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5. Level I PD‐MCI Using Global Cognitive Tests and the Risk for Parkinson's Disease Dementia

Author

Boel, Judith A, de Bie, Rob MA, Schmand, Ben A, Dalrymple‐Alford, John C, Marras, Connie, Adler, Charles H, Goldman, Jennifer G, Tröster, Alexander I, Burn, David J, Litvan, Irene, Geurtsen, Gert J, Bernard, Bryan, Stebbins, Glenn, Filoteo, J Vincent, Weintraub, Daniel, Caviness, John N, Belden, Christine, Zabetian, Cyrus P, Cholerton, Brenna A, Huang, Xuemei, Eslinger, Paul J, Leverenz, James B, Duff‐Canning, Sarah, Farrer, Matt, Anderson, Tim J, Myall, Daniel J, Naismith, Sharon L, Lewis, Simon JG, Halliday, Glenda M, Wu, Ruey‐Meei, Williams‐Gray, Caroline H, Breen, David P, Barker, Roger A, Yarnall, Alison J, Klein, Martin, Mollenhauer, Brit, Trenkwalder, Claudia, Kulisevsky, Jaime, Pagonabarraga, Javier, Gasca‐Salas, Carmen, Rodriguez‐Oroz, Maria C, Junque, Carme, Segura, Barbara, Barone, Paolo, Santangelo, Gabriella, Cammisuli, Davide M, Biundo, Roberta, Antonini, Angelo, Weis, Luca, Pedersen, Kenn Freddy, and Alves, Guido

Subjects
Acquired Cognitive Impairment, Neurodegenerative, Neurosciences, Parkinson's Disease, Dementia, Clinical Research, Aging, Brain Disorders, Neurological, dementia, mild cognitive impairment, global cognitive tests, Parkinson's disease, diagnostic accuracy, MDS Study Group Mild Cognitive Impairment in Parkinson's Disease
Abstract

BackgroundThe criteria for PD-MCI allow the use of global cognitive tests. Their predictive value for conversion from PD-MCI to PDD, especially compared to comprehensive neuropsychological assessment, is unknown.MethodsThe MDS PD-MCI Study Group combined four datasets containing global cognitive tests as well as a comprehensive neuropsychological assessment to define PD-MCI (n = 467). Risk for developing PDD was examined using a Cox model. Global cognitive tests were compared to neuropsychological test batteries (Level I&II) in determining risk for PDD.ResultsPD-MCI based on a global cognitive test (MMSE or MoCA) increases the hazard for developing PDD (respectively HR = 2.57, P = 0.001; HR = 4.14, P =

Published
2022

8. Lack of Association Between GBA Mutations and Motor Complications in European and American Parkinson’s Disease Cohorts

Author

Maple-Grødem, Jodi, Paul, Kimberly C, Dalen, Ingvild, Ngo, Kathie J, Wong, Darice, Macleod, Angus D, Counsell, Carl E, Bäckström, David, Forsgren, Lars, Tysnes, Ole-Bjørn, Kusters, Cynthia DJ, Fogel, Brent L, Bronstein, Jeff M, Ritz, Beate, and Alves, Guido

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Neurodegenerative, Neurosciences, Aging, Parkinson's Disease, Clinical Research, Brain Disorders, Aetiology, 2.1 Biological and endogenous factors, Neurological, Dyskinesias, Glucosylceramidase, Humans, Levodopa, Mental Status and Dementia Tests, Mutation, Parkinson Disease, GBA, Parkinson's disease, motor complications, dyskinesias, motor fluctuations, Parkinson’s disease, Biochemistry and Cell Biology
Abstract

BackgroundMotor complications are a consequence of the chronic dopaminergic treatment of Parkinson's disease (PD) and include levodopa-induced dyskinesia (LIDs) and motor fluctuations (MF). Currently, evidence is on lacking whether patients with GBA-associated PD differ in their risk of developing motor complications compared to the general PD population.ObjectiveTo evaluate the association of GBA carrier status with the development of LIDS and MFs from early PD.MethodsMotor complications were recorded prospectively in 884 patients with PD from four longitudinal cohorts using part IV of the UPDRS or MDS-UPDRS. Subjects were followed for up to 11 years and the associations of GBA mutations with the development of motor complications were assessed using parametric accelerated failure time models.ResultsIn 439 patients from Europe, GBA mutations were detected in 53 (12.1%) patients and a total of 168 cases of LIDs and 258 cases of MF were observed. GBA carrier status was not associated with the time to develop LIDs (HR 0.78, 95%CI 0.47 to 1.26, p = 0.30) or MF (HR 1.19, 95%CI 0.84 to 1.70, p = 0.33). In the American cohorts, GBA mutations were detected in 36 (8.1%) patients and GBA carrier status was also not associated with the progression to LIDs (HR 1.08, 95%CI 0.55 to 2.14, p = 0.82) or MF (HR 1.22, 95%CI 0.74 to 2.04, p = 0.43).ConclusionThis study does not provide evidence that GBA-carrier status is associated with a higher risk of developing motor complications. Publication of studies with null results is vital to develop an accurate summary of the clinical features that impact patients with GBA-associated PD.

Published
2021

9. Genetic risk scores and hallucinations in patients with Parkinson disease

Author

Kusters, Cynthia DJ, Paul, Kimberly C, Duarte Folle, Aline, Keener, Adrienne M, Bronstein, Jeff M, Dobricic, Valerija, Tysnes, Ole-Bjørn, Bertram, Lars, Alves, Guido, Sinsheimer, Janet S, Lill, Christina M, Maple-Grødem, Jodi, and Ritz, Beate R

Subjects
Biological Sciences, Genetics, Parkinson's Disease, Dementia, Mental Health, Acquired Cognitive Impairment, Neurosciences, Neurodegenerative, Clinical Research, Serious Mental Illness, Brain Disorders, Aging, Schizophrenia, Aetiology, 2.1 Biological and endogenous factors, Neurological, Clinical sciences
Abstract

ObjectiveWe examine the hypothesized overlap of genetic architecture for Alzheimer disease (AD), schizophrenia (SZ), and Parkinson disease (PD) through the use of polygenic risk scores (PRSs) with the occurrence of hallucinations in PD.MethodsWe used 2 population-based studies (ParkWest, Norway, and Parkinson's Environment and Gene, USA) providing us with 399 patients with PD with European ancestry and a PD diagnosis after age 55 years to assess the associations between 4 PRSs and hallucinations after 5 years of mean disease duration. Based on the existing genome-wide association study of other large consortia, 4 PRSs were created: one each using AD, SZ, and PD cohorts and another PRS for height, which served as a negative control.ResultsA higher prevalence of hallucinations was observed with each SD increase of the AD-PRS (odds ratio [OR]: 1.37, 95% confidence interval [CI]: 1.03-1.83). This effect was mainly driven by APOE (OR: 1.92, 95% CI: 1.14-3.22). In addition, a suggestive decrease and increase, respectively, in hallucination prevalence were observed with the SZ-PRS and the PD-PRS (OR: 0.77, 95% CI: 0.59-1.01; and OR: 1.29, 95% CI: 0.95-1.76, respectively). No association was observed with the height PRS.ConclusionsThese results suggest that mechanisms for hallucinations in PD may in part be driven by the same genetic architecture that leads to cognitive decline in AD, especially by APOE.

Published
2020

15. Genome-wide survival study identifies a novel synaptic locus and polygenic score for cognitive progression in Parkinson’s disease

Author

Liu, Ganqiang, Peng, Jiajie, Liao, Zhixiang, Locascio, Joseph J., Corvol, Jean-Christophe, Zhu, Frank, Dong, Xianjun, Maple-Grødem, Jodi, Campbell, Meghan C., Elbaz, Alexis, Lesage, Suzanne, Brice, Alexis, Mangone, Graziella, Growdon, John H., Hung, Albert Y., Schwarzschild, Michael A., Hayes, Michael T., Wills, Anne-Marie, Herrington, Todd M., Ravina, Bernard, Shoulson, Ira, Taba, Pille, Kõks, Sulev, Beach, Thomas G., Cormier-Dequaire, Florence, Alves, Guido, Tysnes, Ole-Bjørn, Perlmutter, Joel S., Heutink, Peter, Amr, Sami S., van Hilten, Jacobus J., Kasten, Meike, Mollenhauer, Brit, Trenkwalder, Claudia, Klein, Christine, Barker, Roger A., Williams-Gray, Caroline H., Marinus, Johan, and Scherzer, Clemens R.

Published
2021
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17. Fatigue in Parkinson's Disease: A Proteomic Study of Cerebrospinal Fluid

Author

Eidem, Live Egeland, primary, Birkeland, Even, additional, Austdal, Marie, additional, Bårdsen, Kjetil, additional, Lange, Johannes, additional, Alves, Guido, additional, Berven, Frode, additional, Nilsen, Mari Mæland, additional, Herlofson, Karen, additional, Tysnes, Ole‐Bjørn, additional, and Omdal, Roald, additional

Published
2024
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25. Mitochondrial complex I deficiency stratifies idiopathic Parkinson’s disease

Author

Flønes, Irene H, primary, Toker, Lilah, additional, Sandnes, Dagny Ann, additional, Castelli, Martina, additional, Mostafavi, Sepideh, additional, Lura, Njål, additional, Shadad, Omnia, additional, Fernandez-Vizarra, Erika, additional, Painous, Cèlia, additional, Pérez-Soriano, Alexandra, additional, Compta, Yaroslau, additional, Molina-Porcel, Laura, additional, Alves, Guido, additional, Tysnes, Ole-Bjørn, additional, Dölle, Christian, additional, Nido, Gonzalo S, additional, and Tzoulis, Charalampos, additional

Published
2023
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28. Contributors

Author

Alam, Gelareh, primary, Albino, C.M., additional, Almeida, Quincy J., additional, Alves, Guido W., additional, Anderton, Ryan S., additional, Andrzejewski, Kryspin, additional, Annesley, Sarah J., additional, Aufschnaiter, Andreas, additional, Ayres, Annelise, additional, Berge-Seidl, Victoria, additional, Birba, Agustina, additional, Bocanegra, Yamile, additional, Broderick, Patricia A., additional, Bubacco, Luigi, additional, Büttner, Sabrina, additional, Candeias, Emanuel, additional, Cardoso, Sandra Morais, additional, Chagraoui, Abdeslam, additional, Chiu, Wei-Hua, additional, Cogo, Susanna, additional, Corrente, José Eduardo, additional, Costa, Helena, additional, De Deurwaerdère, Philippe, additional, de Souza, Hellio Danny Nóbrega, additional, Dorieux, Flávia W.C., additional, Esteves, Ana Raquel, additional, Fagotti, Juliane, additional, Fisher, Paul R., additional, García, Adolfo M., additional, Garrido-Gil, Pablo, additional, Giagkou, Nikolaos, additional, Goldberg, Joshua A., additional, Greggio, Elisa, additional, Guzzi, Giusy, additional, Hang, Liting, additional, Heilman, Kenneth M., additional, Hosamani, Dr. Ravikumar, additional, Hu, Xiaoping P., additional, Huddleston, Daniel E., additional, Ibáñez, Agustín, additional, Ilkiw, Jessica L., additional, Inoue, Kiyoharu, additional, Ip, Chi Wang, additional, Jimenez-Del-Rio, Marlene, additional, Kaczyńska, Katarzyna, additional, Kenna, Jade, additional, Kim, Eung Yeop, additional, Kochanski, Ryan B., additional, Kohler, Verena, additional, Komuro, Jéssica Emy, additional, Koprich, James B., additional, Koros, Chistos, additional, Kunugi, Hiroshi, additional, Kuter, Katarzyna, additional, Labandeira-Garcia, Jose Luis, additional, Labandeira, Carmen M., additional, Langley, Jason, additional, Lauretti, Elisabetta, additional, Lavano, Angelo, additional, Lee, Jongho, additional, Lim, Kah-Leong, additional, Lima, Marcelo M.S., additional, Magalhães, João Duarte, additional, Mitrofanis, John, additional, Møller, Simon G., additional, Mroczek, Katelyn H., additional, Musacchio, Thomas, additional, Musco, Vanessa J., additional, Musgrove, Ruth E., additional, Noseda, Ana Carolina D., additional, O'Hashi, Kazunori, additional, Olchik, Maira Rozenfeld, additional, Oliveira-Giacomelli, Ágatha, additional, Orozco-Arroyave, Juan Rafael, additional, Padovani, Marina, additional, Papini, Silvia Justina, additional, Patel, Vinood B., additional, Patil, Ketan S., additional, Pedrosa, Maria A., additional, Praticò, Domenico, additional, Preedy, Victor R., additional, Puginier, Emilie, additional, Puig-Butillé, Joan Anton, additional, Puig, Susana, additional, Rajendram, Rajkumar, additional, Richardson, Jason R., additional, Rodrigues, Lais S., additional, Rodriguez-Perez, Ana I., additional, Rosen, Benjamin, additional, Sani, Sepehr, additional, Santos, Daniel, additional, Schelp, Arthur Oscar, additional, Schuff, Norbert, additional, Sedeño, Lucas, additional, Silva, Diana F., additional, Simitsi, Athina-Maria, additional, Sohya, Kazuhiro, additional, Stamelou, Maria, additional, Stefanis, Leonidas, additional, Sung, Young Hee, additional, Targa, Adriano D.S., additional, Tell-Marti, Gemma, additional, Toft, Mathias, additional, Tomic, Svetlana, additional, Torre, Attilio Della, additional, Torre, Domenico La, additional, Tosun, Duygu, additional, Ulrich, Henning, additional, Varanita, Tatiana, additional, Velez-Pardo, Carlos, additional, Volta, Mattia, additional, Warabi, Tateo, additional, Wenning, Leslie, additional, Wu, I-Wei, additional, Xiong, Yulan, additional, Yanagisawa, Nobuo, additional, Yu, Jianzhong, additional, Zhang, Yu, additional, and Zhou, Fu-Ming, additional

Published
2020
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39. Mitochondrial haplogroups and cognitive progression in Parkinson's disease

Author

Liu, Ganqiang, Ni, Chunming, Zhan, Jiamin, Li, Weimin, Luo, Junfeng, Liao, Zhixiang, Locascio, Joseph J, Xian, Wenbiao, Chen, Ling, Pei, Zhong, Corvol, Jean-Christophe, Maple-Grødem, Jodi, Campbell, Meghan C, Elbaz, Alexis, Lesage, Suzanne, Brice, Alexis, Hung, Albert Y, Schwarzschild, Michael A, Hayes, Michael T, Wills, Anne-Marie, Ravina, Bernard, Shoulson, Ira, Taba, Pille, Kõks, Sulev, Beach, Thomas G, Cormier-Dequaire, Florence, Alves, Guido, Tysnes, Ole-Bjørn, Perlmutter, Joel S, Heutink, Peter, Van Hilten, Jacobus J, Barker, Roger A, Williams-Gray, Caroline H, Scherzer, Clemens R, International Genetics Of Parkinson Disease Progression (IGPP) Consortium, Liu, Ganqiang [0000-0002-1921-9542], Pei, Zhong [0000-0002-8425-2867], Elbaz, Alexis [0000-0001-9724-5490], Apollo - University of Cambridge Repository, Liu, Ganqiang, Valentino, Rebecca R, Peng, Jiajie, Liao, Zhixiang, Locascio, Joseph J, Corvol, Jean-Christophe, Dong, Xianjun, Maple-Grødem, Jodi, Campbell, Meghan C, Elbaz, Alexis, Lesage, Suzanne, Brice, Alexis, Mangone, Graziella, Growdon, John H, Hung, Albert Y, Schwarzchild, Michael A, Hayes, Michael T, Wills, Anne-Marie, Herrington, Todd M, Ravian, Bernard, Shoulson, Ira, Taba, Pille, Kõks, Sulev, Beach, Thomas G, Cormier-Dequaire, Florence, Alves, Guido, Tysnes, Ole-Bjørn, Perlmutter, Joel S, Heutink, Peter, van Hilten, Jacobus J, Kasten, Meike, Mollenhauer, Brit, Trenkwalder, Claudia, Klein, Christine, Barker, Roger A, Williams-Gray, Caroline H, Marinus, Johan, and Scherzer, Clemens R

Subjects
mitochondrial haplogroups, Parkinson's disease, cognitive progression, Parkinson Disease, genetics [DNA, Mitochondrial], DNA, Mitochondrial, Mitochondria, Cognition, Haplotypes, genetics [Parkinson Disease], Report, Parkinson’s disease, Disease Progression, Humans, Neurology (clinical), ddc:610, epidemiology [Parkinson Disease], genetics [Mitochondria]
Abstract

Liu et al. report that specific mitochondrial haplogroups are associated with the progression of cognitive decline in patients with Parkinson's disease, but not with the progression of motor impairment. Mitochondrial haplotypes may thus be useful for stratifying patients according to their risk of cognitive decline.Mitochondria are a culprit in the onset of Parkinson's disease, but their role during disease progression is unclear. Here we used Cox proportional hazards models to exam the effect of variation in the mitochondrial genome on longitudinal cognitive and motor progression over time in 4064 patients with Parkinson's disease. Mitochondrial macro-haplogroup was associated with reduced risk of cognitive disease progression in the discovery and replication population. In the combined analysis, patients with the super macro-haplogroup J, T, U-# had a 41% lower risk of cognitive progression with P = 2.42 x 10(-6) compared to those with macro-haplogroup H. Exploratory analysis indicated that the common mitochondrial DNA variant, m.2706A>G, was associated with slower cognitive decline with a hazard ratio of 0.68 (95% confidence interval 0.56-0.81) and P = 2.46 x 10(-5). Mitochondrial haplogroups were not appreciably linked to motor progression. This initial genetic survival study of the mitochondrial genome suggests that mitochondrial haplogroups may be associated with the pace of cognitive progression in Parkinson's disease over time.

Published
2023

40. Genetic risk of Parkinson disease and progression: An analysis of 13 longitudinal cohorts

Author

Iwaki, Hirotaka, Blauwendraat, Cornelis, Leonard, Hampton L., Liu, Ganqiang, Maple-Grødem, Jodi, Corvol, Jean-Christophe, Pihlstrøm, Lasse, van Nimwegen, Marlies, Hutten, Samantha J., Nguyen, Khanh-Dung H., Rick, Jacqueline, Eberly, Shirley, Faghri, Faraz, Auinger, Peggy, Scott, Kirsten M., Wijeyekoon, Ruwani, Van Deerlin, Vivianna M., Hernandez, Dena G., Day-Williams, Aaron G., Brice, Alexis, Alves, Guido, Noyce, Alastair J., Tysnes, Ole-Bjørn, Evans, Jonathan R., Breen, David P., Estrada, Karol, Wegel, Claire E., Danjou, Fabrice, Simon, David K., Ravina, Bernard, Toft, Mathias, Heutink, Peter, Bloem, Bastiaan R., Weintraub, Daniel, Barker, Roger A., Williams-Gray, Caroline H., van de Warrenburg, Bart P., Van Hilten, Jacobus J., Scherzer, Clemens R., Singleton, Andrew B., and Nalls, Mike A.

Published
2019
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41. Cognitive and motor decline in Dementia with Lewy bodies and Parkinson's Disease Dementia

Author

Gonzalez, Maria Camila, primary, Tovar‐Rios, Diego Alejandro, additional, Alves, Guido, additional, Dalen, Ingvild, additional, Williams‐Gray, Caroline H., additional, Camacho, Marta, additional, Forsgren, Lars, additional, Bäckström, David, additional, Lawson, Rachael A., additional, Macleod, Angus D., additional, Counsell, Carl E., additional, Paquet, Claire, additional, De Lena, Carlo, additional, D'Antonio, Fabrizia, additional, Pilotto, Andrea, additional, Padovani, Alessandro, additional, Blanc, Frédéric, additional, Falup‐Pecurariu, Cristian, additional, Lewis, Simon J.G., additional, Rejdak, Konrad, additional, Papuc, Ewa, additional, Hort, Jakub, additional, Nedelska, Zuzana, additional, O'Brien, John, additional, Bonanni, Laura, additional, Marquié, Marta, additional, Boada, Mercè, additional, Pytel, Vanesa, additional, Abdelnour, Carla, additional, Alcolea, Daniel, additional, Beyer, Katrin, additional, Tysnes, Ole‐Bjørn, additional, Aarsland, Dag, additional, and Maple‐Grødem, Jodi, additional

Published
2023
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43. Cognitive and motor decline in dementia with lewy bodies and Parkinson's disease dementia

Author

Gonzalez, Maria Camila, Tovar-Rios, Diego Alejandro, Alves, Guido, Dalen, Ingvild, Williams-Gray, Caroline H., Camacho, Marta, Forsgren, Lars, Bäckström, David C, Lawson, Rachael A., Macleod, Angus D., Counsell, Carl E., Paquet, Claire, DeLena, Carlo, D'Antonio, Fabrizia, Pilotto, Andrea, Padovani, Alessandro, Blanc, Frédéric, Falup-Pecurariu, Cristian, Lewis, Simon J.G., Rejdak, Konrad, Papuc, Ewa, Hort, Jakub, Nedelska, Zuzana, O'Brien, John, Bonanni, Laura, Marquié, Marta, Boada, Mercè, Pytel, Vanesa, Abdelnour, Carla, Alcolea, Daniel, Beyer, Katrin, Tysnes, Ole-Bjørn, Aarsland, Dag, Maple-Grødem, Jodi, Gonzalez, Maria Camila, Tovar-Rios, Diego Alejandro, Alves, Guido, Dalen, Ingvild, Williams-Gray, Caroline H., Camacho, Marta, Forsgren, Lars, Bäckström, David C, Lawson, Rachael A., Macleod, Angus D., Counsell, Carl E., Paquet, Claire, DeLena, Carlo, D'Antonio, Fabrizia, Pilotto, Andrea, Padovani, Alessandro, Blanc, Frédéric, Falup-Pecurariu, Cristian, Lewis, Simon J.G., Rejdak, Konrad, Papuc, Ewa, Hort, Jakub, Nedelska, Zuzana, O'Brien, John, Bonanni, Laura, Marquié, Marta, Boada, Mercè, Pytel, Vanesa, Abdelnour, Carla, Alcolea, Daniel, Beyer, Katrin, Tysnes, Ole-Bjørn, Aarsland, Dag, and Maple-Grødem, Jodi

Abstract

Background: There is a need to better understand the rate of cognitive and motor decline of Dementia with Lewy bodies (DLB) and Parkinson's disease Dementia (PDD). Objectives: To compare the rate of cognitive and motor decline in patients with DLB and PDD from the E-DLB Consortium and the Parkinson's Incidence Cohorts Collaboration (PICC) Cohorts. Methods: The annual change in MMSE and MDS-UPDRS part III was estimated using linear mixed regression models in patients with at least one follow-up (DLB n = 837 and PDD n = 157). Results: When adjusting for confounders, we found no difference in the annual change in MMSE between DLB and PDD (−1.8 [95% CI −2.3, −1.3] vs. −1.9 [95% CI −2.6, −1.2] [P = 0.74]). MDS-UPDRS part III showed nearly identical annual changes (DLB 4.8 [95% CI 2.1, 7.5]) (PDD 4.8 [95% CI 2.7, 6.9], [P = 0.98]). Conclusions: DLB and PDD showed similar rates of cognitive and motor decline. This is relevant for future clinical trial designs.

Published
2023
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