béatrice, Fluchere, Frédérique, Julié, Celine, Prüß, Harald, Löhle, Matthia, Münchau, Alexander, Bürk, Katrin, Möller, Jens Carsten, Mühlau, Mark, Städtler, Michael, Hölzner, Eva, Leythäuser, Gabriele, Süßmuth, Sigurd, Marchese, Roberta, DI MAIO, Luigi, ’t Hart, Ellen P., Bjørgo, Kathrine, Gørvell, Per F., Retterstøl, Lar, Bjørnevoll, Inga, Wójcik, Magdalena, Guerra, Maria Rosália, Herrera, Carmen Durán, Catena, Judit López, Ferrer, Pilar Quiléz, Sebastián, Ana Rojo, Busquets, Núria, Idiago, Jesús Miguel Ruiz, Fenollar, María, García, Rocío García-Ramo, Bascuñana, Mónica, Ventura, Marta Fatá, Ribas, Guillermo García, de Yébenes, Justo García, Moreno, José Luis López-Sendón, Ruíz, Pedro J García, Martínez-Descals, Asunción, Artiga, María José Saiz, Sánchez, Vicenta, Perea, María Fuensanta Noguera, Torres, María Martirio Antequera, González González, Sonia, Guisasola, Luis Menéndez, Martín, Esther Suaréz San, Ramirez, Inés Legarda, Gorospe, Aranzazú, Lopera, Mónica Rodriguez, Rodríguez, María José Torre, Peña, José Chacón, Carrillo, Fátima, Teresa Cáceres, María, Suarez, María José Lama, Vargas-González, Laura, Vilaplana, Garcia Carmen Peiró, Høsterey-Ugander, Ulrika, Neleborn-Lingefjärd, Liselotte, Wikström, Birgitta, Schüpbach, Michael, Ho, Carrie, Klöppel, Stefan, Harrison, David, Cardiff University, University of Iowa [Iowa City], University of British Columbia (UBC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UCL, Institute of Neurology [London], National Oceanography Centre [Southampton] (NOC), University of Southampton, Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), IFR de Neuroimagerie Fonctionnelle (IFR 49), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Amiens-Picardie, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), TRACK-HD investigators, Pardinas, Antonio F, Langbehn, Douglas, Lee, S Hong, TRACK-HD Investigators, and REGISTRY Investigators

Subjects
0301 basic medicine, Oncology, Registrie, Genome-wide association study, Longitudinal Studie, Disease, Bioinformatics, Severity of Illness Index, Principal Component Analysi, Longitudinal Studies, Registries, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Huntington disease, DNA-Binding Proteins, Settore MED/26 - NEUROLOGIA, Adult, Genome-Wide Association Study, Humans, Huntington Disease, MutS Homolog 3 Protein, Principal Component Analysis, Disease Progression, Neurology (clinical), huntingtin gene, age of onest, Huntington’s disease, Human, medicine.medical_specialty, cag repeat, instability, DNA-Binding Protein, Clinical Neurology, Principal component analysis, Single-nucleotide polymorphism, Biology, 03 medical and health sciences, Huntington's disease, Internal medicine, medicine, SNP, genome-wide association study, medicine.disease, R1, meta-analysis, Minor allele frequency, 030104 developmental biology, Age of onset, Trinucleotide repeat expansion, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation. Funding The European Commission FP7 NeurOmics project; CHDI Foundation; the Medical Research Council UK; the Brain Research Trust; and the Guarantors of Brain.

Published
2017

11. Predicting conversion from mild cognitive impairment to Alzheimer's disease using brain

Author

Micaela, Mitolo, Michelangelo, Stanzani-Maserati, Sabina, Capellari, Claudia, Testa, Paola, Rucci, Roberto, Poda, Federico, Oppi, Roberto, Gallassi, Luisa, Sambati, Giovanni, Rizzo, Piero, Parchi, Stefania, Evangelisti, Lia, Talozzi, Caterina, Tonon, Raffaele, Lodi, and Rocco, Liguori

Subjects
Aged, 80 and over, Male, Proton Magnetic Resonance Spectroscopy, Brain, Regular Article, Middle Aged, Neuropsychological Tests, Alzheimer Disease, Predictive Value of Tests, mental disorders, Disease Progression, Humans, Cognitive Dysfunction, Female, Aged, Follow-Up Studies, Retrospective Studies
Abstract

This study investigated the ability of magnetic resonance spectroscopy ((1)H-MRS) of posterior cingulate cortex (PCC) and brain volumetry to predict the progression from mild cognitive impairment (MCI) to Alzheimer's Disease (AD) on the basis of clinical classification at 2 years follow-up. Thirty-eight MCI patients, eighteen healthy older adults and twenty-three AD patients were included in this study. All participants underwent a brain-MR protocol (1.5 T GE scanner) including high-resolution T1-weighted volumetric sequence (isotropic 1mm(3)). Voxel-wise differences in brain volumetry were evaluated using FreeSurfer software and all volumes were normalized by the total intracranial volume (TIV). Careful localization of (1)H-MRS volume of PCC was performed and data were processed with the LCModel program. MCI patients underwent a complete neuropsychological assessment at baseline and were clinically re-evaluated after a mean of 28 months; twenty-six MCI patients (68.4%) converted to AD and twelve remained stable. At baseline these two MCI subgroups did not differ in the global cognitive level (Mini Mental State Examination, MMSE) or in any of the other cognitive domains; the NAA/ mI ratio in the PCC was able to differentiate MCI converters from those MCI that did not develop AD (p = 0.022) with a level of accuracy (AUC area) of 0.779. A significantly reduced volume of parahippocampal gyrus (p = 0.010) and fusiform gyrus (p = 0.026) were found in the converter MCI subgroup compared to the stable MCI subgroup. The combined use of both N- acetyl-aspartate (NAA)/myo-Inositol (mI) ratio and volume of parahippocampal gyrus, increases the overall accuracy (AUC = 0.910) in predicting the conversion to AD two years before the development of clinical symptoms. Additional longitudinal studies with a broader representative sample of MCI patients and longer follow-up might be helpful to confirm these results and to elucidate the role of each parameter in predicting the possible progression to AD, and also to all the other non-AD dementia subtypes.

Published
2018

12. Characterization of novel progranulin gene variants in Italian patients with neurodegenerative diseases

Author

Francesca Pastorelli, Fabrizio Salvi, Rocco Liguori, Simone Baiardi, Roberto Poda, Ilaria Bartolomei, Sabina Capellari, Giacomo Mengozzi, Michelangelo Stanzani Maserati, Anna Bartoletti-Stella, Martina Tarozzi, Silvia de Pasqua, Piero Parchi, Silvia Piras, Giuseppe Orio, Alberto Raggi, Bartoletti-Stella A., De Pasqua S., Baiardi S., Bartolomei I., Mengozzi G., Orio G., Pastorelli F., Piras S., Poda R., Raggi A., Maserati M.S., Tarozzi M., Liguori R., Salvi F., Parchi P., and Capellari S.

Subjects
Male, 0301 basic medicine, Progranulin, Aging, Genetic counseling, Genetic Counseling, Biology, Neurodegenerative disease, medicine.disease_cause, Cohort Studies, 03 medical and health sciences, Progranulins, 0302 clinical medicine, Loss of Function Mutation, Genetic variation, medicine, Humans, Missense mutation, Gene, Genetics, Mutation, General Neuroscience, Genetic Variation, Neurodegenerative Diseases, Frontotemporal lobar degeneration, medicine.disease, Genetics, Population, 030104 developmental biology, Italy, Female, Neurology (clinical), Frontotemporal Lobar Degeneration, Geriatrics and Gerontology, Haploinsufficiency, Frontotemporal dementia, 030217 neurology & neurosurgery, Developmental Biology
Abstract

Loss-of-function mutations in the gene encoding for the protein progranulin (PGRN), GRN, are one of the major genetic abnormalities involved in frontotemporal lobar degeneration. However, genetic variations, mainly missense, in GRN have also been linked to other neurodegenerative diseases. We found 12 different pathogenic/likely pathogenic variants in 21 patients identified in a cohort of Italian patients affected by various neurodegenerative disorders. We detected the p.Thr272SerfsTer10 as the most frequent, followed by the c.1179+3A>G variant. We characterized the clinical phenotype of 12 patients from 3 pedigrees carrying the c.1179+3A>G variant, demonstrated the pathogenicity of this mutation, and detected other rarer variants causing haploinsufficiency (p.Met1?, c.709-2A>T, p.Gly79AspfsTer39). Finally, by applying bioinformatics, neuropathological, and biochemical studies, we characterized 6 missense/synonymous variants (p.Asp94His, p.Gly117Asp, p.Ala266Pro, p.Val279Val, p.Arg298His, p.Ala505Gly), including 4 previously unreported. The designation of variants is crucial for genetic counseling and the enrollment of patients in clinical studies.

Published
2021

13. Relationship of white and gray matter abnormalities to clinical and genetic features in myotonic dystrophy type 1

Author

Nicola De Stefano, Rocco Liguori, Roberto Poda, David Neil Manners, Antonio Giorgio, Patrizia Avoni, Stefania Evangelisti, Federico Oppi, Maria Pia Giannoccaro, Caterina Tonon, Claudia Testa, Laura Ludovica Gramegna, Raffaele Lodi, Stefano Zanigni, Zanigni, Stefano, Evangelisti, Stefania, Giannoccaro, Maria Pia, Oppi, Federico, Poda, Roberto, Giorgio, Antonio, Testa, Claudia, Manners, David Neil, Avoni, Patrizia, Gramegna, Laura Ludovica, De Stefano, Nicola, Lodi, Raffaele, Tonon, Caterina, and Liguori, Rocco

Subjects
Male, 0301 basic medicine, Pathology, Neurology, Neuropsychological Tests, Severity of Illness Index, Brain mapping, lcsh:RC346-429, 0302 clinical medicine, Nuclear Medicine and Imaging, Myotonic Dystrophy, Gray Matter, cortical thickne, VBM, cortical thickness, DTI, myotonic dystrophy type 1, TBSS, Neurology (clinical), Radiology, Nuclear Medicine and Imaging, Cognitive Neuroscience, Brain Mapping, medicine.diagnostic_test, Myotonin-protein kinase, Neuropsychology, Regular Article, Middle Aged, Magnetic Resonance Imaging, White Matter, medicine.anatomical_structure, lcsh:R858-859.7, Female, Radiology, Psychology, Adult, musculoskeletal diseases, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, lcsh:Computer applications to medicine. Medical informatics, Myotonic dystrophy, Myotonin-Protein Kinase, Statistics, Nonparametric, White matter, 03 medical and health sciences, Imaging, Three-Dimensional, medicine, Humans, Radiology, Nuclear Medicine and imaging, lcsh:Neurology. Diseases of the nervous system, Magnetic resonance imaging, medicine.disease, 030104 developmental biology, Case-Control Studies, Trinucleotide Repeat Expansion, Trinucleotide repeat expansion, 030217 neurology & neurosurgery
Abstract

Background Myotonic dystrophy type 1 (DM1) represents a multisystemic disorder in which diffuse brain white and gray matter alterations related to clinical and genetic features have been described. We aimed to evaluate in the brain of adult patients with DM1 (i) white and gray matter differences, including cortical-subcortical gray matter volume and cortical thickness and (ii) their correlation with clinical disability, global neuropsychological performance and triplet expansion. Methods We included 24 adult genetically-confirmed DM1 patients (14 males; age: 38.5 ± 11.8 years) and 25 age- and sex-matched healthy controls (14 males; age: 38.5 ± 11.3 years) who underwent an identical brain MR protocol including high-resolution 3D T1-weighted, axial T2 FLAIR and DTI sequences. All patients underwent an extensive clinical and neuropsychological evaluation. Voxel-wise analyses of white matter, performed by using Tract Based Spatial Statistics, and of gray matter, with Voxel-based Morphometry and Cortical Thickness, were carried out in order to test for differences between patients with DM1 and healthy controls (p, Highlights • We investigated DM1 brain abnormalities with TBSS, VBM and cortical thickness analysis. • White matter lesion refilling has been performed to improve voxel-wise analyses. • All patients have been evaluated using a clinical scale created ad hoc for DM1. • DM1 patients present diffuse white and cortical-subcortical gray matter disruption. • White matter differences are correlated with clinical and genetic features.

Published
2016

14. Cerebrospinal Fluid Biomarkers in Patients with Frontotemporal Dementia Spectrum: A Single-Center Study

Author

Pietro Cortelli, Nicola Mometto, Piero Parchi, Roberto Poda, Federico Oppi, Barbara Polischi, Michelangelo Stanzani-Maserati, Samir Abu-Rumeileh, Rocco Liguori, Anna Bartoletti-Stella, Sabina Capellari, Abu-Rumeileh, Samir, Mometto, Nicola, Bartoletti-Stella, Anna, Polischi, Barbara, Oppi, Federico, Poda, Roberto, Stanzani-Maserati, Michelangelo, Cortelli, Pietro, Liguori, Rocco, Capellari, Sabina, and Parchi, Piero

Subjects
0301 basic medicine, Male, TDP-43, Neuropsychological Tests, Gastroenterology, Primary progressive aphasia, Cohort Studies, 0302 clinical medicine, Cerebrospinal fluid, Neurofilament Proteins, neurofilament light, amyotrophic lateral sclerosi, tau, Amyotrophic lateral sclerosis, parkinsonism, General Neuroscience, Parkinsonism, General Medicine, Frontotemporal lobar degeneration, Alzheimer's disease, Middle Aged, Verbal Learning, Magnetic Resonance Imaging, Psychiatry and Mental health, Clinical Psychology, Frontotemporal Dementia, Biomarker (medicine), Female, Frontotemporal dementia, medicine.medical_specialty, Tomography Scanners, X-Ray Computed, tau Proteins, Progressive supranuclear palsy, 03 medical and health sciences, Alzheimer Disease, Internal medicine, mental disorders, medicine, Humans, Aged, behavioral variant, Neuroscience (all), Amyloid beta-Peptides, business.industry, nutritional and metabolic diseases, corticobasal syndrome, progressive supranuclear palsy, medicine.disease, nervous system diseases, 030104 developmental biology, ROC Curve, primary progressive aphasia, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, Biomarkers
Abstract

Cerebrospinal fluid (CSF) neurofilament light chain protein (NfL) and Alzheimer's disease (AD) core biomarker levels have been evaluated in cohorts of patients with frontotemporal dementia spectrum (FTD), but the distribution of values across the different clinical syndromes and underlying proteinopathies, and the relative diagnostic accuracy appear discordant among studies. We measured CSF NfL, total (t)-tau, phosphorylated (p)-tau, and amyloid-β (Aβ) 42 in healthy controls (n = 38) and subjects with a clinical, genetic, CSF biomarker-based, and/or neuropathological diagnosis of FTD (n = 141) or AD (n = 60). Sub-analyses were conducted in a proportion of subjects with definite and/or probable frontotemporal lobar degeneration with tau (FTLD-TAU) (n = 42) or TDP43 pathology (FTLD-TDP) (n = 36). Both FTD and AD groups showed significantly increased CSF NfL levels in comparison to controls (p < 0.001). CSF NfL levels were significantly higher in FTD patients than in AD (p < 0.001), reaching the highest values in amyotrophic lateral sclerosis associated with FTD. Patients with probable and definite FTLD-TDP had significantly higher NfL levels (p < 0.001) and lower p-tau/t-tau values (p < 0.001) in comparison with probable and definite FTLD-TAU cases. NfL showed good diagnostic accuracy in the distinction between FTD and controls (AUC 0.862±0.027) and yielded an accuracy (AUC 0.861±0.045) comparable to that of the p-tau/t-tau ratio (AUC 0.814±0.050), with 80.0% sensitivity and 81.0% specificity, in the discrimination between probable/definite FTLD-TAU and FTLD-TDP. Our data further validate CSF NfL as a surrogate biomarker of neurodegeneration and disease severity in patients with FTD spectrum. Moreover, they demonstrate a good diagnostic value for NfL and p-tau/t-tau ratio in the discrimination between FTLD-TAU and FTLD-TDP.

Published
2018

15. Mitochondrial dysfunction in myotonic dystrophy type 1

Author

Caterina Tonon, David Neil Manners, Roberto Poda, Federico Oppi, Claudio Bianchini, Laura Ludovica Gramegna, Raffaele Lodi, Stefano Zanigni, Rocco Liguori, Patrizia Avoni, Maria Pia Giannoccaro, Claudia Testa, Stefania Evangelisti, Gramegna, Laura Ludovica, Giannoccaro, Maria Pia, Manners, David Neil, Testa, Claudia, Zanigni, Stefano, Evangelisti, Stefania, Bianchini, Claudio, Oppi, Federico, Poda, Roberto, Avoni, Patrizia, Lodi, Raffaele, Liguori, Rocco, and Tonon, Caterina

Subjects
0301 basic medicine, Adult, Male, medicine.medical_specialty, Mitochondrial Diseases, Proton Magnetic Resonance Spectroscopy, Myotonic dystrophy, Severity of Illness Index, 03 medical and health sciences, Lateral ventricles, Young Adult, 0302 clinical medicine, Adenosine Triphosphate, In vivo, Internal medicine, medicine, Humans, Myotonic Dystrophy, Magnetic resonance imaging (MRI), Muscle, Skeletal, Gene, Pathological, Exercise, Genetics (clinical), Aged, business.industry, Myotonic dystrophy type 1, Skeletal muscle, Brain, Organ Size, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Pathophysiology, In vitro, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Neurology, Lower Extremity, Pediatrics, Perinatology and Child Health, Brain proton MR spectroscopy, Muscle phosphorous MR spectroscopy, Female, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

The pathophysiological mechanism linking the nucleotide expansion in the DMPK gene to the clinical manifestations of myotonic dystrophy type 1 (DM1) is still unclear. In vitro studies demonstrate DMPK involvement in the redox homeostasis of cells and the mitochondrial dysfunction in DM1, but in vivo investigations of oxidative metabolism in skeletal muscle have provided ambiguous results and have never been performed in the brain. Twenty-five DM1 patients (14M, 39 ± 11years) underwent brain proton MR spectroscopy (1H-MRS), and sixteen cases (9M, 40 ± 13 years old) also calf muscle phosphorus MRS (31P-MRS). Findings were compared to those of sex- and age-matched controls. Eight DM1 patients showed pathological increase of brain lactate and, compared to those without, had larger lateral ventricles (p

Published
2018

16. Effects on cognition of 20 days of anodal trans-cranial Direct Current Stimulation (tDCS) over left dorsolateral-pre-frontal cortex (DLPFC) in patients affected by Mild Cognitive Impairment: A case-control study

Author

Giovanni Rizzo, Roberto Poda, Michelangelo Stanzani-Maserati, Sabina Capellari, Rocco Liguori, E. Fileccia, Federico Oppi, and V. Di Stasi

Subjects
medicine.medical_specialty, education.field_of_study, business.industry, Population, Neuropsychology, Stimulation, Cognition, Dorsolateral, Audiology, Sensory Systems, medicine.anatomical_structure, Neurology, Physiology (medical), Cortex (anatomy), Medicine, Neurology (clinical), Analysis of variance, business, education, Episodic memory
Abstract

Mild Cognitive impairment (MCI) affects as long as 15% of population in the elderly. Trans-cranial direct current stimulation (tDCS) is a non invasive technique of neuro-modulation which has proved to influence performances on different cognitive domains. We investigate effects on cognition of 20 days anodal tDCS in 17 MCI patients compared to 17 matched MCI patients. Patients underwent neuropsychological evaluation at baseline and then were randomly assigned to anodal or sham group. tDCS protocol consisted in 20 min, 5 days per week (up to total 20 days), 2 mA anodal stimulation over left dorsolateral pre-frontal cortex (DLPFC). At the end of the last day of stimulation a second neuropsychological evaluation was performed. We compared baseline and after stimulation neuropsychological results in anodal vs sham groups using repeated ANOVA measures as statistical analysis test. At follow-up anodal group showed improvement in verbal episodic memory (p

Published
2019

17. The Tree-Drawing Test (Koch’s Baum Test): A Useful Aid to Diagnose Cognitive Impairment

Author

Roberto Poda, Roberto Gallassi, Federico Oppi, Luisa Sambati, Maddalena De Matteis, Michelangelo Stanzani Maserati, and Corrado Matacena

Subjects
Male, Gerontology, Pediatrics, medicine.medical_specialty, Article Subject, Neurosciences. Biological psychiatry. Neuropsychiatry, Neuropsychological Tests, Baum test, Pick Disease of the Brain, Alzheimer Disease, Task Performance and Analysis, mental disorders, medicine, Humans, Dementia, Cognitive Dysfunction, Cognitive impairment, Vascular dementia, Aged, Aged, 80 and over, Dementia, Vascular, Cognition, General Medicine, Middle Aged, medicine.disease, Test (assessment), Neuropsychology and Physiological Psychology, Neurology, Frontotemporal Dementia, Female, Neurology (clinical), Alzheimer's disease, Psychology, RC321-571, Research Article, Frontotemporal dementia
Abstract

Objective. To study the Tree-Drawing Test in a group of demented patients and compare it with a group of mild cognitively impaired patients (MCI) and controls.Methods. Consecutive outpatients were classified as affected by dementia (Alzheimer’s disease (AD), frontotemporal dementia (FTD), and vascular dementia (VD)) or by MCI. Patients and controls underwent the Tree-Drawing Test and MMSE.Results. 118 AD, 19 FTD, 46 VD, and 132 MCI patients and 90 controls were enrolled. AD patients draw trees globally smaller than other patients and controls. FTD patients draw trees with a wider space occupation than AD and MCI patients but smaller than controls as well as VD patients. Trees drawn by MCI patients are intermediate in size between AD patients and controls. The trunk-to-crown ratio of trees drawn by cognitive impaired patients is greater than controls while the tree size-relative-to-page space index is significantly smaller. The tree size-relative-to-page space index of trees drawn by AD patients is smaller than that of the other cognitively impaired patients. Tree height and the trunk-to-crown ratio are independent predictors of cognitive impairment.Conclusions. Trees drawn by cognitively impaired patients are different from those drawn by healthy subjects with a progressive differentiation from mild to more relevant degrees of cognitive impairment.

Published
2015

18. Profile of neuropsychological impairment in Sleep-related Hypermotor Epilepsy

Author

Federica Provini, Laura Licchetta, Tommaso Pippucci, Barbara Mostacci, Francesca Bisulli, Sara Baldassari, Paolo Tinuper, Roberto Poda, Corrado Zenesini, Luca Vignatelli, Veronica Menghi, Licchetta, Laura, Poda, Roberto, Vignatelli, Luca, Pippucci, Tommaso, Zenesini, Corrado, Menghi, Veronica, Mostacci, Barbara, Baldassari, Sara, Provini, Federica, Tinuper, Paolo, and Bisulli, Francesca

Subjects
0301 basic medicine, Adult, Male, medicine.medical_specialty, Wilcoxon signed-rank test, Cross-sectional study, Epilepsy, Frontal Lobe, Intelligence, Audiology, Electroencephalography, Neuropsychological Tests, Affect (psychology), 03 medical and health sciences, symbols.namesake, Epilepsy, 0302 clinical medicine, Genetic, Neuropsychology, Seizures, medicine, Humans, Fisher's exact test, medicine.diagnostic_test, business.industry, Medicine (all), General Medicine, Nocturnal frontal lobe epilepsy, medicine.disease, Test (assessment), 030104 developmental biology, Cross-Sectional Studies, Extra-frontal deficit, symbols, Anticonvulsants, Female, business, Executive functioning, Cognition Disorders, Sleep, 030217 neurology & neurosurgery
Abstract

Objective: The aim of this study was to characterize the neuropsychological features of a representative sample of Sleep-related Hypermotor Epilepsy (SHE) patients and to highlight clinical associations. Methods: This cross-sectional study included 60 consecutive patients with video/video-electroencephalography–documented SHE. All were assessed by measures of intelligence. Individuals with normal scores underwent a standardized battery of tests. The Fisher exact test and Wilcoxon rank-sum test for statistical analysis. Results: Mean total IQ was 96.96 ± 21.50, with significant differences between verbal and performance scores (p < 0.0001). Nine patients (15%) had intellectual disability (ID)/cognitive deterioration. Of the 49 assessed by the extensive battery, 23 (46.9%) showed deficits in at least one test evaluating phonemic fluency (24.5%), memory (24.5%), inhibitory control (22.4%), or working memory (10.2%). Patients with mutations in SHE genes had lower IQ than patients without mutations, irrespective of the specific gene (p = 0.0176). Similarly, pathological neurological examination (NE) and “any underlying brain disorder” (at least one among pathological NE, abnormal brain magnetic resonance imaging findings, perinatal insult) were associated with ID (p = 0.029, p = 0.036). A higher seizure frequency at last assessment and poor prognosis correlated with worse scores in visuo-spatial memory (p = 0.038, p = 0.040) and visuo-spatial abilities (p = 0.016). Status epilepticus (p = 0.035), poor response to antiepileptic drugs (p = 0.033), and poor prognosis (p = 0.020) correlated with lower shifting abilities, whereas bilateral convulsive seizures correlated with worse working memory (p = 0.049). Conclusion: In all, 53.3% of SHE patients had neuropsychological deficits. The profile of impairment showed worse verbal IQ, as well as deficits in extrafrontal and selective frontal functions. Our data support the contribution of genetics in ID by different biological mechanisms. Variables of clinical severity affect memory and executive functioning.

Published
2017

19. Contents Vol. 72, 2014

Author

Satz Mengensatzproduktion, Julie Haesebaert, Corinne Feutrier, Seung Hyup Hyun, Kazutaka Nishina, Norbert Nighoghossian, Murat Kürtüncü, Markus Schwaninger, Roland Veltkamp, Emmanuel Coudeyre, Gerd U. Auffarth, Vittorio Di Piero, Kyung-Han Lee, Michelangelo Stanzani-Maserati, Marcel Arnold, Socrates J. Tzartos, Julio Lama, Pietro Cortelli, Jong-Soo Kim, Sadegh Izadi, Salmo Raskin, Tae Ok Son, Francesca Puledda, Takahiro Kondo, Adriana Moro, Jacques Luauté, Caspar Brekenfeld, Arzu Çoban, Anne Koy, Maurizio Paciaroni, Masatoyo Nishizawa, Pia Flossdorf, Michael Chopp, John Tzartos, Marwan El-Koussy, Eckhard Schönau, Evelyne Decullier, Massimiliano Toscano, Maryam Sharifian, Luisa Sambati, Laurent Derex, Druckerei Stückle, Maria Alessandria, Lars Timmermann, Mohammad Maarouf, Renato P. Munhoz, Mariana Moscovich, Thomas Liebig, Recai Turkoglu, Gilles Rode, Patrick Ffrench, Yves Berthezène, Erkingül Shugaiv, Dirk M. Hermann, Alessandro Viganò, K. Amande M. Pauls, Je Young Yeon, Izumi Kawachi, Christos Stergiou, Masami Tanaka, Audrey Janoly-Dumenil, Julien Berthiller, Stephanie Bauler, Gian Luigi Lenzi, Alireza Nikseresht, Thomas Ritzenthaler, Can Ebru Bekircan-Kurt, Mauricio Zambrano, Jan C. Purrucker, Mohammad Ali Sahraian, Edoardo Vicenzini, Masahiro Abo, Takanori Yokota, Johannes Becker, Roberto Gallassi, Federico Oppi, In-Seok Park, Suk Jae Kim, Erdem Tüzün, Sophie Jacquin-Courtois, Ahmed Farghali, Anne-Marie Schott, Marie-France Weiner, Paraskevi Zisimopoulou, Pyoung Jeon, Monica Acciarresi, Ersin Tan, Oliver Fricke, Keon Ha Kim, Walter O. Arruda, Esme Ekizoglu, Tom Bruckner, Rana Karabudak, Michel Hanss, Giulio Guidetti, Hélio A.G. Teive, Aslı Tuncer Kurne, Tamako Misawa, Andrea O. Rossetti, Julien Bogousslavsky, Hyun-Ji Cho, Keiko Tanaka, John Russell Silver, Sevim Erdem-Ozdamar, Markus Zorn, Frank W. Stahnisch, Naoki Yamada, Jung-Seok Kim, Federica Provini, Sugao Mitani, Seung-Chyul Hong, Betül Baykan, Kwang-Soo Lee, Oh Young Bang, Masoud Etemadifar, Hyung Jin Shin, Zahra Nasr, Roberto Poda, Laura Mechtouff, Gerhard Schroth, Teruhiko Sekiguchi, Oliver Herrmann, Benoit Allenet, Hidehiro Mizusawa, Masato Shimizu, Julia K. Lutsch, Giovanna Calandra-Buonaura, Victor J. Del Brutto, Miho Akaza, In-Uk Song, Gereon R. Fink, Oscar H. Del Brutto, Umut Kalyoncu, Wataru Kakuda, and Tae-Hee Cho

Subjects
Neurology, Neurology (clinical)
Published
2014

20. Simple verbal analogies test: normative data on a short task exploring abstract thinking

Author

Roberto Poda, Michelangelo Stanzani Maserati, Federico Oppi, Roberto Gallassi, Maddalena De Matteis, Luisa Sambati, and Gianfranco Marano

Subjects
Adult, Aged, 80 and over, Male, Aging, California Verbal Learning Test, Verbal Behavior, Working memory, Neuropsychology, Middle Aged, Neuropsychological Tests, Executive functions, Developmental psychology, Thinking, Memory, Short-Term, Humans, Raw score, Semantic memory, Normative, Female, Geriatrics and Gerontology, Verbal memory, Cognition Disorders, Psychology, Aged, Cognitive psychology
Abstract

The simple verbal analogies test (SVAT) is a short neuropsychological task requiring few minutes of administration that explores inductive verbal abstract thinking. It already showed a good specificity and sensitivity in discriminating normal controls from probable Alzheimer’s disease patients. Verbal working memory, semantic knowledge and memory and word-finding ability are also involved in performing analogies. The aim of this study is to provide the normative values of this test in a sample of normal controls and corrections of raw scores and equivalent scores. We determined the normative values of SVAT in a sample of 424 normal controls to provide corrections of raw scores and equivalent scores. SVAT is a useful test to assess executive functions, working memory and to discriminate between cognitive deterioration and normal aging.

Published
2013

21. Precuneal Thickness and Depression in Parkinson Disease

Author

Luisa Sambati, David Neil Manners, Giovanna Calandra-Buonaura, Roberto Poda, Stefania Evangelisti, Claudia Testa, Rossana Terlizzi, Caterina Tonon, Federico Oppi, Pietro Cortelli, Raffaele Lodi, Stefano Zanigni, Zanigni, Stefano, Sambati, Luisa, Evangelisti, Stefania, Testa, Claudia, Calandra-Buonaura, Giovanna, Manners, David Neil, Terlizzi, Rossana, Poda, Roberto, Oppi, Federico, Lodi, Raffaele, Cortelli, Pietro, and Tonon, Caterina

Subjects
0301 basic medicine, Adult, Male, medicine.medical_specialty, Neurology, Precuneus, Precuneu, Disease, 03 medical and health sciences, 0302 clinical medicine, Text mining, Physical medicine and rehabilitation, Parietal Lobe, Medicine, Humans, skin and connective tissue diseases, Aged, Cortical thickne, Cerebral Cortex, medicine.diagnostic_test, business.industry, Depression, Magnetic resonance imaging, Parkinson Disease, Middle Aged, Magnetic Resonance Imaging, 030104 developmental biology, medicine.anatomical_structure, Female, sense organs, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Background: Depression-related gray matter changes in Parkinson disease (PD) patients have been reported, although studies investigating cortical thickness in early-stage disease are lacking. Objective: We aimed to evaluate cortical changes related to depression in early-stage PD patients with an extensive neuropsychological evaluation. Methods: 17 PD patients and 22 healthy controls underwent a 1.5-T brain MR protocol, and voxel-wise differences in cortical thickness among patients with (n = 6) and without (n = 11) depression and controls were evaluated using FreeSurfer software. Results: Cortical thickness was increased in the precuneus bilaterally in PD patients with depression compared to the other groups (number of vertices >100; p < 0.001, uncorrected) with a direct correlation with the Beck Depression Inventory score (p < 0.001, uncorrected). Conclusion: Precuneal cortical thickening is evident in PD patients with mild-moderate depression even in the early stages of the disease. This finding may reflect the early involvement of this region in the development of PD-related depression.

Published
2016

22. Slowly progressive aphemia: a neuropsychological, conventional, and functional MRI study

Author

Raffaele Lodi, Raffaele Agati, M. Stanzani Maserati, Luisa Sambati, Daniela Cevolani, Roberto Gallassi, Roberto Poda, Federico Oppi, Gallassi R, Sambati L, Poda R, Oppi F, Stanzani Maserati M, Cevolani D, Agati R, and Lodi R.

Subjects
Male, medicine.medical_specialty, Neurology, Apraxias, APRAXIA OF SPEECH, Dermatology, Degeneration (medical), Neuropsychological Tests, Audiology, Dysarthria, Image Processing, Computer-Assisted, medicine, Humans, Longitudinal Studies, Aged, Language Tests, Neuropsychology, Brain, General Medicine, FRONTOTEMPORAL DEMENTIA, medicine.disease, Magnetic Resonance Imaging, Oxygen, APHEMIA, Psychiatry and Mental health, Frontal lobe, Dysprosody, Disease Progression, Neurology (clinical), PRIMARY MOTOR APHASIA, medicine.symptom, Mental Status Schedule, Articulation (phonetics), Psychology, DYSARTHRIA, Frontotemporal dementia
Abstract

Slowly progressive aphemia (SPA) is a rare focal degenerative disorder characterized by severe dysarthria, frequent orofacial apraxia, dysprosody, phonetic and phonemic errors without global cognitive deterioration for many years. This condition is caused by a degeneration of anterior frontal lobe regions, mainly of the left frontal operculum. We report a case of SPA with a course of 8 years, evaluated by repeated neuropsychological, conventional, and functional MRI examinations. In our case, neuropsychological examinations showed a progressive impairment of speech articulation including dysprosody, phonetic and phonemic errors, and slight writing errors. No global cognitive deterioration was detected and the patient is still completely autonomous. Morphological and functional investigations showed, respectively, a progressive atrophy and progressive impairment of the left frontal region, confirming the role of the opercular region in determining this rare syndrome. During verbal task generation as the cortical activation of this region gradually decreased, the language articulation worsened.

Published
2011

23. Are subjective cognitive complaints a risk factor for dementia?

Author

Roberto Poda, Gianfranco Marano, Michelangelo Stanzani Maserati, Roberto Gallassi, Luisa Sambati, Simona Scortichini, Federico Oppi, Gallassi R, Oppi F, Poda R, Scortichini S, Stanzani Maserati M, Marano G, and Sambati L.

Subjects
Male, MILD COGNITIVE IMPAIRMENT, medicine.medical_specialty, Time Factors, Neurology, Dermatology, behavioral disciplines and activities, Risk Factors, Internal medicine, mental disorders, medicine, Humans, Dementia, Apathy, Prospective Studies, Risk factor, Prospective cohort study, Psychiatry, Aged, NEUROPSYCHOLOGICAL TESTS, MEMORY, SUBJECTIVE COGNITIVE COMPLAINTS, Lupus Vasculitis, Central Nervous System, Cognition, General Medicine, Middle Aged, Prognosis, medicine.disease, Psychiatry and Mental health, Case-Control Studies, Disease Progression, Female, Neurology (clinical), Neurosurgery, medicine.symptom, Verbal memory, Cognition Disorders, Psychology, Follow-Up Studies
Abstract

The objective is to evaluate the prognosis of subjective cognitive complaints (SCC) patients during 4-year follow-up. A prospective study on 92 SCC patients investigating their cognitive, affective and behavioural aspects. SCC patients were classified as having no objective cognitive impairment (NOCI), mild cognitive impairment (MCI), or subtypes of MCI. RESULTS: 43 patients were found to have NOCI and 49 MCI. During the follow-up, 45.5% of NOCI patients remained unchanged, 13.9% were diagnosed as MCI and only one progressed to dementia. Of the MCI patients, 32.3% remained stable, 18.4% became demented and 4% reverted to NOCI. Visual attention, behavioural memory, long-term verbal memory, apathy and caregiver distress, provided independent predictors of progression to dementia.

Published
2010

24. Subjective cognitive complaints, neuropsychological performance, affective and behavioural symptoms in non-demented patients

Author

Roberto Poda, Federico Oppi, Antonietta Bisulli, Roberto Gallassi, Carla Di Felice, R. Gallassi, A. Bisulli, F. Oppi, R. Poda, and C. Di Felice

Subjects
Male, NEUROPSYCHOLOGICAL TEST, Psychometrics, MEMORY TESTING, Neuropsychological Tests, Irritability, BEHAVIOURAL DISTURBANCES, Risk Factors, medicine, Humans, Dementia, Neuropsychological assessment, Aged, Psychiatric Status Rating Scales, Memory Disorders, medicine.diagnostic_test, Depression, Mood Disorders, MEMORY, Cognitive disorder, Age Factors, Neuropsychology, Social Behavior Disorders, Cognition, Neuropsychological test, Middle Aged, COGNITIVE IMPAIRMENT, medicine.disease, Psychiatry and Mental health, Educational Status, Anxiety, Female, Geriatrics and Gerontology, medicine.symptom, Cognition Disorders, Psychology, Clinical psychology
Abstract

Objective Subjective cognitive complaints (SCC) have been previously investigated to establish whether they are risk factors for dementia, but no clear-cut conclusions have emerged. In this study non-demented patients with SCC were studied and the neuropsychological findings, affective and behavioural aspects and parameters with the highest correct classifications in discriminating patients who had only SCC but no objective clinical and neuropsychological impairment, i.e. no cognitive impairment (NCI) patients and those with objective neuropsychological deficits, namely patients with mild cognitive (MCI) were analyzed. Methods Consecutive non-demented outpatients with SCC were enrolled of over 9 months and examined using neuropsychological tests and scales for depression, anxiety and behaviour. Clinical criteria and neuropsychological test results were used to classify patients into groups of NCI, MCI and subtypes of MCI. Results Ninety-two patients with SCC were included; 49 of them had objective deficits (MCI patients), whereas 43 were without any clinical and cognitive impairment (NCI patients). These patients had lower age, higher education and better general cognitive indices than MCI patients who had higher caregiver distress, depression and irritability. The combination of a battery for mental deterioration and for behavioural memory assessment were the most discriminative in differentiating the two groups. Conclusions An objective cognitive impairment, reaching the criteria for a MCI diagnosis, was present in almost half of patients having SCC. MCI patients have more behavioural disturbances than NCI subjects. SCC should not be underestimated and appropriate neuropsychological assessment is required to reassure subjects with normal results and to identify patients with MCI. Copyright © 2007 John Wiley & Sons, Ltd.

Published
2007

25. Letter re: Effects of orthostatic hypotension on cognition in Parkinson disease

Author

Luisa Sambati, Pietro Guaraldi, Roberto Gallassi, Pietro Cortelli, Roberto Poda, Giovanna Calandra-Buonaura, Laura Solieri, Guaraldi, Pietro, Poda, Roberto, Calandra-Buonaura, Giovanna, Solieri, Laura, Sambati, Luisa, Gallassi, Roberto, and Cortelli, Pietro

Subjects
medicine.medical_specialty, business.industry, Cognition, Disease, orthostatic hypotension, Parkinson disease, Hypotension, Orthostatic, 03 medical and health sciences, Orthostatic vital signs, 0302 clinical medicine, Internal medicine, Cardiology, Humans, Medicine, Cognitive Dysfunction, 030212 general & internal medicine, Neurology (clinical), business, Cognitive impairment, 030217 neurology & neurosurgery
Abstract

We read with interest the article by Centi et al.,1 which investigated the relation between orthostatic hypotension (OH) and posture-mediated cognitive impairment in 18 patients with idiopathic Parkinson disease (PD) with OH (PDOH) and 19 patients with PD without OH and 18 controls.1 The authors demonstrated that, during upright posture, PDOH exhibited a transient wider range of deficits in executive function, memory, and visuospatial function in excess of those found in PD without OH.

Published
2017

26. Cognitive and sleep features of multiple system atrophy: review and prospective study

Author

Federico Oppi, Roberto Poda, Federica Provini, Roberto Gallassi, Maria Alessandria, Luisa Sambati, Michelangelo Stanzani-Maserati, Giovanna Calandra-Buonaura, Pietro Cortelli, Stanzani-Maserati, Michelangelo, Gallassi, Roberto, Calandra-Buonaura, Giovanna, Alessandria, Maria, Oppi, Federico, Poda, Roberto, Sambati, Luisa, Provini, Federica, and Cortelli, Pietro

Subjects
Male, medicine.medical_specialty, Longitudinal Studie, Audiology, Cognitive neuroscience, REM sleep behavior disorder, Atrophy, Cognition, mental disorders, medicine, Humans, Dementia, Longitudinal Studies, Prospective Studies, Effects of sleep deprivation on cognitive performance, Psychiatry, Neuropsychology, Middle Aged, Multiple System Atrophy, Executive functions, medicine.disease, nervous system diseases, Prospective Studie, Neurology, Female, Neurology (clinical), Psychology, Sleep, Human
Abstract

Background: The profile and degree of cognitive impairment in Multiple System Atrophy (MSA) and the impact of sleep disorders, REM sleep behavior disorder (RBD) in particular, in parkinsonism-related cognitive deficits are currently being debated. Summary: We reviewed the cognitive, affective and sleep findings in MSA and also carried out a longitudinal investigation of 10 MSA patients. At the first evaluation, 3 patients showed isolated cognitive deficits. After a mean of 16 months, these patients remained unchanged, while 1 patient worsened from a normal condition. No significant differences emerged when the cognitive, affective and video-polysomnographic findings of MSA-P and MSA-C were compared. Depression was present in half of the patients, although it did not influence their cognitive performance. Comparisons between the first and second evaluation data showed significant worsening in visual attention and in ADL/IADL and UMSARS. Key Messages: Isolated cognitive deficits are evidenced in a minority of MSA patients with the absence of a clear-cut diagnosis of dementia in the early stages of the disease. Attention and executive functions are often impaired. This study with a short follow-up period showed that RBD, although present in almost all patients affected by MSA, does not appear a clear early marker of cognitive impairment. Future longer-term studies with a larger patient sample are thus encouraged.

Published
2014

27. Accelerated long-term forgetting in temporal lobe epilepsy: Evidence of improvement after left temporal pole lobectomy

Author

Luisa Sambati, Roberto Poda, Federico Oppi, Roberto Gallassi, Michelangelo Stanzani Maserati, Paolo Tinuper, Marco Giulioni, Gallassi R, Sambati L, Poda R, Stanzani Maserati M, Oppi F, Giulioni M, and Tinuper P

Subjects
Male, Amnesia, Hippocampal formation, Neuropsychological Tests, Amygdala, Functional Laterality, Temporal lobe, NEUROPSYCHOLOGY, Behavioral Neuroscience, Epilepsy, TEMPORAL POLE LOBECTOMY, medicine, Humans, COGNITIVE FUNCTIONS, Memory Disorders, Forgetting, digestive, oral, and skin physiology, Middle Aged, medicine.disease, Anterior Temporal Lobectomy, Uncus, medicine.anatomical_structure, ACCELERATED LONG-TERM FORGETTING, Neurology, Epilepsy, Temporal Lobe, Memory consolidation, Female, TEMPORAL LOBE EPILEPSY, Neurology (clinical), medicine.symptom, Psychology, Neuroscience
Abstract

Accelerated long term forgetting (ALF) is a characteristic cognitive aspect in patients affected by temporal lobe epilepsy that is probably due to an impairment of memory consolidation and retrieval caused by epileptic activity in hippocampal and parahippocampal regions. We describe a case of a patient with TLE who showed improvement in ALF and in remote memory impairment after an anterior left temporal pole lobectomy including the uncus and amygdala. Our findings confirm that impairment of hippocampal functioning leads to pathological ALF, whereas restoration of hippocampal functioning brings ALF to a level comparable to that of controls.

Published
2011

28. Definition of the neurological phenotype associated with dup (X) (p11.22-p11.23)

Author

Corrado Romano, Roberto Giorda, Girolamo Aurelio Vitello, Maria Savio, Massimo Mastrangelo, M. Broli, Roberto Poda, B. Bernardi, Francesca Bisulli, Santina Reitano, Roberto Gallassi, Marco Seri, Orsetta Zuffardi, Isabella Fiocchi, Claudio Zucca, Paolo Tinuper, Elena Fontana, Sebastiano A. Musumeci, Maria Clara Bonaglia, Daniela Cevolani, Bernardo Dalla Bernardina, Raffaele Agati, Serafino Buono, Broli M., Bisulli F., Mastrangelo M., Fontana E., Fiocchi I., Zucca C., Bonaglia M.C., Buono S., Musumeci S.A., Romano C., Reitano S., Savio M., Vitello G.A., Bernardi B., Cevolani D., Agati R., Poda R., Gallassi R., Giorda R., Zuffardi O., Bernardina B.D., Seri M., and Tinuper P.

Subjects
Adult, Male, Xp11.2211.23, medicine.medical_specialty, Pediatrics, Neurology, Adolescent, Gene Dosage, Neural Conduction, speech impairment, Neurological examination, Status epilepticus, Electroencephalography, Neuropsychological Tests, mental retardation, Gene Duplication, Intellectual Disability, medicine, Humans, Neuropsychological assessment, Child, In Situ Hybridization, Fluorescence, Chromosomes, Human, X, medicine.diagnostic_test, Electrodiagnosis, Neuropsychology, Brain, Magnetic resonance imaging, General Medicine, Magnetic Resonance Imaging, Phenotype, Speech delay, Female, Neurology (clinical), medicine.symptom, Nervous System Diseases, Psychology, Neuroscience
Abstract

The aim of this study was to describe in detail the neurological features of nine patients carrying the recently reported microduplication at Xp11.22-11.23. Clinical and neurological examination, brain magnetic resonance imaging (except for two patients), electroencephalography and a neuropsychological assessment specific for language disturbances were performed in nine patients with microduplication at Xp11.22-11.23, disclosed by comparative genomic hybridisation array. Six patients were familial cases belonging to three unrelated pedigrees and three were sporadic cases. The patients had the following characteristics: mild dysmorphic facial features (except for two patients), mental retardation with moderate to severe global language deterioration, electroencephalographic epileptiform discharges during wakefulness and especially during sleep or electrical status epilepticus during slow sleep in younger cases, and negative brain magnetic resonance imaging. The main clinical features of this new microduplication syndrome were mild facial dysmorphisms, from increased electroencephalogram abnormalities during sleep to electrical status epilepticus during slow sleep, and mental retardation mainly involving language function in the absence of detectable brain lesions. In the absence of detectable brain lesions, speech delay may be associated with electrical status epilepticus during slow sleep or, alternatively, related to abnormal brain expression of a dosage-sensitive gene contained within the duplication region.

Published
2011

29. Progression of cognitive impairment in parkinsonian patients

Author

Roberto Poda, Giovanna Calandra-Buonaura, Luisa Sambati, M. Stanzani Maserati, Federico Oppi, Pietro Cortelli, and Roberto Gallassi

Subjects
medicine.medical_specialty, Physical medicine and rehabilitation, Neurology, business.industry, Medicine, Neurology (clinical), business, Cognitive impairment
Published
2013

30. Speech apraxia or aphemia?

Author

Roberto Poda, Roberto Gallassi, Federico Oppi, Michelangelo Stanzani Maserati, R. Gallassi, R. Poda, M. Stanzani Maserati, and F. Oppi

Subjects
medicine.medical_specialty, business.industry, Audiology, medicine.disease, Aphasia, Primary Progressive, Aphasia PPA, Neurology, Frontotemporal Dementia, Aphasia, Speech apraxia, Medicine, Neurology (clinical), medicine.symptom, business, Frontotemporal dementia
Published
2009

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