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1. Amyloid pathology and vascular risk are associated with distinct patterns of cerebral white matter hyperintensities: A multicenter study in 3132 memory clinic patients

Author

Biesbroek, J Matthijs, Coenen, Mirthe, DeCarli, Charles, Fletcher, Evan M, Maillard, Pauline M, Initiative, Alzheimer's Disease Neuroimaging, Barkhof, Frederik, Barnes, Josephine, Benke, Thomas, Chen, Christopher PLH, Dal‐Bianco, Peter, Dewenter, Anna, Duering, Marco, Enzinger, Christian, Ewers, Michael, Exalto, Lieza G, Franzmeier, Nicolai, Hilal, Saima, Hofer, Edith, Koek, Huiberdina L, Maier, Andrea B, McCreary, Cheryl R, Papma, Janne M, Paterson, Ross W, Pijnenburg, Yolande AL, Rubinski, Anna, Schmidt, Reinhold, Schott, Jonathan M, Slattery, Catherine F, Smith, Eric E, Sudre, Carole H, Steketee, Rebecca ME, Teunissen, Charlotte E, van den Berg, Esther, van der Flier, Wiesje M, Venketasubramanian, Narayanaswamy, Venkatraghavan, Vikram, Vernooij, Meike W, Wolters, Frank J, Xin, Xu, Kuijf, Hugo J, and Biessels, Geert Jan

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Alzheimer's Disease, Prevention, Dementia, Clinical Research, Acquired Cognitive Impairment, Aging, Neurodegenerative, Brain Disorders, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurological, Humans, Female, Middle Aged, Aged, Aged, 80 and over, Male, White Matter, Arteriolosclerosis, Amyloid beta-Peptides, Magnetic Resonance Imaging, amyloid pathology, arteriolosclerosis, dementia, lesion pattern, white matter hyperintensities, Alzheimer's Disease Neuroimaging Initiative, Geriatrics, Clinical sciences, Biological psychology
Abstract

IntroductionWhite matter hyperintensities (WMH) are associated with key dementia etiologies, in particular arteriolosclerosis and amyloid pathology. We aimed to identify WMH locations associated with vascular risk or cerebral amyloid-β1-42 (Aβ42)-positive status.MethodsIndividual patient data (n = 3,132; mean age 71.5 ± 9 years; 49.3% female) from 11 memory clinic cohorts were harmonized. WMH volumes in 28 regions were related to a vascular risk compound score (VRCS) and Aß42 status (based on cerebrospinal fluid or amyloid positron emission tomography), correcting for age, sex, study site, and total WMH volume.ResultsVRCS was associated with WMH in anterior/superior corona radiata (B = 0.034/0.038, p

Published
2024

3. Spatial distributions of white matter hyperintensities on brain MRI: A pooled analysis of individual participant data from 11 memory clinic cohorts

Author

Coenen, Mirthe, Biessels, Geert Jan, DeCarli, Charles, Fletcher, Evan F, Maillard, Pauline M, Initiative, Alzheimer's Disease Neuroimaging, Barkhof, Frederik, Barnes, Josephine, Benke, Thomas, Boomsma, Jooske MF, Chen, Christopher PLH, Dal-Bianco, Peter, Dewenter, Anna, Duering, Marco, Enzinger, Christian, Ewers, Michael, Exalto, Lieza G, Franzmeier, Nicolai, Groeneveld, Onno, Hilal, Saima, Hofer, Edith, Koek, Huiberdina L, Maier, Andrea B, McCreary, Cheryl R, Papma, Janne M, Paterson, Ross W, Pijnenburg, Yolande AL, Rubinski, Anna, Schmidt, Reinhold, Schott, Jonathan M, Slattery, Catherine F, Smith, Eric E, Sudre, Carole H, Steketee, Rebecca ME, van den Berg, Esther, van der Flier, Wiesje M, Venketasubramanian, Narayanaswamy, Vernooij, Meike W, Wolters, Frank J, Xin, Xu, Biesbroek, J Matthijs, and Kuijf, Hugo J

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Cerebrovascular, Networking and Information Technology R&D (NITRD), Neurosciences, Neurodegenerative, Alzheimer's Disease Related Dementias (ADRD), Machine Learning and Artificial Intelligence, Vascular Cognitive Impairment/Dementia, Aging, Acquired Cognitive Impairment, Dementia, Brain Disorders, Neurological, Humans, White Matter, Brain, Magnetic Resonance Imaging, Neuroimaging, Cognitive Dysfunction, Multicenter Studies as Topic, White matter hyperintensities, Brain MRI, Distribution frequencies, Lesion location, Alzheimer's Disease Neuroimaging Initiative, Biological psychology, Clinical and health psychology
Abstract

IntroductionThe spatial distribution of white matter hyperintensities (WMH) on MRI is often considered in the diagnostic evaluation of patients with cognitive problems. In some patients, clinicians may classify WMH patterns as "unusual", but this is largely based on expert opinion, because detailed quantitative information about WMH distribution frequencies in a memory clinic setting is lacking. Here we report voxel wise 3D WMH distribution frequencies in a large multicenter dataset and also aimed to identify individuals with unusual WMH patterns.MethodsIndividual participant data (N = 3525, including 777 participants with subjective cognitive decline, 1389 participants with mild cognitive impairment and 1359 patients with dementia) from eleven memory clinic cohorts, recruited through the Meta VCI Map Consortium, were used. WMH segmentations were provided by participating centers or performed in Utrecht and registered to the Montreal Neurological Institute (MNI)-152 brain template for spatial normalization. To determine WMH distribution frequencies, we calculated WMH probability maps at voxel level. To identify individuals with unusual WMH patterns, region-of-interest (ROI) based WMH probability maps, rule-based scores, and a machine learning method (Local Outlier Factor (LOF)), were implemented.ResultsWMH occurred in 82% of voxels from the white matter template with large variation between subjects. Only a small proportion of the white matter (1.7%), mainly in the periventricular areas, was affected by WMH in at least 20% of participants. A large portion of the total white matter was affected infrequently. Nevertheless, 93.8% of individual participants had lesions in voxels that were affected in less than 2% of the population, mainly located in subcortical areas. Only the machine learning method effectively identified individuals with unusual patterns, in particular subjects with asymmetric WMH distribution or with WMH at relatively rarely affected locations despite common locations not being affected.DiscussionAggregating data from several memory clinic cohorts, we provide a detailed 3D map of WMH lesion distribution frequencies, that informs on common as well as rare localizations. The use of data-driven analysis with LOF can be used to identify unusual patterns, which might serve as an alert that rare causes of WMH should be considered.

Published
2023

4. Heart rate variability and stroke or systemic embolism in patients with atrial fibrillation

Author

Aeschbacher, Stefanie, Bhend, Katalin, Blum, Steffen, Bonati, Leo H., Carmine, Désirée, Conen, David, Eken, Ceylan, Fischer, Urs, Girroy, Corinne, Hennings, Elisa, Krisai, Philipp, Kühne, Michael, Mäder, Nina, Meyer-Zürn, Christine, Meyre, Pascal B., Monsch, Andreas U., Mosher, Luke, Müller, Christian, Osswald, Stefan, Paladini, Rebecca E., Peter, Raffaele, Schweigler, Adrian, Sticherling, Christian, Szucs, Thomas, Völlmin, Gian, Aujesky, Drahomir, Fuhrer, Juerg, Roten, Laurent, Jung, Simon, Mattle, Heinrich, Netzer, Seraina, Adam, Luise, Aubert, Carole Elodie, Feller, Martin, Loewe, Axel, Moutzouri, Elisavet, Schneider, Claudio, Flückiger, Tanja, Groen, Cindy, Ehrsam, Lukas, Hellrigl, Sven, Nuoffer, Alexandra, Rakovic, Damiana, Schwab, Nathalie, Wenger, Rylana, Zarrabi Saffari, Tu Hanh, Rodondi, Nicolas, Reichlin, Tobias, Beynon, Christopher, Dillier, Roger, Deubelbeiss, Michèle, Eberli, Franz, Franzini, Christine, Juchli, Isabel, Liedtke, Claudia, Murugiah, Samira, Nadler, Jacqueline, Obst, Thayze, Roth, Jasmin, Schlomowitsch, Fiona, Schneider, Xiaoye, Studerus, Katrin, Tynan, Noreen, Weishaupt, Dominik, Müller, Andreas, Friedli, Corinne, Kuest, Silke, Scheuch, Karin, Hischier, Denise, Bonetti, Nicole, Grau, Alexandra, Villinger, Jonas, Laube, Eva, Baumgartner, Philipp, Filipovic, Mark, Frick, Marcel, Montrasio, Giulia, Leuenberger, Stefanie, Rutz, Franziska, Beer, Jürg-Hans, Auricchio, Angelo, Anesini, Adriana, Camporini, Cristina, Caputo, Maria Luce, Peronaci, Rebecca, Regoli, Francois, Ronchi, Martina, Conte, Giulio, Brenner, Roman, Altmann, David, Fink, Karin, Gemperle, Michaela, Ammann, Peter, Firmann, Mathieu, Foucras, Sandrine, Rime, Martine, Hayoz, Daniel, Berte, Benjamin, Bühler, Kathrin, Justi, Virgina, Kellner-Weldon, Frauke, Koch, Melanie, Mehmann, Brigitta, Meier, Sonja, Roth, Myriam, Ruckli-Kaeppeli, Andrea, Russi, Ian, Schmidt, Kai, Young, Mabelle, Kobza, Richard, Rigamonti, Elia, Cereda, Carlo, Cianfoni, Alessandro, De Perna, Maria Luisa, Frangi-Kultalahti, Jane, Mayer Melchiorre, Patrizia Assunta, Pin, Anica, Terrot, Tatiana, Vicari, Luisa, Moschovitis, Giorgio, Ehret, Georg, Gallet, Hervé, Guillermet, Elise, Lazeyras, Francois, Lovblad, Karl-Olof, Perret, Patrick, Tavel, Philippe, Teres, Cheryl, Shah, Dipen, Lauriers, Nathalie, Méan, Marie, Salzmann, Sandrine, Schläpfer, Jürg, Porretta, Alessandra Pia, Grêt, Andrea, Novak, Jan, Vitelli, Sandra, Stephan, Frank-Peter, Gallino, Augusto, Di Valentino, Marcello, Aebersold, Helena, Foster, Fabienne, Schwenkglenks, Matthias, Düring, Marco, Sinnecker, Tim, Altermatt, Anna, Amann, Michael, Huber, Petra, Hürbin, Manuel, Ruberte, Esther, Thöni, Alain, Würfel, Jens, Zuber, Vanessa, Coslovsky (Head), Michael, Neuschwander, Pia, Simon, Patrick, Wunderlin, Olivia, Schmid, Ramun, Baumann, Christian, Hämmerle, Peter, Schlageter, Vincent, Coslovsky, Michael, Coduri, Federica, Blum, Manuel R., Stauber, Annina, Beer, Jürg, and Zuern, Christine S.

Published
2024
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7. Imaging Markers of Vascular Brain Health: Quantification, Clinical Implications, and Future Directions

Author

Vemuri, Prashanthi, Decarli, Charles, and Duering, Marco

Subjects
Health Services and Systems, Health Sciences, Neurodegenerative, Biomedical Imaging, Behavioral and Social Science, Cardiovascular, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, Neurosciences, Aging, Alzheimer's Disease Related Dementias (ADRD), Vascular Cognitive Impairment/Dementia, Acquired Cognitive Impairment, Brain Disorders, Heart Disease, Alzheimer's Disease, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Neurological, Stroke, Good Health and Well Being, Alzheimer Disease, Biomarkers, Brain, Cerebrovascular Disorders, Cognitive Dysfunction, Health Status, Humans, Magnetic Resonance Imaging, Neuroimaging, Alzheimer disease, brain, biomarkers, cerebrovascular disease, cognition, dementia, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Neurology & Neurosurgery, Clinical sciences, Allied health and rehabilitation science
Abstract

Cerebrovascular disease (CVD) manifests through a broad spectrum of mechanisms that negatively impact brain and cognitive health. Oftentimes, CVD changes (excluding acute stroke) are insufficiently considered in aging and dementia studies which can lead to an incomplete picture of the etiologies contributing to the burden of cognitive impairment. Our goal with this focused review is 3-fold. First, we provide a research update on the current magnetic resonance imaging methods that can measure CVD lesions as well as early CVD-related brain injury specifically related to small vessel disease. Second, we discuss the clinical implications and relevance of these CVD imaging markers for cognitive decline, incident dementia, and disease progression in Alzheimer disease, and Alzheimer-related dementias. Finally, we present our perspective on the outlook and challenges that remain in the field. With the increased research interest in this area, we believe that reliable CVD imaging biomarkers for aging and dementia studies are on the horizon.

Published
2022

8. Instrumental validation of free water, peak‐width of skeletonized mean diffusivity, and white matter hyperintensities: MarkVCID neuroimaging kits

Author

Maillard, Pauline, Lu, Hanzhang, Arfanakis, Konstantinos, Gold, Brian T, Bauer, Christopher E, Zachariou, Valentinos, Stables, Lara, Wang, Danny JJ, Jann, Kay, Seshadri, Sudha, Duering, Marco, Hillmer, Laura J, Rosenberg, Gary A, Snoussi, Haykel, Sepehrband, Farshid, Habes, Mohamad, Singh, Baljeet, Kramer, Joel H, Corriveau, Roderick A, Singh, Herpreet, Schwab, Kristin, Helmer, Karl G, Greenberg, Steven M, Caprihan, Arvind, DeCarli, Charles, Satizabal, Claudia L, and Consortium, for the MarkVCID

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Prevention, Biomedical Imaging, Clinical Trials and Supportive Activities, Neurosciences, Clinical Research, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, biomarker, diffusion tensor imaging, free water, magnetic resonance imaging, peak-width skeletonized mean diffusivity, small vessel disease, vascular contributions to cognitive impairment and dementia, VCID, white matter hyperintensity, white matter injury, MarkVCID Consortium, peak‐width skeletonized mean diffusivity, Genetics, Biological psychology
Abstract

IntroductionTo describe the protocol and findings of the instrumental validation of three imaging-based biomarker kits selected by the MarkVCID consortium: free water (FW) and peak width of skeletonized mean diffusivity (PSMD), both derived from diffusion tensor imaging (DTI), and white matter hyperintensity (WMH) volume derived from fluid attenuation inversion recovery and T1-weighted imaging.MethodsThe instrumental validation of imaging-based biomarker kits included inter-rater reliability among participating sites, test-retest repeatability, and inter-scanner reproducibility across three types of magnetic resonance imaging (MRI) scanners using intra-class correlation coefficients (ICC).ResultsThe three biomarkers demonstrated excellent inter-rater reliability (ICC >0.94, P-values 0.98, P-values 0.98, P-values

Published
2022

10. Effect of blood pressure-lowering agents on microvascular function in people with small vessel diseases (TREAT-SVDs): a multicentre, open-label, randomised, crossover trial

Author

Kopczak, Anna, Stringer, Michael S., van den Brink, Hilde, Kerkhofs, Danielle, Blair, Gordon W., van Dinther, Maud, Arteaga Reyes, Carmen, Jaime Garcia, Daniela, Onkenhout, Laurien, Wartolowska, Karolina A., Thrippleton, Michael J., Kampaite, Agniete, Duering, Marco, Staals, Julie, Lesnik-Oberstein, Saskia, Muir, Keith, Middeke, Martin, Norrving, Bo, Bousser, Marie-Germaine, Mansmann, Ulrich, Rothwell, Peter M., Doubal, Fergus N., van Oostenbrugge, Robert, Biessels, Geert Jan, Webb, Alastair J.S., Wardlaw, Joanna, Dichgans, Martin, André, Elisabeth, Kääb, Stefan, Anders, Hans-Joachim, Hack, Remco, Kaffe, Maria, Dewenter, Anna, Malik, Rainer, Stringer, Michael S, Blair, Gordon W, Reyes, Carmen Arteaga, Garcia, Daniela Jaime, Wartolowska, Karolina A, Thrippleton, Michael J, Muir, Keith W, Rothwell, Peter M, Doubal, Fergus N, Webb, Alastair J S, and Wardlaw, Joanna M

Published
2023
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11. White Matter Hyperintensity Volume and Poststroke Cognition: An Individual Patient Data Pooled Analysis of 9 Ischemic Stroke Cohort Studies

Author

de Kort, Floor A.S., Coenen, Mirthe, Weaver, Nick A., Kuijf, Hugo J., Aben, Hugo P., Bae, Hee-Joon, Bordet, Régis, Cammà, Guido, Chen, Christopher P.L.H., Dewenter, Anna, Duering, Marco, Fang, Rong, van der Giessen, Ruben S., Hamilton, Olivia K.L., Hilal, Saima, Huenges Wajer, Irene M.C., Kan, Cheuk Ni, Kim, Jonguk, Kim, Beom Joon, Köhler, Sebastian, de Kort, Paul L.M., Koudstaal, Peter J., Lim, Jae-Sung, Lopes, Renaud, Mok, Vincent C.T., Staals, Julie, Venketasubramanian, Narayanaswamy, Verhagen, Charlotte M., Verhey, Frans R.J., Wardlaw, Joanna M., Xu, Xin, Yu, Kyung-Ho, Biesbroek, J. Matthijs, and Biessels, Geert Jan

Published
2023
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12. Neuroimaging standards for research into small vessel disease—advances since 2013

Author

Duering, Marco, Biessels, Geert Jan, Brodtmann, Amy, Chen, Christopher, Cordonnier, Charlotte, de Leeuw, Frank-Erik, Debette, Stéphanie, Frayne, Richard, Jouvent, Eric, Rost, Natalia S, ter Telgte, Annemieke, Al-Shahi Salman, Rustam, Backes, Walter H, Bae, Hee-Joon, Brown, Rosalind, Chabriat, Hugues, De Luca, Alberto, deCarli, Charles, Dewenter, Anna, Doubal, Fergus N, Ewers, Michael, Field, Thalia S, Ganesh, Aravind, Greenberg, Steven, Helmer, Karl G, Hilal, Saima, Jochems, Angela C C, Jokinen, Hanna, Kuijf, Hugo, Lam, Bonnie Y K, Lebenberg, Jessica, MacIntosh, Bradley J, Maillard, Pauline, Mok, Vincent C T, Pantoni, Leonardo, Rudilosso, Salvatore, Satizabal, Claudia L, Schirmer, Markus D, Schmidt, Reinhold, Smith, Colin, Staals, Julie, Thrippleton, Michael J, van Veluw, Susanne J, Vemuri, Prashanthi, Wang, Yilong, Werring, David, Zedde, Marialuisa, Akinyemi, Rufus O, Del Brutto, Oscar H, Markus, Hugh S, Zhu, Yi-Cheng, Smith, Eric E, Dichgans, Martin, and Wardlaw, Joanna M

Published
2023
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13. Proceedings from the Albert Charitable Trust Inaugural Workshop on white matter and cognition in aging

Author

Sorond, Farzaneh A, Whitehead, Shawn, Arai, Ken, Arnold, Douglas, Carmichael, S Thomas, De Carli, Charles, Duering, Marco, Fornage, Myriam, Flores-Obando, Rafael E, Graff-Radford, Jonathan, Hamel, Edith, Hess, David C, Ihara, Massafumi, Jensen, Majken K, Markus, Hugh S, Montagne, Axel, Rosenberg, Gary, Shih, Andy Y, Smith, Eric E, Thiel, Alex, Tse, Kai Hei, Wilcock, Donna, and Barone, Frank

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Neurosciences, Aging, Alzheimer's Disease, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Brain Disorders, Behavioral and Social Science, Dementia, Neurodegenerative, Acquired Cognitive Impairment, Cognition, Cognitive Dysfunction, Dementia, Vascular, Humans, White Matter, Blood-brain barrier, Brain white matter, Myelin, Neurovascular, Oligovascular, Vascular cognitive impairment, Genetics, Clinical sciences
Abstract

This third in a series of vascular cognitive impairment (VCI) workshops, supported by "The Leo and Anne Albert Charitable Trust," was held from February 8 to 12 at the Omni Resort in Carlsbad, CA. This workshop followed the information gathered from the earlier two workshops suggesting that we focus more specifically on brain white matter in age-related cognitive impairment. The Scientific Program Committee (Frank Barone, Shawn Whitehead, Eric Smith, and Rod Corriveau) assembled translational, clinical, and basic scientists with unique expertise in acute and chronic white matter injury at the intersection of cerebrovascular and neurodegenerative etiologies. As in previous Albert Trust workshops, invited participants addressed key topics related to mechanisms of white matter injury, biomarkers of white matter injury, and interventions to prevent white matter injury and age-related cognitive decline. This report provides a synopsis of the presentations and discussions by the participants, including the existing knowledge gaps and the delineation of the next steps towards advancing our understanding of white matter injury and age-related cognitive decline. Workshop discussions and consensus resulted in action by The Albert Trust to (1) increase support from biannual to annual "White Matter and Cognition" workshops; (2) provide funding for two collaborative, novel research grants annually submitted by meeting participants; and (3) coordinate the formation of the "Albert Research Institute for White Matter and Cognition." This institute will fill a gap in white matter science, providing white matter and cognition communications, including annual updates from workshops and the literature and interconnecting with other Albert Trust scientific endeavors in cognition and dementia, and providing support for newly established collaborations between seasoned investigators and to the development of talented young investigators in the VCI-dementia (VCID) and white matter cognition arena.

Published
2020

14. The Meta VCI Map consortium for meta‐analyses on strategic lesion locations for vascular cognitive impairment using lesion‐symptom mapping: Design and multicenter pilot study

Author

Weaver, Nick A, Zhao, Lei, Biesbroek, J Matthijs, Kuijf, Hugo J, Aben, Hugo P, Bae, Hee‐Joon, Caballero, Miguel ÁA, Chappell, Francesca M, Chen, Christopher PLH, Dichgans, Martin, Duering, Marco, Georgakis, Marios K, van der Giessen, Ruben S, Gyanwali, Bibek, Hamilton, Olivia KL, Hilal, Saima, Hofe, Elise M vom, de Kort, Paul LM, Koudstaal, Peter J, Lam, Bonnie YK, Lim, Jae‐Sung, Makin, Stephen DJ, Mok, Vincent CT, Shi, Lin, Hernández, Maria C Valdés, Venketasubramanian, Narayanaswamy, Wardlaw, Joanna M, Wollenweber, Frank A, Wong, Adrian, Xin, Xu, consortium, Meta VCI Map, DeCarli, C, Fletcher, EA, Maillard, P, Barnes, J, Sudre, CH, Schott, JM, Ikram, MA, Papma, JM, Steketee, RME, Vernooij, MW, Bordet, R, Lopes, R, Huang, C‐W, Frayne, R, McCreary, CR, Smith, EE, group, Calgary Normative Study, Backes, W, Köhler, S, van Oostenbrugge, RJ, Staals, J, Verhey, F, Cheng, CY, Kalaria, RN, Werring, D, Hsu, JL, Huang, K‐L, van der Grond, J, Jukema, JW, van der Mast, RC, Nijboer, TCW, group, Framingham Heart Study, Yu, K‐H, group, The Dutch Parelsnoer Institute–Neurodegenerative diseases, Schmidt, R, Pirpamer, L, MacIntosh, BJ, Robertson, AD, de Leeuw, F‐E, Tuladhar, AM, Chaturvedi, N, Tillin, T, Brodaty, H, Sachdev, P, group, TABASCO, Barkhof, F, van der Flier, WM, Kappelle, LJ, and Biessels, Geert Jan

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Biomedical Imaging, Atherosclerosis, Clinical Research, Brain Disorders, Acquired Cognitive Impairment, Stroke, Neurosciences, Meta VCI Map consortium, Cerebrovascular disease, Consortium, Data harmonization, Lesion location, Lesion-symptom mapping, Small vessel disease, Support vector regression, Vascular cognitive impairment, Genetics, Biological psychology
Abstract

IntroductionThe Meta VCI Map consortium performs meta-analyses on strategic lesion locations for vascular cognitive impairment using lesion-symptom mapping. Integration of data from different cohorts will increase sample sizes, to improve brain lesion coverage and support comprehensive lesion-symptom mapping studies.MethodsCohorts with available imaging on white matter hyperintensities or infarcts and cognitive testing were invited. We performed a pilot study to test the feasibility of multicenter data processing and analysis and determine the benefits to lesion coverage.ResultsForty-seven groups have joined Meta VCI Map (stroke n = 7800 patients; memory clinic n = 4900; population-based n = 14,400). The pilot study (six ischemic stroke cohorts, n = 878) demonstrated feasibility of multicenter data integration (computed tomography/magnetic resonance imaging) and achieved marked improvement of lesion coverage.DiscussionMeta VCI Map will provide new insights into the relevance of vascular lesion location for cognitive dysfunction. After the successful pilot study, further projects are being prepared. Other investigators are welcome to join.

Published
2019

18. Strategic white matter hyperintensity locations associated with post-stroke cognitive impairment: a multicenter study in 1568 stroke patients

Author

Coenen, Mirthe, primary, de Kort, Floor A.S., additional, Weaver, Nick A., additional, Kuijf, Hugo J., additional, Aben, Hugo Paul, additional, Bae, Hee-Joon, additional, Bordet, Régis, additional, Chen, Christopher LH, additional, Dewenter, Anna, additional, Doeven, Thomas, additional, Dondaine, Thibaut, additional, Duering, Marco, additional, Fang, Rong, additional, van der Giessen, Ruben S, additional, Kim, Jonguk, additional, Kim, Beom Joon, additional, de Kort, Paul L.M., additional, Koudstaal, Peter, additional, Lee, Minwoo, additional, Lim, Jae-Sung, additional, Lopes, Renaud, additional, van Oostenbrugge, Robert J., additional, Staals, Julie, additional, Yu, Kyung-Ho, additional, Biessels, Geert Jan, additional, and Biesbroek, J. Matthijs, additional

Published
2024
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19. White matter diffusion alterations precede symptom onset in autosomal dominant Alzheimer’s disease

Author

Caballero, Miguel Ángel Araque, Suárez-Calvet, Marc, Duering, Marco, Franzmeier, Nicolai, Benzinger, Tammie, Fagan, Anne M, Bateman, Randall J, Jack, Clifford R, Levin, Johannes, Dichgans, Martin, Jucker, Mathias, Karch, Celeste, Masters, Colin L, Morris, John C, Weiner, Michael, Rossor, Martin, Fox, Nick C, Lee, Jae-Hong, Salloway, Stephen, Danek, Adrian, Goate, Alison, Yakushev, Igor, Hassenstab, Jason, Schofield, Peter R, Haass, Christian, and Ewers, Michael

Subjects
Health Services and Systems, Health Sciences, Neurosciences, Dementia, Biomedical Imaging, Clinical Research, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Acquired Cognitive Impairment, Brain Disorders, Alzheimer's Disease, Neurodegenerative, Aging, 2.1 Biological and endogenous factors, Aetiology, Neurological, Adult, Alzheimer Disease, Brain, Diffusion Tensor Imaging, Female, Humans, Male, Middle Aged, White Matter, Alzheimer's disease, autosomal dominant, white matter, diffusion tensor imaging, TREM2, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery, Biomedical and clinical sciences, Health sciences, Psychology
Abstract

White matter alterations are present in the majority of patients with Alzheimer's disease type dementia. However, the spatiotemporal pattern of white matter changes preceding dementia symptoms in Alzheimer's disease remains unclear, largely due to the inherent diagnostic uncertainty in the preclinical phase and increased risk of confounding age-related vascular disease and stroke in late-onset Alzheimer's disease. In early-onset autosomal-dominantly inherited Alzheimer's disease, participants are destined to develop dementia, which provides the opportunity to assess brain changes years before the onset of symptoms, and in the absence of ageing-related vascular disease. Here, we assessed mean diffusivity alterations in the white matter in 64 mutation carriers compared to 45 non-carrier family non-carriers. Using tract-based spatial statistics, we mapped the interaction of mutation status by estimated years from symptom onset on mean diffusivity. For major atlas-derived fibre tracts, we determined the earliest time point at which abnormal mean diffusivity changes in the mutation carriers were detectable. Lastly, we assessed the association between mean diffusivity and cerebrospinal fluid biomarkers of amyloid, tau, phosphorylated-tau, and soluble TREM2, i.e. a marker of microglia activity. Results showed a significant interaction of mutations status by estimated years from symptom onset, i.e. a stronger increase of mean diffusivity, within the posterior parietal and medial frontal white matter in mutation carriers compared with non-carriers. The earliest increase of mean diffusivity was observed in the forceps major, forceps minor and long projecting fibres-many connecting default mode network regions-between 5 to 10 years before estimated symptom onset. Higher mean diffusivity in fibre tracts was associated with lower grey matter volume in the tracts' projection zones. Global mean diffusivity was correlated with lower cerebrospinal fluid levels of amyloid-β1-42 but higher levels of tau, phosphorylated-tau and soluble TREM2. Together, these results suggest that regionally selective white matter degeneration occurs years before the estimated symptom onset. Such white matter alterations are associated with primary Alzheimer's disease pathology and microglia activity in the brain.

Published
2018

26. Left frontal hub connectivity delays cognitive impairment in autosomal-dominant and sporadic Alzheimer’s disease

Author

Franzmeier, Nicolai, Düzel, Emrah, Jessen, Frank, Buerger, Katharina, Levin, Johannes, Duering, Marco, Dichgans, Martin, Haass, Christian, Suárez-Calvet, Marc, Fagan, Anne M, Paumier, Katrina, Benzinger, Tammie, Masters, Colin L, Morris, John C, Perneczky, Robert, Janowitz, Daniel, Catak, Cihan, Wolfsgruber, Steffen, Wagner, Michael, Teipel, Stefan, Kilimann, Ingo, Ramirez, Alfredo, Rossor, Martin, Jucker, Mathias, Chhatwal, Jasmeer, Spottke, Annika, Boecker, Henning, Brosseron, Frederic, Falkai, Peter, Fliessbach, Klaus, Heneka, Michael T, Laske, Christoph, Nestor, Peter, Peters, Oliver, Fuentes, Manuel, Menne, Felix, Priller, Josef, Spruth, Eike J, Franke, Christiana, Schneider, Anja, Kofler, Barbara, Westerteicher, Christine, Speck, Oliver, Wiltfang, Jens, Bartels, Claudia, Caballero, Miguel Ángel Araque, Metzger, Coraline, Bittner, Daniel, Weiner, Michael, Lee, Jae-Hong, Salloway, Stephen, Danek, Adrian, Goate, Alison, Schofield, Peter R, Bateman, Randall J, and Ewers, Michael

Subjects
Clinical Trials and Supportive Activities, Brain Disorders, Aging, Basic Behavioral and Social Science, Dementia, Neurosciences, Behavioral and Social Science, Acquired Cognitive Impairment, Clinical Research, Alzheimer's Disease, Neurodegenerative, Biomedical Imaging, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Aetiology, 2.1 Biological and endogenous factors, Neurological, Adult, Alzheimer Disease, Amyloid beta-Protein Precursor, Brain Mapping, Cognitive Dysfunction, Female, Frontal Lobe, Functional Laterality, Humans, Imaging, Three-Dimensional, Magnetic Resonance Imaging, Male, Middle Aged, Mutation, Nerve Net, Presenilin-1, Presenilin-2, Alzheimer's disease, cognitive reserve, resting state connectivity, memory, dementia biomarkers, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery
Abstract

Patients with Alzheimer's disease vary in their ability to sustain cognitive abilities in the presence of brain pathology. A major open question is which brain mechanisms may support higher reserve capacity, i.e. relatively high cognitive performance at a given level of Alzheimer's pathology. Higher functional MRI-assessed functional connectivity of a hub in the left frontal cortex is a core candidate brain mechanism underlying reserve as it is associated with education (i.e. a protective factor often associated with higher reserve) and attenuated cognitive impairment in prodromal Alzheimer's disease. However, no study has yet assessed whether such hub connectivity of the left frontal cortex supports reserve throughout the evolution of pathological brain changes in Alzheimer's disease, including the presymptomatic stage when cognitive decline is subtle. To address this research gap, we obtained cross-sectional resting state functional MRI in 74 participants with autosomal dominant Alzheimer's disease, 55 controls from the Dominantly Inherited Alzheimer's Network and 75 amyloid-positive elderly participants, as well as 41 amyloid-negative cognitively normal elderly subjects from the German Center of Neurodegenerative Diseases multicentre study on biomarkers in sporadic Alzheimer's disease. For each participant, global left frontal cortex connectivity was computed as the average resting state functional connectivity between the left frontal cortex (seed) and each voxel in the grey matter. As a marker of disease stage, we applied estimated years from symptom onset in autosomal dominantly inherited Alzheimer's disease and cerebrospinal fluid tau levels in sporadic Alzheimer's disease cases. In both autosomal dominant and sporadic Alzheimer's disease patients, higher levels of left frontal cortex connectivity were correlated with greater education. For autosomal dominant Alzheimer's disease, a significant left frontal cortex connectivity × estimated years of onset interaction was found, indicating slower decline of memory and global cognition at higher levels of connectivity. Similarly, in sporadic amyloid-positive elderly subjects, the effect of tau on cognition was attenuated at higher levels of left frontal cortex connectivity. Polynomial regression analysis showed that the trajectory of cognitive decline was shifted towards a later stage of Alzheimer's disease in patients with higher levels of left frontal cortex connectivity. Together, our findings suggest that higher resilience against the development of cognitive impairment throughout the early stages of Alzheimer's disease is at least partially attributable to higher left frontal cortex-hub connectivity.

Published
2018

28. Long-Term Brain Structure and Cognition Following Bariatric Surgery

Author

Custers, Emma, primary, Vreeken, Debby, additional, Kleemann, Robert, additional, Kessels, Roy P. C., additional, Duering, Marco, additional, Brouwer, Jonna, additional, Aufenacker, Theo J., additional, Witteman, Bart P. L., additional, Snabel, Jessica, additional, Gart, Eveline, additional, Mutsaerts, Henk J. M. M., additional, Wiesmann, Maximilian, additional, Hazebroek, Eric J., additional, and Kiliaan, Amanda J., additional

Published
2024
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29. Characterization of Vasogenic and Cytotoxic Brain Edema Formation After Experimental Traumatic Brain Injury by Free Water Diffusion Magnetic Resonance Imaging

Author

Hu, Senbin, primary, Exner, Carina, additional, Sienel, Rebecca Isabella, additional, When, Antonia Clarissa, additional, Seker, Fatma Burcu, additional, Boldoczki, Fanni Magdane, additional, Guo, Yinghuimin, additional, Duering, Marco, additional, Pasternak, Ofer, additional, Plesnila, Nikolaus, additional, and Schwarzmaier, Susanne M., additional

Published
2024
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31. Imaging neurovascular, endothelial and structural integrity in preparation to treat small vessel diseases. The INVESTIGATE-SVDs study protocol. Part of the SVDs@Target project

Author

Blair, Gordon W., Stringer, Michael S., Thrippleton, Michael J., Chappell, Francesca M., Shuler, Kirsten, Hamilton, Iona, Garcia, Daniela Jaime, Doubal, Fergus N., Kopczak, Anna, Duering, Marco, Ingrisch, Michael, Kerkhofs, Danielle, Staals, Julie, van den Brink, Hilde, Arts, Tine, Backes, Walter H, van Oostenbrugge, Robert, Biessels, Geert Jan, Dichgans, Martin, and Wardlaw, Joanna M.

Published
2021
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32. Zooming in on cerebral small vessel function in small vessel diseases with 7T MRI: Rationale and design of the “ZOOM@SVDs” study

Author

van den Brink, Hilde, Kopczak, Anna, Arts, Tine, Onkenhout, Laurien, Siero, Jeroen C.W., Zwanenburg, Jaco J.M., Duering, Marco, Blair, Gordon W., Doubal, Fergus N., Stringer, Michael S., Thrippleton, Michael J., Kuijf, Hugo J., de Luca, Alberto, Hendrikse, Jeroen, Wardlaw, Joanna M., Dichgans, Martin, and Biessels, Geert Jan

Published
2021
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33. Left frontal cortex connectivity underlies cognitive reserve in prodromal Alzheimer disease

Author

Franzmeier, Nicolai, Duering, Marco, Weiner, Michael, Dichgans, Martin, and Ewers, Michael

Subjects
Prevention, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, Brain Disorders, Aging, Neurodegenerative, Clinical Research, Neurosciences, Biomedical Imaging, Acquired Cognitive Impairment, Alzheimer's Disease, 2.1 Biological and endogenous factors, Aetiology, Neurological, Alzheimer Disease, Chi-Square Distribution, Cognition Disorders, Cognitive Reserve, Epilepsy, Female, Fluorodeoxyglucose F18, Frontal Lobe, Functional Laterality, Humans, Magnetic Resonance Imaging, Male, Nerve Net, Neuropsychological Tests, Oxygen, Positron-Emission Tomography, Prodromal Symptoms, Alzheimer's Disease Neuroimaging Initiative, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract

ObjectiveTo test whether higher global functional connectivity of the left frontal cortex (LFC) in Alzheimer disease (AD) is associated with more years of education (a proxy of cognitive reserve [CR]) and mitigates the association between AD-related fluorodeoxyglucose (FDG)-PET hypometabolism and episodic memory.MethodsForty-four amyloid-PET-positive patients with amnestic mild cognitive impairment (MCI-Aβ+) and 24 amyloid-PET-negative healthy controls (HC) were included. Voxel-based linear regression analyses were used to test the association between years of education and FDG-PET in MCI-Aβ+, controlled for episodic memory performance. Global LFC (gLFC) connectivity was computed through seed-based resting-state fMRI correlations between the LFC (seed) and each voxel in the gray matter. In linear regression analyses, education as a predictor of gLFC connectivity and the interaction of gLFC connectivity × FDG-PET hypometabolism on episodic memory were tested.ResultsFDG-PET metabolism in the precuneus was reduced in MCI-Aβ+ compared to HC (p = 0.028), with stronger reductions observed in MCI-Aβ+ with more years of education (p = 0.006). In MCI-Aβ+, higher gLFC connectivity was associated with more years of education (p = 0.021). At higher levels of gLFC connectivity, the association between precuneus FDG-PET hypometabolism and lower memory performance was attenuated (p = 0.027).ConclusionsHigher gLFC connectivity is a functional substrate of CR that helps to maintain episodic memory relatively well in the face of emerging FDG-PET hypometabolism in early-stage AD.

Published
2017

34. Prevalence and Significance of the Vessel-Cluster Sign on Susceptibility-Weighted Imaging in Patients With Severe Small Vessel Disease

Author

Rudilosso, Salvatore, Chui, Ernest, Stringer, Michael S., Thrippleton, Michael, Chappell, Francesca, Blair, Gordon W., Garcia, Daniela Jaime, Doubal, Fergus, Hamilton, Iona, Kopczak, Anna, Ingrisch, Michael, Kerkhofs, Danielle, Backes, Walter H., Staals, Julie, van Oostenbrugge, Robert, Duering, Marco, Dichgans, Martin, and Wardlaw, Joanna M.

Published
2022
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35. The BDNFVal66Met SNP modulates the association between beta-amyloid and hippocampal disconnection in Alzheimer’s disease

Author

Franzmeier, Nicolai, Ren, Jinyi, Damm, Alexander, Monté-Rubio, Gemma, Boada, Mercè, Ruiz, Agustín, Ramirez, Alfredo, Jessen, Frank, Düzel, Emrah, Rodríguez Gómez, Octavio, Benzinger, Tammie, Goate, Alison, Karch, Celeste M., Fagan, Anne M., McDade, Eric, Buerger, Katharina, Levin, Johannes, Duering, Marco, Dichgans, Martin, Suárez-Calvet, Marc, Haass, Christian, Gordon, Brian A., Lim, Yen Ying, Masters, Colin L., Janowitz, Daniel, Catak, Cihan, Wolfsgruber, Steffen, Wagner, Michael, Milz, Esther, Moreno-Grau, Sonia, Teipel, Stefan, Grothe, Michel J, Kilimann, Ingo, Rossor, Martin, Fox, Nick, Laske, Christoph, Chhatwal, Jasmeer, Falkai, Peter, Perneczky, Robert, Lee, Jae-Hong, Spottke, Annika, Boecker, Henning, Brosseron, Frederic, Fliessbach, Klaus, Heneka, Michael T., Nestor, Peter, Peters, Oliver, Fuentes, Manuel, Menne, Felix, Priller, Josef, Spruth, Eike J., Franke, Christiana, Schneider, Anja, Westerteicher, Christine, Speck, Oliver, Wiltfang, Jens, Bartels, Claudia, Araque Caballero, Miguel Ángel, Metzger, Coraline, Bittner, Daniel, Salloway, Stephen, Danek, Adrian, Hassenstab, Jason, Yakushev, Igor, Schofield, Peter R., Morris, John C., Bateman, Randall J., and Ewers, Michael

Published
2021
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37. Consensus statement for diagnosis of subcortical small vessel disease

Author

Rosenberg, Gary A, Wallin, Anders, Wardlaw, Joanna M, Markus, Hugh S, Montaner, Joan, Wolfson, Leslie, Iadecola, Costantino, Zlokovic, Berislav V, Joutel, Anne, Dichgans, Martin, Duering, Marco, Schmidt, Reinhold, Korczyn, Amos D, Grinberg, Lea T, Chui, Helena C, and Hachinski, Vladimir

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Brain Disorders, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Acquired Cognitive Impairment, Dementia, Vascular Cognitive Impairment/Dementia, Biomedical Imaging, Rare Diseases, Neurosciences, Alzheimer's Disease Related Dementias (ADRD), Aging, Blood-Brain Barrier, Capillary Permeability, Dementia, Vascular, Humans, Leukoaraiosis, Microvessels, Binswanger's disease, blood-brain barrier permeability, cerebrospinal fluid, inflammation, leukoaraiosis
Abstract

Vascular cognitive impairment (VCI) is the diagnostic term used to describe a heterogeneous group of sporadic and hereditary diseases of the large and small blood vessels. Subcortical small vessel disease (SVD) leads to lacunar infarcts and progressive damage to the white matter. Patients with progressive damage to the white matter, referred to as Binswanger's disease (BD), constitute a spectrum from pure vascular disease to a mixture with neurodegenerative changes. Binswanger's disease patients are a relatively homogeneous subgroup with hypoxic hypoperfusion, lacunar infarcts, and inflammation that act synergistically to disrupt the blood-brain barrier (BBB) and break down myelin. Identification of this subgroup can be facilitated by multimodal disease markers obtained from clinical, cerebrospinal fluid, neuropsychological, and imaging studies. This consensus statement identifies a potential set of biomarkers based on underlying pathologic changes that could facilitate diagnosis and aid patient selection for future collaborative treatment trials.

Published
2016

38. Brain-derived Tau for Monitoring Brain Injury in Acute Ischemic Stroke

Author

Vlegels, Naomi, primary, Gonzalez-Ortiz, Fernando, additional, Knuth, Nicoló Luca, additional, Khalifeh, Nada, additional, Gesierich, Benno, additional, Müller, Franziska, additional, Müller, Philipp, additional, Klein, Matthias, additional, Dimitriadis, Konstantinos, additional, Franzmeier, Nicolai, additional, Liebig, Thomas, additional, Duering, Marco, additional, Reidler, Paul, additional, Dichgans, Martin, additional, Karikari, Thomas K., additional, Blennow, Kaj, additional, and Tiedt, Steffen, additional

Published
2023
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39. Spatial distributions of white matter hyperintensities on brain MRI: a pooled analysis of individual participant data from 11 memory clinic cohorts

Author

Coenen, Mirthe, primary, Jan Biessels, Geert, additional, DeCarli, Charles, additional, Fletcher, Evan F., additional, Maillard, Pauline M., additional, Barkhof, Frederik, additional, Barnes, Josephine, additional, Benke, Thomas, additional, Boomsma, Jooske M.F., additional, P.L.H. Chen, Christopher, additional, Dal-Bianco, Peter, additional, Dewenter, Anna, additional, Duering, Marco, additional, Enzinger, Christian, additional, Ewers, Michael, additional, Exalto, Lieza G., additional, Franzmeier, Nicolai, additional, Groeneveld, Onno, additional, Hilal, Saima, additional, Hofer, Edith, additional, Koek, Huiberdina L., additional, Maier, Andrea B., additional, McCreary, Cheryl R., additional, Papma, Janne M., additional, Paterson, Ross W., additional, Pijnenburg, Yolande A.L., additional, Rubinski, Anna, additional, Schmidt, Reinhold, additional, Schott, Jonathan M., additional, Slattery, Catherine F., additional, Smith, Eric E., additional, Sudre, Carole H., additional, Steketee, Rebecca M.E., additional, van den Berg, Esther, additional, van der Flier, Wiesje M., additional, Venketasubramanian, Narayanaswamy, additional, Vernooij, Meike W., additional, Wolters, Frank J., additional, Xin, Xu, additional, Matthijs Biesbroek, J., additional, and Kuijf, Hugo J., additional

Published
2023
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42. The Meta VCI Map consortium for meta-analyses on strategic lesion locations for vascular cognitive impairment using lesion-symptom mapping: Design and multicenter pilot study

Author

DeCarli, C., Fletcher, E.A., Maillard, P., Barnes, J., Sudre, C.H., Schott, J.M., Ikram, M.A., Papma, J.M., Steketee, R.M.E., Vernooij, M.W., Bordet, R., Lopes, R., Huang, C.-W., Frayne, R., McCreary, C.R., Smith, E.E., Backes, W., Köhler, S., van Oostenbrugge, R.J., Staals, J., Verhey, F., Cheng, C.Y., Kalaria, R.N., Werring, D., Hsu, J.L., Huang, K.-L., van der Grond, J., Jukema, J.W., van der Mast, R.C., Nijboer, T.C.W., Yu, K.-H., Schmidt, R., Pirpamer, L., MacIntosh, B.J., Robertson, A.D., de Leeuw, F.-E., Tuladhar, A.M., Chaturvedi, N., Tillin, T., Brodaty, H., Sachdev, P., Barkhof, F., van der Flier, W.M., Kappelle, L.J., Weaver, Nick A., Zhao, Lei, Biesbroek, J. Matthijs, Kuijf, Hugo J., Aben, Hugo P., Bae, Hee-Joon, Caballero, Miguel Á.A., Chappell, Francesca M., Chen, Christopher P.L.H., Dichgans, Martin, Duering, Marco, Georgakis, Marios K., van der Giessen, Ruben S., Gyanwali, Bibek, Hamilton, Olivia K.L., Hilal, Saima, vom Hofe, Elise M., de Kort, Paul L.M., Koudstaal, Peter J., Lam, Bonnie Y.K., Lim, Jae-Sung, Makin, Stephen D.J., Mok, Vincent C.T., Shi, Lin, Valdés Hernández, Maria C., Venketasubramanian, Narayanaswamy, Wardlaw, Joanna M., Wollenweber, Frank A., Wong, Adrian, Xin, Xu, and Biessels, Geert Jan

Published
2019
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43. Harmonizing brain magnetic resonance imaging methods for vascular contributions to neurodegeneration

Author

Smith, Eric E., Biessels, Geert Jan, De Guio, François, de Leeuw, Frank Erik, Duchesne, Simon, Düring, Marco, Frayne, Richard, Ikram, M. Arfan, Jouvent, Eric, MacIntosh, Bradley J., Thrippleton, Michael J., Vernooij, Meike W., Adams, Hieab, Backes, Walter H., Ballerini, Lucia, Black, Sandra E., Chen, Christopher, Corriveau, Rod, DeCarli, Charles, Greenberg, Steven M., Gurol, M. Edip, Ingrisch, Michael, Job, Dominic, Lam, Bonnie Y.K., Launer, Lenore J., Linn, Jennifer, McCreary, Cheryl R., Mok, Vincent C.T., Pantoni, Leonardo, Pike, G. Bruce, Ramirez, Joel, Reijmer, Yael D., Romero, Jose Rafael, Ropele, Stefan, Rost, Natalia S., Sachdev, Perminder S., Scott, Christopher J.M., Seshadri, Sudha, Sharma, Mukul, Sourbron, Steven, Steketee, Rebecca M.E., Swartz, Richard H., van Oostenbrugge, Robert, van Osch, Matthias, van Rooden, Sanneke, Viswanathan, Anand, Werring, David, Dichgans, Martin, and Wardlaw, Joanna M.

Published
2019
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46. Safety and efficacy of epigallocatechin gallate in multiple system atrophy (PROMESA): a randomised, double-blind, placebo-controlled trial

Author

André, Elisabeth, Blankenstein, Christiane, Canelo, Monica, Düring, Marco, Ebentheuer, Jens, Fricke, Christopher, Gerbes, Alexander, Groiss, Stefan, Gruber, Doreen, Hartmann, Christian, Kirchner, Thomas, Kroneberg, Daniel, Kunz, Martin, Lorenzl, Stefan, Moldovan, Alexia, Noda, Anna, Pape, Heidi, Respondek, Gesine, Schäffer, Eva, Schneider, Martina, Schnitzler, Alfons, Schulz-Schaeffer, Walter, Schwarz, Johannes, Skowronek, Cornelia, Storch, Alexander, Tadic, Vera, Vadász, Dávid, Zimmermann, Benno, Levin, Johannes, Maaß, Sylvia, Schuberth, Madeleine, Giese, Armin, Oertel, Wolfgang H, Poewe, Werner, Trenkwalder, Claudia, Wenning, Gregor K, Mansmann, Ulrich, Südmeyer, Martin, Eggert, Karla, Mollenhauer, Brit, Lipp, Axel, Löhle, Matthias, Classen, Joseph, Münchau, Alexander, Kassubek, Jan, Gandor, Florin, Berg, Daniela, Egert-Schwender, Silvia, Eberhardt, Cornelia, Paul, Friedemann, Bötzel, Kai, Ertl-Wagner, Birgit, Huppertz, Hans-Jürgen, Ricard, Ingrid, and Höglinger, Günter U

Published
2019
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50. Structural Network Efficiency Predicts Conversion to Incident Parkinsonism in Patients With Cerebral Small Vessel Disease.

Author

Cai, Mengfei, Jacob, Mina A, Marques, José, Norris, David G, Duering, Marco, Esselink, Rianne A J, Zhang, Yuhu, Leeuw, Frank-Erik de, and Tuladhar, Anil M

Subjects
CEREBRAL small vessel diseases, PARKINSONIAN disorders, PARKINSON'S disease, MAGNETIC resonance imaging
Abstract

Background To investigate whether structural network disconnectivity is associated with parkinsonian signs and their progression, as well as with an increased risk of incident parkinsonism. Methods In a prospective cohort (Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort study) consisting of 293 participants with small vessel disease (SVD), we assessed parkinsonian signs and incident parkinsonism over an 8-year follow-up. In addition, we reconstructed the white matter network followed by graph-theoretical analyses to compute the network metrics. Conventional magnetic resonance imaging markers for SVD were assessed. Results We included 293 patients free of parkinsonism at baseline (2011), with a mean age 68.8 (standard deviation [ SD ] 8.4) years, and 130 (44.4%) were men. Nineteen participants (6.5%) developed parkinsonism during a median (SD) follow-up time of 8.3 years. Compared with participants without parkinsonism, those with all-cause parkinsonism had higher Unified Parkinson's Disease Rating scale (UPDRS) scores and lower global efficiency at baseline. Baseline global efficiency was associated with UPDRS motor scores in 2011 (β = −0.047, p  < .001) and 2015 (β = −0.84, p  < .001), as well as with the changes in UPDRS scores during the 4-year follow-up (β = −0.63, p  = .004). In addition, at the regional level, we identified an inter-hemispheric disconnected network associated with an increased UPDRS motor score. Besides, lower global efficiency was associated with an increased risk of all-cause and vascular parkinsonism independent of SVD markers. Conclusions Our findings suggest that global network efficiency is associated with a gradual decline in motor performance, ultimately leading to incident parkinsonism in the elderly with SVD. Global network efficiency may have the added value to serve as a useful marker to capture changes in motor signs. [ABSTRACT FROM AUTHOR]

Published
2024
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