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1. Metabolic network alterations as a supportive biomarker in dementia with Lewy bodies with preserved dopamine transmission

Author

Stockbauer, Anna, Beyer, Leonie, Huber, Maria, Kreuzer, Annika, Palleis, Carla, Katzdobler, Sabrina, Rauchmann, Boris-Stephan, Morbelli, Silvia, Chincarini, Andrea, Bruffaerts, Rose, Vandenberghe, Rik, Kramberger, Milica G., Trost, Maja, Garibotto, Valentina, Nicastro, Nicolas, Lathuilière, Aurélien, Lemstra, Afina W., van Berckel, Bart N. M., Pilotto, Andrea, Padovani, Alessandro, Ochoa-Figueroa, Miguel A., Davidsson, Anette, Camacho, Valle, Peira, Enrico, Bauckneht, Matteo, Pardini, Matteo, Sambuceti, Gianmario, Aarsland, Dag, Nobili, Flavio, Gross, Mattes, Vöglein, Jonathan, Perneczky, Robert, Pogarell, Oliver, Buerger, Katharina, Franzmeier, Nicolai, Danek, Adrian, Levin, Johannes, Höglinger, Günter U., Bartenstein, Peter, Cumming, Paul, Rominger, Axel, and Brendel, Matthias

Published
2024
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5. Neuroimaging Findings in Mild Cognitive Impairment

Author

Massa, Federico, Bauckneht, Matteo, Peira, Enrico, Lapucci, Caterina, Picco, Agnese, Capitanio, Selene, Arnaldi, Dario, Roccatagliata, Luca, Chincarini, Andrea, Nobili, Flavio, Dierckx, Rudi A. J. O., editor, Otte, Andreas, editor, de Vries, Erik F. J., editor, van Waarde, Aren, editor, and Leenders, Klaus L., editor

Published
2021
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6. Limbic Network Derangement Mediates Unawareness of Apathy in Mild Cognitive Impairment due to Alzheimer's Disease: Clues from [18F]FDG PET Voxel-Wise Analysis.

Author

Kreshpa, Wendy, Raffa, Stefano, Girtler, Nicola, Brugnolo, Andrea, Mattioli, Pietro, Orso, Beatrice, Calizzano, Francesco, Arnaldi, Dario, Peira, Enrico, Chincarini, Andrea, Tagliafico, Luca, Monacelli, Fiammetta, Calcagno, Pietro, Serafini, Gianluca, Gotta, Fabio, Mandich, Paola, Pretta, Stefano, Del Sette, Massimo, Sofia, Luca, and Sambuceti, Gianmario

Subjects
MILD cognitive impairment, ALZHEIMER'S disease, CINGULATE cortex, BRAIN metabolism, CAREGIVERS
Abstract

Background: Discrepancy between caregiver and patient assessments of apathy in mild cognitive impairment (MCI) is considered an index of apathy unawareness, independently predicting progression to AD dementia. However, its neural underpinning are uninvestigated. Objective: To explore the [18F]FDG PET-based metabolic correlates of apathy unawareness measured through the discrepancy between caregiver and patient self-report, in patients diagnosed with MCI. Methods: We retrospectively studied 28 patients with an intermediate or high likelihood of MCI-AD, progressed to dementia over an average of two years, whose degree of apathy was evaluated by means of the Apathy Evaluation Scale (AES) for both patients (PT-AES) and caregivers (CG-AES). Voxel-based analysis at baseline was used to obtain distinct volumes of interest (VOIs) correlated with PT-AES, CG-AES, or their absolute difference (DISCR-AES). The resulting DISCR-AES VOI count densities were used as covariates in an inter-regional correlation analysis (IRCA) in MCI-AD patients and a group of matched healthy controls (HC). Results: DISCR-AES negatively correlated with metabolism in bilateral parahippocampal gyrus, posterior cingulate cortex, and thalamus, PT-AES score with frontal and anterior cingulate areas, while there was no significant correlation between CG-AES and brain metabolism. IRCA revealed that MCI-AD patients exhibited reduced metabolic/functional correlations of the DISCR-AES VOI with the right cingulate gyrus and its anterior projections compared to HC. Conclusions: Apathy unawareness entails early disruption of the limbic circuitry rather than the classical frontal-subcortical pathways typically associated with apathy. This reaffirms apathy unawareness as an early and independent measure in MCI-AD, marked by distinct pathophysiological alterations. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Sex differences in neuroimaging biomarkers in healthy subjects and dementia

Author

Massa, Federico, primary, Arnaldi, Dario, additional, Balma, Michele, additional, Bauckneht, Matteo, additional, Chincarini, Andrea, additional, Ferraro, Pilar M., additional, Grazzini, Matteo, additional, Lapucci, Caterina, additional, Meli, Riccardo, additional, Morbelli, Silvia, additional, Pardini, Matteo, additional, Peira, Enrico, additional, Raffa, Stefano, additional, Roccatagliata, Luca, additional, and Nobili, Flavio, additional

Published
2021
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10. Contributors

Author

Abdelnour, Carla, primary, Abela, Angela, additional, Arnaldi, Dario, additional, Au, Rhoda, additional, Balma, Michele, additional, Barbarino, Paola, additional, Barbera, Mariagnese, additional, Bauckneht, Matteo, additional, Bilbo, Staci D., additional, Biskup, Ewelina, additional, Campbell, Stephen, additional, Chadha, Antonella Santuccione, additional, Chincarini, Andrea, additional, Delage, Charlotte, additional, Dimech, Annemarie Schumacher, additional, Diviani, Nicola, additional, Downie, Sue, additional, Esteban, Ester, additional, Ferraro, Pilar M., additional, Ferretti, Maria Teresa, additional, Foldi, Nancy S., additional, Galea, Liisa A.M., additional, Gammada, Emnet Z., additional, Grazzini, Matteo, additional, Håkansson, Krister, additional, Hill-Strathy, MaryJane, additional, Ilinca, Stefania, additional, Ippati, Stefania, additional, Matthias Ittner, Lars, additional, Jordan, Valeria, additional, Diana Ke, Yazi, additional, Kivipelto, Miia, additional, Lapucci, Caterina, additional, Lee, Bonnie H., additional, Lehtisalo, Jenni, additional, Lorenz-Dant, Klara, additional, Lynch, Chris, additional, Malacon, Karen E., additional, Martinkova, Julie N., additional, Massa, Federico, additional, Meli, Riccardo, additional, Mellino, Simona, additional, Mielke, Michelle M., additional, Mittelman, Mary, additional, Morbelli, Silvia, additional, Nasta, Beatrice, additional, Nobili, Flavio, additional, Pardini, Matteo, additional, Peira, Enrico, additional, Phillips, Susan, additional, Puri, Tanvi A., additional, Raffa, Stefano, additional, Rauen, Katrin, additional, Rendina, Danielle N., additional, Roccatagliata, Luca, additional, Rosenberg, Anna, additional, Rosende-Roca, Maitee, additional, Rovira, Mercè Boada, additional, Rubinelli, Sara, additional, Scerri, Anthony, additional, Scerri, Charles, additional, Sindi, Shireen, additional, Stephen, Ruth, additional, Suzuki, Elina, additional, Szoeke, Cassandra, additional, Toopchiani, Sima, additional, Tremblay, Marie-Ève, additional, Udeh-Momoh, Chinedu, additional, and Weidner, Wendy, additional

Published
2021
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11. Monoaminergic Disfunctions and Misfolded Proteins levels in the Alzheimer’s Disease Continuum

Author

Orso, Beatrice, primary, Peira, Enrico, additional, Arnaldi, Dario, additional, Girtler, Nicola, additional, Brugnolo, Andrea, additional, Mattioli, Pietro, additional, Biassoni, Erica, additional, Donniaquio, Andrea, additional, Massa, Federico, additional, Uccelli, Antonio, additional, Bauckneht, Matteo, additional, Morbelli, Silvia, additional, and Pardini, Matteo, additional

Published
2023
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12. Metabolic network alterations as a supportive biomarker in dementia with Lewy bodies with preserved dopamine transmission

Author

Stockbauer, Anna, primary, Beyer, Leonie, additional, Huber, Maria, additional, Kreuzer, Annika, additional, Palleis, Carla, additional, Katzdobler, Sabrina, additional, Rauchmann, Boris-Stephan, additional, Morbelli, Silvia, additional, Chincarini, Andrea, additional, Bruffaerts, Rose, additional, Vandenberghe, Rik, additional, Kramberger, Milica G., additional, Trost, Maja, additional, Garibotto, Valentina, additional, Nicastro, Nicolas, additional, Lathuilière, Aurélien, additional, Lemstra, Afina W., additional, van Berckel, Bart N. M., additional, Pilotto, Andrea, additional, Padovani, Alessandro, additional, Ochoa-Figueroa, Miguel A., additional, Davidsson, Anette, additional, Camacho, Valle, additional, Peira, Enrico, additional, Bauckneht, Matteo, additional, Pardini, Matteo, additional, Sambuceti, Gianmario, additional, Aarsland, Dag, additional, Nobili, Flavio, additional, Gross, Mattes, additional, Vöglein, Jonathan, additional, Perneczky, Robert, additional, Pogarell, Oliver, additional, Buerger, Katharina, additional, Franzmeier, Nicolai, additional, Danek, Adrian, additional, Levin, Johannes, additional, Höglinger, Günter U., additional, Bartenstein, Peter, additional, Cumming, Paul, additional, Rominger, Axel, additional, and Brendel, Matthias, additional

Published
2023
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13. Neuroimaging Findings in Mild Cognitive Impairment

Author

Massa, Federico, primary, Bauckneht, Matteo, additional, Peira, Enrico, additional, Lapucci, Caterina, additional, Picco, Agnese, additional, Capitanio, Selene, additional, Arnaldi, Dario, additional, Roccatagliata, Luca, additional, Chincarini, Andrea, additional, and Nobili, Flavio, additional

Published
2020
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16. MRI predictors of amyloid pathology: results from the EMIF-AD Multimodal Biomarker Discovery study

Author

ten Kate, Mara, Redolfi, Alberto, Peira, Enrico, Bos, Isabelle, Vos, Stephanie J., Vandenberghe, Rik, Gabel, Silvy, Schaeverbeke, Jolien, Scheltens, Philip, Blin, Olivier, Richardson, Jill C., Bordet, Regis, Wallin, Anders, Eckerstrom, Carl, Molinuevo, José Luis, Engelborghs, Sebastiaan, Van Broeckhoven, Christine, Martinez-Lage, Pablo, Popp, Julius, Tsolaki, Magdalini, Verhey, Frans R. J., Baird, Alison L., Legido-Quigley, Cristina, Bertram, Lars, Dobricic, Valerija, Zetterberg, Henrik, Lovestone, Simon, Streffer, Johannes, Bianchetti, Silvia, Novak, Gerald P., Revillard, Jerome, Gordon, Mark F., Xie, Zhiyong, Wottschel, Viktor, Frisoni, Giovanni, Visser, Pieter Jelle, and Barkhof, Frederik

Published
2018
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17. The Role of Monoaminergic Tones and Brain Metabolism in Cognition in De Novo Parkinson’s Disease

Author

Orso, Beatrice, primary, Arnaldi, Dario, additional, Peira, Enrico, additional, Famá, Francesco, additional, Giorgetti, Laura, additional, Girtler, Nicola, additional, Brugnolo, Andrea, additional, Mattioli, Pietro, additional, Biassoni, Erica, additional, Donniaquio, Andrea, additional, Massa, Federico, additional, Bauckneht, Matteo, additional, Miceli, Alberto, additional, Morbelli, Silvia, additional, Nobili, Flavio, additional, and Pardini, Matteo, additional

Published
2022
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18. Advances and perspectives in amyloid PET quantitative interpretation

Author

Peira, Enrico

Subjects
Settore MED/36 - Diagnostica per Immagini e Radioterapia, Settore MED/26 - Neurologia
Abstract

Amyloid imaging refers to a diagnostic examination that allows for the in-vivo detection of amyloid aggregation, considered a pathological hallmark of Alzheimer's disease (AD). The technique of choice for amyloid imaging is PET with appropriate radioligands, which has become a key tool in the diagnosis and research framework of AD. Due to the non-straightforward relationship between the presentation of the disease and the underlying molecular pathology, the diagnosis based purely on the clinical manifestation is a non-trivial task. Therefore, a great interest has developed around the methodologies for the assessment of in-vivo biomarkers (such as the amyloid aggregation) that can be used to complement the clinical evaluation and provide direct evidence of the core features of the pathology. There are several evolving aspects related to the analysis of amyloid PET in clinical setting. For example, it is becoming of common wisdom that the dichotomous classification - classically used in clinical practice - based solely on visual analysis is inadequate, as it does not provide information on the level of positivity and is used to describe a phenomenon that is gradual and can last up to 15 years. Quantitative approaches that provide numerical estimates of the physiological processes of interest may help by giving the opportunity of ranking brain amyloidosis to find out, for example, patients who would benefit from a treatment. These approaches are constantly evolving and there is currently no consensus on which is the best way to perform a quantitative analysis of amyloid PET images or which is the most feasible in clinical setting. Other relevant issues are related to the differences between radiotracers and to image quality factors that that can affect the interpretation of the scan even for expert readers even when supported by quantification. Another poorly understood aspect is the potential information that is lost in amyloid PET images using current analysis pipelines. Up to now, the amyloid imaging data have mainly been used for the definition of global amyloid profile. Recent studies have shown that this imaging modality can provide much more detailed information when assessed at regional level. In this context, my research focused mainly on two aspects of amyloid PET assessment. The first is related to technical issues that can arise in the evaluation of the scans, such as the application of an appropriate analysis method to different radiotracers, the comparison of multiple-reader visual evaluations and the effect of image quality. A novel quantitative approach has also been developed, validated and compared to both standard and highly sophisticated techniques. The second aspect is more clinical-related and has to do with the possible interpretation of regional amyloid burden and the assessment of the relationship between the regional load, the cognitive decline and the regional tau (the other major biomarker in Alzheimer?s disease).

Published
2022
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19. The Free and Cued Selective Reminding Test: Discriminative Values in a Naturalistic Cohort

Author

Girtler, Nicola, primary, Chincarini, Andrea, additional, Brugnolo, Andrea, additional, Doglione, Elisa, additional, Orso, Beatrice, additional, Morbelli, Silvia, additional, Massa, Federico, additional, Peira, Enrico, additional, Biassoni, Erica, additional, Donniaquio, Andrea, additional, Grisanti, Stefano, additional, Pardini, Matteo, additional, Arnaldi, Dario, additional, and Nobili, Flavio, additional

Published
2022
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20. The Role of Hub and Spoke Regions in Theory of Mind in Early Alzheimer’s Disease and Frontotemporal Dementia

Author

Orso, Beatrice, primary, Lorenzini, Luigi, additional, Arnaldi, Dario, additional, Girtler, Nicola, additional, Brugnolo, Andrea, additional, Doglione, Elisa, additional, Mattioli, Pietro, additional, Biassoni, Erica, additional, Massa, Federico, additional, Peira, Enrico, additional, Bauckneht, Matteo, additional, Donegani, Maria I., additional, Morbelli, Silvia, additional, Nobili, Flavio, additional, and Pardini, Matteo, additional

Published
2022
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21. Towards an Automated Approach to the Semi-Quantification of [ 18 F]F-DOPA PET in Pediatric-Type Diffuse Gliomas.

Author

Peira, Enrico, Sensi, Francesco, Rei, Luca, Gianeri, Ruben, Tortora, Domenico, Fiz, Francesco, Piccardo, Arnoldo, Bottoni, Gianluca, Morana, Giovanni, and Chincarini, Andrea

Subjects
*GLIOMAS, *POSITRON emission tomography, *MAGNETIC resonance imaging, *PEARSON correlation (Statistics), *CHILD patients
Abstract

Background: This study aims to evaluate the use of a computer-aided, semi-quantification approach to [18F]F-DOPA positron emission tomography (PET) in pediatric-type diffuse gliomas (PDGs) to calculate the tumor-to-background ratio. Methods: A total of 18 pediatric patients with PDGs underwent magnetic resonance imaging and [18F]F-DOPA PET, which were analyzed using both manual and automated procedures. The former provided a tumor-to-normal-tissue ratio (TN) and tumor-to-striatal-tissue ratio (TS), while the latter provided analogous scores (tn, ts). We tested the correlation, consistency, and ability to stratify grading and survival between these methods. Results: High Pearson correlation coefficients resulted between the ratios calculated with the two approaches: ρ = 0.93 (p < 10−4) and ρ = 0.814 (p < 10−4). The analysis of the residuals suggested that tn and ts were more consistent than TN and TS. Similarly to TN and TS, the automatically computed scores showed significant differences between low- and high-grade gliomas (p ≤ 10−4, t-test) and the overall survival was significantly shorter in patients with higher values when compared to those with lower ones (p < 10−3, log-rank test). Conclusions: This study suggested that the proposed computer-aided approach could yield similar results to the manual procedure in terms of diagnostic and prognostic information. [ABSTRACT FROM AUTHOR]

Published
2023
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24. Added value of semiquantitative analysis of brain FDG-PET for the differentiation between MCI-Lewy bodies and MCI due to Alzheimer’s disease

Author

Massa, Federico, primary, Chincarini, Andrea, additional, Bauckneht, Matteo, additional, Raffa, Stefano, additional, Peira, Enrico, additional, Arnaldi, Dario, additional, Pardini, Matteo, additional, Pagani, Marco, additional, Orso, Beatrice, additional, Donegani, Maria Isabella, additional, Brugnolo, Andrea, additional, Biassoni, Erica, additional, Mattioli, Pietro, additional, Girtler, Nicola, additional, Guerra, Ugo Paolo, additional, Morbelli, Silvia, additional, and Nobili, Flavio, additional

Published
2021
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25. Polysomnographic correlates of sleep disturbances in de novo, drug naïve Parkinson’s Disease

Author

Orso, Beatrice, primary, Famà, Francesco, additional, Giorgetti, Laura, additional, Mattioli, Pietro, additional, Donniaquio, Andrea, additional, Girtler, Nicola, additional, Brugnolo, Andrea, additional, Massa, Federico, additional, Peira, Enrico, additional, Pardini, Matteo, additional, Morbelli, Silvia, additional, Nobili, Flavio, additional, and Arnaldi, Dario, additional

Published
2021
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26. Associations among education, age, and the dementia with Lewy bodies (DLB) metabolic pattern: A European-DLB consortium project

Author

Bauckneht, Matteo, Chincarini, Andrea, Brendel, Matthias, Rominger, Axel, Beyer, Leonie, Bruffaerts, Rose, Vandenberghe, Rik, Kramberger, Milica G., Trost, Maja, Garibotto, Valentina, Nicastro, Nicolas, Frisoni, Giovanni B., Lemstra, Afina W., Berckel, Bart N. M., Pilotto, Andrea, Padovani, Alessandro, Ochoa-Figueroa, Miguel A., Davidsson, Anette, Camacho, Valle, Peira, Enrico, Arnaldi, Dario, Pardini, Matteo, Donegani, Maria Isabella, Raffa, Stefano, Miceli, Alberto, Sambuceti, Gianmario, Aarsland, Dag, Nobili, Flavio, Morbelli, Silvia, Bauckneht, Matteo, Chincarini, Andrea, Brendel, Matthias, Rominger, Axel, Beyer, Leonie, Bruffaerts, Rose, Vandenberghe, Rik, Kramberger, Milica G., Trost, Maja, Garibotto, Valentina, Nicastro, Nicolas, Frisoni, Giovanni B., Lemstra, Afina W., Berckel, Bart N. M., Pilotto, Andrea, Padovani, Alessandro, Ochoa-Figueroa, Miguel A., Davidsson, Anette, Camacho, Valle, Peira, Enrico, Arnaldi, Dario, Pardini, Matteo, Donegani, Maria Isabella, Raffa, Stefano, Miceli, Alberto, Sambuceti, Gianmario, Aarsland, Dag, Nobili, Flavio, and Morbelli, Silvia

Abstract

Introduction We assessed the influence of education as a proxy of cognitive reserve and age on the dementia with Lewy bodies (DLB) metabolic pattern. Methods Brain 18F-fluorodeoxyglucose positron emission tomography and clinical/demographic information were available in 169 probable DLB patients included in the European DLB-consortium database. Principal component analysis identified brain regions relevant to local data variance. A linear regression model was applied to generate age- and education-sensitive maps corrected for Mini-Mental State Examination score, sex (and either education or age). Results Age negatively covaried with metabolism in bilateral middle and superior frontal cortex, anterior and posterior cingulate, reducing the expression of the DLB-typical cingulate island sign (CIS). Education negatively covaried with metabolism in the left inferior parietal cortex and precuneus (making the CIS more prominent). Discussion These findings point out the importance of tailoring interpretation of DLB biomarkers considering the concomitant effect of individual, non-disease-related variables such as age and cognitive reserve.

Published
2021
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28. Associations among education, age, and the dementia with Lewy bodies (DLB) metabolic pattern: A European‐DLB consortium project

Author

Bauckneht, Matteo, primary, Chincarini, Andrea, additional, Brendel, Matthias, additional, Rominger, Axel, additional, Beyer, Leonie, additional, Bruffaerts, Rose, additional, Vandenberghe, Rik, additional, Kramberger, Milica G., additional, Trost, Maja, additional, Garibotto, Valentina, additional, Nicastro, Nicolas, additional, Frisoni, Giovanni B., additional, Lemstra, Afina W., additional, Berckel, Bart N. M., additional, Pilotto, Andrea, additional, Padovani, Alessandro, additional, Ochoa‐Figueroa, Miguel A., additional, Davidsson, Anette, additional, Camacho, Valle, additional, Peira, Enrico, additional, Arnaldi, Dario, additional, Pardini, Matteo, additional, Donegani, Maria Isabella, additional, Raffa, Stefano, additional, Miceli, Alberto, additional, Sambuceti, Gianmario, additional, Aarsland, Dag, additional, Nobili, Flavio, additional, and Morbelli, Silvia, additional

Published
2021
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29. Metabolic correlates of dopaminergic loss in dementia with lewy bodies

Author

Huber, Maria, Beyer, Leonie, Prix, Catharina, Schoenecker, Sonja, Palleis, Carla, Rauchmann, Boris-Stephan, Morbelli, Silvia, Chincarini, Andrea, Bruffaerts, Rose, Vandenberghe, Rik, Van Laere, Koen, Kramberger, Milica G., Trost, Maja, Grmek, Marko, Garibotto, Valentina, Nicastro, Nicolas, Frisoni, Giovanni B., Lemstra, Afina W., van der Zande, Jessica, Pilotto, Andrea, Padovani, Alessandro, Garcia-Ptacek, Sara, Savitcheva, Irina, Ochoa-Figueroa, Miguel A., Davidsson, Anette, Camacho, Valle, Peira, Enrico, Arnaldi, Dario, Bauckneht, Matteo, Pardini, Matteo, Sambuceti, Gianmario, Voeglein, Jonathan, Schnabel, Jonas, Unterrainer, Marcus, Perneczky, Robert, Pogarell, Oliver, Buerger, Katharina, Catak, Cihan, Bartenstein, Peter, Cumming, Paul, Ewers, Michael, Danek, Adrian, Levin, Johannes, Aarsland, Dag, Nobili, Flavio, Rominger, Axel, Brendel, Matthias, Huber, Maria, Beyer, Leonie, Prix, Catharina, Schoenecker, Sonja, Palleis, Carla, Rauchmann, Boris-Stephan, Morbelli, Silvia, Chincarini, Andrea, Bruffaerts, Rose, Vandenberghe, Rik, Van Laere, Koen, Kramberger, Milica G., Trost, Maja, Grmek, Marko, Garibotto, Valentina, Nicastro, Nicolas, Frisoni, Giovanni B., Lemstra, Afina W., van der Zande, Jessica, Pilotto, Andrea, Padovani, Alessandro, Garcia-Ptacek, Sara, Savitcheva, Irina, Ochoa-Figueroa, Miguel A., Davidsson, Anette, Camacho, Valle, Peira, Enrico, Arnaldi, Dario, Bauckneht, Matteo, Pardini, Matteo, Sambuceti, Gianmario, Voeglein, Jonathan, Schnabel, Jonas, Unterrainer, Marcus, Perneczky, Robert, Pogarell, Oliver, Buerger, Katharina, Catak, Cihan, Bartenstein, Peter, Cumming, Paul, Ewers, Michael, Danek, Adrian, Levin, Johannes, Aarsland, Dag, Nobili, Flavio, Rominger, Axel, and Brendel, Matthias

Abstract

Background Striatal dopamine deficiency and metabolic changes are well-known phenomena in dementia with Lewy bodies and can be quantified in vivo by I-123-Ioflupane brain single-photon emission computed tomography of dopamine transporter and F-18-fluorodesoxyglucose PET. However, the linkage between both biomarkers is ill-understood. Objective We used the hitherto largest study cohort of combined imaging from the European consortium to elucidate the role of both biomarkers in the pathophysiological course of dementia with Lewy bodies. Methods We compared striatal dopamine deficiency and glucose metabolism of 84 dementia with Lewy body patients and comparable healthy controls. After normalization of data, we tested their correlation by region-of-interest-based and voxel-based methods, controlled for study center, age, sex, education, and current cognitive impairment. Metabolic connectivity was analyzed by inter-region coefficients stratified by dopamine deficiency and compared to healthy controls. Results There was an inverse relationship between striatal dopamine availability and relative glucose hypermetabolism, pronounced in the basal ganglia and in limbic regions. With increasing dopamine deficiency, metabolic connectivity showed strong deteriorations in distinct brain regions implicated in disease symptoms, with greatest disruptions in the basal ganglia and limbic system, coincident with the pattern of relative hypermetabolism. Conclusions Relative glucose hypermetabolism and disturbed metabolic connectivity of limbic and basal ganglia circuits are metabolic correlates of dopamine deficiency in dementia with Lewy bodies. Identification of specific metabolic network alterations in patients with early dopamine deficiency may serve as an additional supporting biomarker for timely diagnosis of dementia with Lewy bodies. (c) 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society., Funding Agencies|Velox Foundation [project 1123]; Schweizerischer Nationalfonds zur Forderung der Wissenschaftlichen Forschung [SNF 320030_169876]

Published
2020
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30. MRI PREDICTORS OF AMYLOID PATHOLOGY: RESULTS FROM THE EMIF-AD BIOMARKER DISCOVERY STUDY

Author

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

Published
2018
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31. Metabolic Patterns across core features in Dementia with Lewy Bodies (DLB)

Author

Morbelli, Silvia, Chincarini, Andrea, Brendel, Matthias, Rominger, Axel Oliver, Bruffaerts, Rose, Vandenberghe, Rik, Kramberger, Milica G., Trost, Maja, Garibotto, Valentina, Nicastro, Nicolas, Frisoni, Giovanni B., Lemstra, Afina W., Van Der Zande, Jessica, Pilotto, Andrea, Padovani, Alessandro, Garcia-Ptacek, Sara, Savitcheva, Irina, Ochoa-Figueroa, Miguel A, Davidsson, Annette, Camacho, Valle, Peira, Enrico, Arnaldi, Dario, Bauckneht, Matteo, Pardini, Matteo, Sambuceti, Gianmario, Aarsland, Dag, and Nobili, Flavio

Subjects
nervous system, mental disorders, 610 Medicine & health, behavioral disciplines and activities
Abstract

OBJECTIVE: To identify brain regions whose metabolic impairment contributes to DLB clinical core features expression and to assess the influence of severity of global cognitive impairment on the DLB-hypometabolic-pattern. METHODS: Brain FDG-PET and information on core features were available in 171 patients belonging to the imaging repository of the European DLB-consortium. Principal component analysis was applied to identify brain regions relevant to the local data variance. A linear regression model was applied to generate core feature-specific patterns controlling for the main confounding variables (MMSE, Age, Education, Gender, and Center). Regression analysis to the locally-normalized intensities was performed to generate a MMSE score-sensitive map. RESULTS: Parkinsonism negatively covaried with bilateral parietal, precuneus and anterior cingulate metabolism, visual-hallucinations with bilateral dorsolateral-frontal cortex, posterior cingulate and parietal metabolism and RBD with bilateral parieto-occipital cortex, precuneus and ventrolateral-frontal metabolism. VH and RBD shared a positive covariance with metabolism in medial temporal lobe, cerebellum, brainstem, basal ganglia, thalami, orbitofrontal and sensorimotor cortex. Cognitive fluctuations negatively covaried with occipital metabolism and positively with parietal lobes metabolism. MMSE positively covaried with metabolism in left superior frontal gyrus, bilateral-parietal cortex, and left precuneus, and negatively with metabolism in insula, medial frontal gyrus, hippocampus in the left hemisphere and in right cerebellum. INTERPRETATION: Regions of more preserved metabolism are relatively consistent across the variegate DLB spectrum. By contrast, core features were associated to more prominent hypometabolism in specific regions thus suggesting a close clinical-imaging correlation, reflecting the interplay between topography of neurodegeneration and clinical presentation in DLB patients. This article is protected by copyright. All rights reserved.

Published
2019
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32. Metabolic Correlates of Dopaminergic Loss in Dementia with Lewy Bodies

Author

Huber, Maria, primary, Beyer, Leonie, additional, Prix, Catharina, additional, Schönecker, Sonja, additional, Palleis, Carla, additional, Rauchmann, Boris‐Stephan, additional, Morbelli, Silvia, additional, Chincarini, Andrea, additional, Bruffaerts, Rose, additional, Vandenberghe, Rik, additional, Van Laere, Koen, additional, Kramberger, Milica G., additional, Trost, Maja, additional, Grmek, Marko, additional, Garibotto, Valentina, additional, Nicastro, Nicolas, additional, Frisoni, Giovanni B., additional, Lemstra, Afina W., additional, Zande, Jessica, additional, Pilotto, Andrea, additional, Padovani, Alessandro, additional, Garcia‐Ptacek, Sara, additional, Savitcheva, Irina, additional, Ochoa‐Figueroa, Miguel A., additional, Davidsson, Anette, additional, Camacho, Valle, additional, Peira, Enrico, additional, Arnaldi, Dario, additional, Bauckneht, Matteo, additional, Pardini, Matteo, additional, Sambuceti, Gianmario, additional, Vöglein, Jonathan, additional, Schnabel, Jonas, additional, Unterrainer, Marcus, additional, Perneczky, Robert, additional, Pogarell, Oliver, additional, Buerger, Katharina, additional, Catak, Cihan, additional, Bartenstein, Peter, additional, Cumming, Paul, additional, Ewers, Michael, additional, Danek, Adrian, additional, Levin, Johannes, additional, Aarsland, Dag, additional, Nobili, Flavio, additional, Rominger, Axel, additional, and Brendel, Matthias, additional

Published
2019
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33. Metabolic patterns across core features in dementia with lewy bodies

Author

Morbelli, Silvia, primary, Chincarini, Andrea, additional, Brendel, Matthias, additional, Rominger, Axel, additional, Bruffaerts, Rose, additional, Vandenberghe, Rik, additional, Kramberger, Milica G., additional, Trost, Maja, additional, Garibotto, Valentina, additional, Nicastro, Nicolas, additional, Frisoni, Giovanni B., additional, Lemstra, Afina W., additional, Zande, Jessica, additional, Pilotto, Andrea, additional, Padovani, Alessandro, additional, Garcia‐Ptacek, Sara, additional, Savitcheva, Irina, additional, Ochoa‐Figueroa, Miguel A., additional, Davidsson, Annette, additional, Camacho, Valle, additional, Peira, Enrico, additional, Arnaldi, Dario, additional, Bauckneht, Matteo, additional, Pardini, Matteo, additional, Sambuceti, Gianmario, additional, Aarsland, Dag, additional, and Nobili, Flavio, additional

Published
2019
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34. Metabolic patterns across core features in dementia with lewy bodies

Author

Morbelli, Silvia, Chincarini, Andrea, Brendel, Matthias, Rominger, Axel, Bruffaerts, Rose, Vandenberghe, Rik, Kramberger, Milica G., Trost, Maja, Garibotto, Valentina, Nicastro, Nicolas, Frisoni, Giovanni B., Lemstra, Afina W., van der Zande, Jessica, Pilotto, Andrea, Padovani, Alessandro, Garcia-Ptacek, Sara, Savitcheva, Irina, Ochoa-Figueroa, Miguel A., Davidsson, Anette, Camacho, Valle, Peira, Enrico, Arnaldi, Dario, Bauckneht, Matteo, Pardini, Matteo, Sambuceti, Gianmario, Aarsland, Dag, Nobili, Flavio, Morbelli, Silvia, Chincarini, Andrea, Brendel, Matthias, Rominger, Axel, Bruffaerts, Rose, Vandenberghe, Rik, Kramberger, Milica G., Trost, Maja, Garibotto, Valentina, Nicastro, Nicolas, Frisoni, Giovanni B., Lemstra, Afina W., van der Zande, Jessica, Pilotto, Andrea, Padovani, Alessandro, Garcia-Ptacek, Sara, Savitcheva, Irina, Ochoa-Figueroa, Miguel A., Davidsson, Anette, Camacho, Valle, Peira, Enrico, Arnaldi, Dario, Bauckneht, Matteo, Pardini, Matteo, Sambuceti, Gianmario, Aarsland, Dag, and Nobili, Flavio

Abstract

Objective To identify brain regions whose metabolic impairment contributes to dementia with Lewy bodies (DLB) clinical core features expression and to assess the influence of severity of global cognitive impairment on the DLB hypometabolic pattern. Methods Brain fluorodeoxyglucose positron emission tomography and information on core features were available in 171 patients belonging to the imaging repository of the European DLB Consortium. Principal component analysis was applied to identify brain regions relevant to the local data variance. A linear regression model was applied to generate core‐feature–specific patterns controlling for the main confounding variables (Mini‐Mental State Examination [MMSE], age, education, gender, and center). Regression analysis to the locally normalized intensities was performed to generate an MMSE‐sensitive map. Results Parkinsonism negatively covaried with bilateral parietal, precuneus, and anterior cingulate metabolism; visual hallucinations (VH) with bilateral dorsolateral–frontal cortex, posterior cingulate, and parietal metabolism; and rapid eye movement sleep behavior disorder (RBD) with bilateral parieto‐occipital cortex, precuneus, and ventrolateral–frontal metabolism. VH and RBD shared a positive covariance with metabolism in the medial temporal lobe, cerebellum, brainstem, basal ganglia, thalami, and orbitofrontal and sensorimotor cortex. Cognitive fluctuations negatively covaried with occipital metabolism and positively with parietal lobe metabolism. MMSE positively covaried with metabolism in the left superior frontal gyrus, bilateral–parietal cortex, and left precuneus, and negatively with metabolism in the insula, medial frontal gyrus, hippocampus in the left hemisphere, and right cerebellum. Interpretation Regions of more preserved metabolism are relatively consistent across the variegate DLB spectrum. By contrast, core features were associated with more prominent hypometabolism in specific regions, thus suggesting a

Published
2019
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35. F1‐02‐03: MRI PREDICTORS OF AMYLOID PATHOLOGY: RESULTS FROM THE EMIF‐AD BIOMARKER DISCOVERY STUDY

Author

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

Published
2018
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36. P2‐458: PREDICTING COGNITIVE DECLINE THROUGH STRUCTURAL MRI BIOMARKERS: RESULTS FROM THE EMIF‐AD BIOMARKER DISCOVERY STUDY

Author

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

Published
2018
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37. Anatomical and neurochemical bases of theory of mind in de novoParkinson's Disease

Author

Orso, Beatrice, Arnaldi, Dario, Famà, Francesco, Girtler, Nicola, Brugnolo, Andrea, Doglione, Elisa, Filippi, Laura, Massa, Federico, Peira, Enrico, Bauckneht, Matteo, Morbelli, Silvia, Nobili, Flavio, and Pardini, Matteo

Abstract

Theory of mind (ToM) deficit is a frequent finding in subjects with neurological and psychiatric conditions. While a number of brain regions play a role in ToM, to date the contribution of the diffuse projection systems is less understood.

Published
2020
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38. Accuracy and generalization capability of an automatic method for the detection of typical brain hypometabolism in prodromal Alzheimer disease.

Author

for the Alzheimer's Disease Neuroimaging Initiative, De Carli, Fabrizio, Nobili, Flavio, Massa, Federico, Grazzini, Matteo, Arnaldi, Dario, Pagani, Marco, Jonsson, Cathrine, Bauckneht, Matteo, Morbelli, Silvia, and Peira, Enrico

Subjects
METABOLIC disorder diagnosis, BRAIN metabolism, GENETICS of Alzheimer's disease, POSITRON emission, FLUORODEOXYGLUCOSE F18, SUPPORT vector machines
Abstract

Purpose: The aim of this study was to verify the reliability and generalizability of an automatic tool for the detection of Alzheimer-related hypometabolic pattern based on a Support-Vector-Machine (SVM) model analyzing 18F-fluorodeoxyglucose (FDG) PET data.Methods: The SVM model processed metabolic data from anatomical volumes of interest also considering interhemispheric asymmetries. It was trained on a homogeneous dataset from a memory clinic center and tested on an independent multicentric dataset drawn from the Alzheimer's Disease Neuroimaging Initiative. Subjects were included in the study and classified based on a diagnosis confirmed after an adequate follow-up time.Results: The accuracy of the discrimination between patients with Alzheimer Disease (AD), in either prodromal or dementia stage, and normal aging subjects was 95.8%, after cross-validation, in the training set. The accuracy of the same model in the testing set was 86.5%. The role of the two datasets was then reversed, and the accuracy was 89.8% in the multicentric training set and 88.0% in the monocentric testing set. The classification rate was also evaluated in different subgroups, including non-converter mild cognitive impairment (MCI) patients, subjects with MCI reverted to normal conditions and subjects with non-confirmed memory concern. The percent of pattern detections increased from 77% in early prodromal AD to 91% in AD dementia, while it was about 10% for healthy controls and non-AD patients.Conclusions: The present findings show a good level of reproducibility and generalizability of a model for detecting the hypometabolic pattern in AD and confirm the accuracy of FDG-PET in Alzheimer disease. [ABSTRACT FROM AUTHOR]

Published
2019
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39. PREDICTING COGNITIVE DECLINE THROUGH STRUCTURAL MRI BIOMARKERS: RESULTS FROM THE EMIF-AD BIOMARKER DISCOVERY STUDY

Author

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

Published
2018
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41. Additional file 1: of MRI predictors of amyloid pathology: results from the EMIF-AD Multimodal Biomarker Discovery study

Author

Kate, Mara Ten, Redolfi, Alberto, Peira, Enrico, Bos, Isabelle, Vos, Stephanie, Vandenberghe, Rik, Gabel, Silvy, Schaeverbeke, Jolien, Scheltens, Philip, Blin, Olivier, Richardson, Jill, Bordet, Regis, Wallin, Anders, Eckerstrom, Carl, JosĂŠ Molinuevo, Engelborghs, Sebastiaan, Broeckhoven, Christine Van, Martinez-Lage, Pablo, Popp, Julius, Tsolaki, Magdalini, Verhey, Frans, Baird, Alison, Legido-Quigley, Cristina, Bertram, Lars, Dobricic, Valerija, Zetterberg, Henrik, Lovestone, Simon, Streffer, Johannes, Bianchetti, Silvia, Novak, Gerald, Revillard, Jerome, Gordon, Mark, Zhiyong Xie, Wottschel, Viktor, Frisoni, Giovanni, Visser, Pieter, and Barkhof, Frederik

Subjects
3. Good health
Abstract

Additional Tables S1â S8 (PDF 264 kb)

42. Additional file 2: of MRI predictors of amyloid pathology: results from the EMIF-AD Multimodal Biomarker Discovery study

Author

Kate, Mara Ten, Redolfi, Alberto, Peira, Enrico, Bos, Isabelle, Vos, Stephanie, Vandenberghe, Rik, Gabel, Silvy, Schaeverbeke, Jolien, Scheltens, Philip, Blin, Olivier, Richardson, Jill, Bordet, Regis, Wallin, Anders, Eckerstrom, Carl, JosĂŠ Molinuevo, Engelborghs, Sebastiaan, Broeckhoven, Christine Van, Martinez-Lage, Pablo, Popp, Julius, Tsolaki, Magdalini, Verhey, Frans, Baird, Alison, Legido-Quigley, Cristina, Bertram, Lars, Dobricic, Valerija, Zetterberg, Henrik, Lovestone, Simon, Streffer, Johannes, Bianchetti, Silvia, Novak, Gerald, Revillard, Jerome, Gordon, Mark, Zhiyong Xie, Wottschel, Viktor, Frisoni, Giovanni, Visser, Pieter, and Barkhof, Frederik

Subjects
3. Good health
Abstract

Additional Figures S1â S3 (PDF 770 kb)

43. Additional file 1: of MRI predictors of amyloid pathology: results from the EMIF-AD Multimodal Biomarker Discovery study

Author

Kate, Mara Ten, Redolfi, Alberto, Peira, Enrico, Bos, Isabelle, Vos, Stephanie, Vandenberghe, Rik, Gabel, Silvy, Schaeverbeke, Jolien, Scheltens, Philip, Blin, Olivier, Richardson, Jill, Bordet, Regis, Wallin, Anders, Eckerstrom, Carl, JosĂŠ Molinuevo, Engelborghs, Sebastiaan, Broeckhoven, Christine Van, Martinez-Lage, Pablo, Popp, Julius, Tsolaki, Magdalini, Verhey, Frans, Baird, Alison, Legido-Quigley, Cristina, Bertram, Lars, Dobricic, Valerija, Zetterberg, Henrik, Lovestone, Simon, Streffer, Johannes, Bianchetti, Silvia, Novak, Gerald, Revillard, Jerome, Gordon, Mark, Zhiyong Xie, Wottschel, Viktor, Frisoni, Giovanni, Visser, Pieter, and Barkhof, Frederik

Subjects
3. Good health
Abstract

Additional Tables S1â S8 (PDF 264 kb)

44. Metabolic correlates of dopaminergic loss in dementia with lewy bodies

Author

Huber, Maria, Beyer, Leonie, Prix, Catharina, Schönecker, Sonja, Palleis, Carla, Rauchmann, Boris-Stephan, Morbelli, Silvia, Chincarini, Andrea, Bruffaerts, Rose, Vandenberghe, Rik, Van Laere, Koen, Kramberger, Milica G, Trost, Maja, Grmek, Marko, Garibotto, Valentina, Nicastro, Nicolas, Frisoni, Giovanni B, Lemstra, Afina W, Van Der Zande, Jessica, Pilotto, Andrea, Padovani, Alessandro, Garcia-Ptacek, Sara, Savitcheva, Irina, Ochoa-Figueroa, Miguel A, Davidsson, Anette, Camacho, Valle, Peira, Enrico, Arnaldi, Dario, Bauckneht, Matteo, Pardini, Matteo, Sambuceti, Gianmario, Vöglein, Jonathan, Schnabel, Jonas, Unterrainer, Marcus, Perneczky, Robert, Pogarell, Oliver, Buerger, Katharina, Catak, Cihan, Bartenstein, Peter, Cumming, Paul, Ewers, Michael, Danek, Adrian, Levin, Johannes, Aarsland, Dag, Nobili, Flavio, Rominger, Axel, and Brendel, Matthias

Subjects
610 Medicine & health, 3. Good health
Abstract

BACKGROUND Striatal dopamine deficiency and metabolic changes are well-known phenomena in dementia with Lewy bodies and can be quantified in vivo by 123 I-Ioflupane brain single-photon emission computed tomography of dopamine transporter and 18 F-fluorodesoxyglucose PET. However, the linkage between both biomarkers is ill-understood. OBJECTIVE We used the hitherto largest study cohort of combined imaging from the European consortium to elucidate the role of both biomarkers in the pathophysiological course of dementia with Lewy bodies. METHODS We compared striatal dopamine deficiency and glucose metabolism of 84 dementia with Lewy body patients and comparable healthy controls. After normalization of data, we tested their correlation by region-of-interest-based and voxel-based methods, controlled for study center, age, sex, education, and current cognitive impairment. Metabolic connectivity was analyzed by inter-region coefficients stratified by dopamine deficiency and compared to healthy controls. RESULTS There was an inverse relationship between striatal dopamine availability and relative glucose hypermetabolism, pronounced in the basal ganglia and in limbic regions. With increasing dopamine deficiency, metabolic connectivity showed strong deteriorations in distinct brain regions implicated in disease symptoms, with greatest disruptions in the basal ganglia and limbic system, coincident with the pattern of relative hypermetabolism. CONCLUSIONS Relative glucose hypermetabolism and disturbed metabolic connectivity of limbic and basal ganglia circuits are metabolic correlates of dopamine deficiency in dementia with Lewy bodies. Identification of specific metabolic network alterations in patients with early dopamine deficiency may serve as an additional supporting biomarker for timely diagnosis of dementia with Lewy bodies. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

45. Metabolic Correlates of Dopaminergic Loss in Dementia with Lewy Bodies.

Author

Huber M, Beyer L, Prix C, Schönecker S, Palleis C, Rauchmann BS, Morbelli S, Chincarini A, Bruffaerts R, Vandenberghe R, Van Laere K, Kramberger MG, Trost M, Grmek M, Garibotto V, Nicastro N, Frisoni GB, Lemstra AW, van der Zande J, Pilotto A, Padovani A, Garcia-Ptacek S, Savitcheva I, Ochoa-Figueroa MA, Davidsson A, Camacho V, Peira E, Arnaldi D, Bauckneht M, Pardini M, Sambuceti G, Vöglein J, Schnabel J, Unterrainer M, Perneczky R, Pogarell O, Buerger K, Catak C, Bartenstein P, Cumming P, Ewers M, Danek A, Levin J, Aarsland D, Nobili F, Rominger A, and Brendel M

Subjects
Brain, Cohort Studies, Dopamine, Humans, Lewy Bodies, Lewy Body Disease diagnostic imaging
Abstract

Background: Striatal dopamine deficiency and metabolic changes are well-known phenomena in dementia with Lewy bodies and can be quantified in vivo by 123 I-Ioflupane brain single-photon emission computed tomography of dopamine transporter and 18 F-fluorodesoxyglucose PET. However, the linkage between both biomarkers is ill-understood., Objective: We used the hitherto largest study cohort of combined imaging from the European consortium to elucidate the role of both biomarkers in the pathophysiological course of dementia with Lewy bodies., Methods: We compared striatal dopamine deficiency and glucose metabolism of 84 dementia with Lewy body patients and comparable healthy controls. After normalization of data, we tested their correlation by region-of-interest-based and voxel-based methods, controlled for study center, age, sex, education, and current cognitive impairment. Metabolic connectivity was analyzed by inter-region coefficients stratified by dopamine deficiency and compared to healthy controls., Results: There was an inverse relationship between striatal dopamine availability and relative glucose hypermetabolism, pronounced in the basal ganglia and in limbic regions. With increasing dopamine deficiency, metabolic connectivity showed strong deteriorations in distinct brain regions implicated in disease symptoms, with greatest disruptions in the basal ganglia and limbic system, coincident with the pattern of relative hypermetabolism., Conclusions: Relative glucose hypermetabolism and disturbed metabolic connectivity of limbic and basal ganglia circuits are metabolic correlates of dopamine deficiency in dementia with Lewy bodies. Identification of specific metabolic network alterations in patients with early dopamine deficiency may serve as an additional supporting biomarker for timely diagnosis of dementia with Lewy bodies. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society., (© 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.)

Published
2020
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