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1. The Parkinson's progression markers initiative (PPMI) - establishing a PD biomarker cohort.

Author

Marek, Kenneth, Chowdhury, Sohini, Siderowf, Andrew, Lasch, Shirley, Coffey, Christopher S, Caspell-Garcia, Chelsea, Simuni, Tanya, Jennings, Danna, Tanner, Caroline M, Trojanowski, John Q, Shaw, Leslie M, Seibyl, John, Schuff, Norbert, Singleton, Andrew, Kieburtz, Karl, Toga, Arthur W, Mollenhauer, Brit, Galasko, Doug, Chahine, Lana M, Weintraub, Daniel, Foroud, Tatiana, Tosun-Turgut, Duygu, Poston, Kathleen, Arnedo, Vanessa, Frasier, Mark, Sherer, Todd, and Parkinson's Progression Markers Initiative

Subjects
Parkinson's Progression Markers Initiative, Neurosciences, Aging, Biomedical Imaging, Clinical Trials and Supportive Activities, Parkinson's Disease, Brain Disorders, Neurodegenerative, Clinical Research, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, Neurological, Clinical Sciences
Abstract

ObjectiveThe Parkinson's Progression Markers Initiative (PPMI) is an observational, international study designed to establish biomarker-defined cohorts and identify clinical, imaging, genetic, and biospecimen Parkinson's disease (PD) progression markers to accelerate disease-modifying therapeutic trials.MethodsA total of 423 untreated PD, 196 Healthy Control (HC) and 64 SWEDD (scans without evidence of dopaminergic deficit) subjects were enrolled at 24 sites. To enroll PD subjects as early as possible following diagnosis, subjects were eligible with only asymmetric bradykinesia or tremor plus a dopamine transporter (DAT) binding deficit on SPECT imaging. Acquisition of data was standardized as detailed at www.ppmi-info.org.ResultsApproximately 9% of enrolled subjects had a single PD sign at baseline. DAT imaging excluded 16% of potential PD subjects with SWEDD. The total MDS-UPDRS for PD was 32.4 compared to 4.6 for HC and 28.2 for SWEDD. On average, PD subjects demonstrated 45% and 68% reduction in mean striatal and contralateral putamen Specific Binding Ratios (SBR), respectively. Cerebrospinal fluid (CSF) was acquired from >97% of all subjects. CSF (PD/HC/SWEDD pg/mL) α-synuclein (1845/2204/2141) was reduced in PD vs HC or SWEDD (P

Published
2018

2. Longitudinal Change of Clinical and Biological Measures in Early Parkinson's Disease: Parkinson's Progression Markers Initiative Cohort.

Author

Simuni, Tanya, Siderowf, Andrew, Lasch, Shirley, Coffey, Chris S, Caspell-Garcia, Chelsea, Jennings, Danna, Tanner, Caroline M, Trojanowski, John Q, Shaw, Leslie M, Seibyl, John, Schuff, Norbert, Singleton, Andrew, Kieburtz, Karl, Toga, Arthur W, Mollenhauer, Brit, Galasko, Doug, Chahine, Lana M, Weintraub, Daniel, Foroud, Tatiana, Tosun, Duygu, Poston, Kathleen, Arnedo, Vanessa, Frasier, Mark, Sherer, Todd, Chowdhury, Sohini, Marek, Kenneth, and Parkinson's Progression Marker Initiative*

Subjects
Parkinson's Progression Marker Initiative*, Corpus Striatum, Humans, Parkinson Disease, Disease Progression, Nortropanes, Peptide Fragments, tau Proteins, Cohort Studies, Age Factors, Aged, Middle Aged, Female, Male, Dopamine Plasma Membrane Transport Proteins, Amyloid beta-Peptides, Parkinson's disease, disease subtypes, gait disorder predominant, postural instability, tremor dominant, Neurodegenerative, Clinical Research, Parkinson's Disease, Brain Disorders, Aging, Neurosciences, Neurological, Neurology & Neurosurgery, Clinical Sciences, Human Movement and Sports Sciences
Abstract

OBJECTIVE:The objective of this study was to assess longitudinal change in clinical and dopamine transporter imaging outcomes in early, untreated PD. METHODS:We describe 5-year longitudinal change of the MDS-UPDRS and other clinical measures using results from the Parkinson's Progression Markers Initiative, a longitudinal cohort study of early Parkinson's disease (PD) participants untreated at baseline. We also provide data on the longitudinal change in dopamine transporter 123-I Ioflupane striatal binding and correlation between the 2 measures. RESULTS:A total of 423 PD participants were recruited, and 358 remain in the study at year 5. Baseline MDS-UPDRS total score was 32.4 (standard deviation 13.1), and the average annual change (assessed medications OFF for the treated participants) was 7.45 (11.6), 3.11 (11.7), 4(11.9), 4.7 (11.1), and 1.74(11.9) for years 1, 2, 3, 4, and 5, respectively (P

Published
2018

3. Baseline prevalence and longitudinal evolution of non-motor symptoms in early Parkinson’s disease: the PPMI cohort

Author

Simuni, Tanya, Caspell-Garcia, Chelsea, Coffey, Christopher S, Weintraub, Daniel, Mollenhauer, Brit, Lasch, Shirley, Tanner, Caroline M, Jennings, Danna, Kieburtz, Karl, Chahine, Lana M, and Marek, Kenneth

Subjects
Neurodegenerative, Brain Disorders, Clinical Research, Prevention, Aging, Parkinson's Disease, Neurosciences, Aetiology, 2.1 Biological and endogenous factors, Neurological, Age Factors, Amyloid beta-Peptides, Biomarkers, Disease Progression, Early Diagnosis, Female, Humans, Longitudinal Studies, Male, Middle Aged, Parkinson Disease, Prevalence, Prospective Studies, Severity of Illness Index, Sex Factors, biomarkers, non-motor symptoms, parkinson’s disease, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery
Abstract

ObjectiveTo examine the baseline prevalence and longitudinal evolution in non-motor symptoms (NMS) in a prospective cohort of, at baseline, patients with de novo Parkinson's disease (PD) compared with healthy controls (HC).MethodsParkinson's Progression Markers Initiative (PPMI) is a longitudinal, ongoing, controlled study of de novo PD participants and HC. NMS were rated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I score and other validated NMS scales at baseline and after 2 years. Biological variables included cerebrospinal fluid (CSF) markers and dopamine transporter imaging.Results423 PD subjects and 196 HC were enrolled and followed for 2 years. MDS-UPDRS Part I total mean (SD) scores increased from baseline 5.6 (4.1) to 7.7 (5.0) at year 2 in PD subjects (p

Published
2018

4. Cognition among individuals along a spectrum of increased risk for Parkinson's disease.

Author

Chahine, Lana M, Urbe, Liz, Caspell-Garcia, Chelsea, Aarsland, Dag, Alcalay, Roy, Barone, Paolo, Burn, David, Espay, Alberto J, Hamilton, Jamie L, Hawkins, Keith A, Lasch, Shirley, Leverenz, James B, Litvan, Irene, Richard, Irene, Siderowf, Andrew, Coffey, Christopher S, Simuni, Tanya, Weintraub, Daniel, and Parkinson’s Progression Markers Initiative

Subjects
Parkinson’s Progression Markers Initiative, Humans, Parkinson Disease, Disease Susceptibility, Risk Assessment, Risk Factors, Cohort Studies, Cognition, Neuropsychological Tests, Mutation, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Biomarkers, General Science & Technology
Abstract

INTRODUCTION:Several characteristics associated with increased risk for Parkinson's disease (PD) have been identified, including specific genotypes and various non-motor symptoms. Characterizing non-motor features, such as cognitive abilities, among individuals considered at-risk for PD is essential to improving prediction of future neurodegeneration. METHODS:Participants belonging to the following cohorts of the Parkinson Progression Markers Initiative (PPMI) study were included: de novo PD with dopamine transporter binding deficit (n = 423), idiopathic REM sleep behavior disorder (RBD, n = 39), hyposmia (n = 26) and non-PD mutation carrier (NMC; Leucine-rich repeat kinase 2 (LRRK2) G2019S (n = 88) and glucocerebrosidase (GBA) gene (n = 38) mutations)). Inclusion criteria enriched the RBD and hyposmia cohorts, but not the NMC cohort, with individuals with dopamine transporter binding deficit. Baseline neuropsychological performance was compared, and analyses were adjusted for age, sex, education, and depression. RESULTS:The RBD cohort performed significantly worse than the hyposmia and NMC cohorts on Symbol Digit Modality Test (mean (SD) 32.4 (9.16) vs. 41.8 (9.98), p = 0.002 and vs. 45.2 (10.9), p

Published
2018

5. Multiple modality biomarker prediction of cognitive impairment in prospectively followed de novo Parkinson disease

Author

Caspell-Garcia, Chelsea, Simuni, Tanya, Tosun-Turgut, Duygu, Wu, I-Wei, Zhang, Yu, Nalls, Mike, Singleton, Andrew, Shaw, Leslie A, Kang, Ju-Hee, Trojanowski, John Q, Siderowf, Andrew, Coffey, Christopher, Lasch, Shirley, Aarsland, Dag, Burn, David, Chahine, Lana M, Espay, Alberto J, Foster, Eric D, Hawkins, Keith A, Litvan, Irene, Richard, Irene, and Weintraub, Daniel

Subjects
Dementia, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurosciences, Biomedical Imaging, Acquired Cognitive Impairment, Neurodegenerative, Parkinson's Disease, Alzheimer's Disease, Clinical Research, Brain Disorders, Prevention, Genetics, Aging, Aetiology, 2.1 Biological and endogenous factors, Neurological, Adult, Aged, Aged, 80 and over, Amyloid beta-Peptides, Biomarkers, Brain-Derived Neurotrophic Factor, Catechol O-Methyltransferase, Cognitive Dysfunction, Diffusion Tensor Imaging, Dopamine Plasma Membrane Transport Proteins, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Parkinson Disease, Polymorphism, Single Nucleotide, Tomography, Emission-Computed, Single-Photon, tau Proteins, Parkinson’s Progression Markers Initiative, General Science & Technology
Abstract

ObjectivesTo assess the neurobiological substrate of initial cognitive decline in Parkinson's disease (PD) to inform patient management, clinical trial design, and development of treatments.MethodsWe longitudinally assessed, up to 3 years, 423 newly diagnosed patients with idiopathic PD, untreated at baseline, from 33 international movement disorder centers. Study outcomes were four determinations of cognitive impairment or decline, and biomarker predictors were baseline dopamine transporter (DAT) single photon emission computed tomography (SPECT) scan, structural magnetic resonance imaging (MRI; volume and thickness), diffusion tensor imaging (mean diffusivity and fractional anisotropy), cerebrospinal fluid (CSF; amyloid beta [Aβ], tau and alpha synuclein), and 11 single nucleotide polymorphisms (SNPs) previously associated with PD cognition. Additionally, longitudinal structural MRI and DAT scan data were included. Univariate analyses were run initially, with false discovery rate = 0.2, to select biomarker variables for inclusion in multivariable longitudinal mixed-effect models.ResultsBy year 3, cognitive impairment was diagnosed in 15-38% participants depending on the criteria applied. Biomarkers, some longitudinal, predicting cognitive impairment in multivariable models were: (1) dopamine deficiency (decreased caudate and putamen DAT availability); (2) diffuse, cortical decreased brain volume or thickness (frontal, temporal, parietal, and occipital lobe regions); (3) co-morbid Alzheimer's disease Aβ amyloid pathology (lower CSF Aβ 1-42); and (4) genes (COMT val/val and BDNF val/val genotypes).ConclusionsCognitive impairment in PD increases in frequency 50-200% in the first several years of disease, and is independently predicted by biomarker changes related to nigrostriatal or cortical dopaminergic deficits, global atrophy due to possible widespread effects of neurodegenerative disease, co-morbid Alzheimer's disease plaque pathology, and genetic factors.

Published
2017

6. Predictors of time to initiation of symptomatic therapy in early Parkinson's disease

Author

Simuni, Tanya, Long, Jeffrey D, Caspell‐Garcia, Chelsea, Coffey, Christopher S, Lasch, Shirley, Tanner, Caroline M, Jennings, Danna, Kieburtz, Karl D, Marek, Kenneth, and Investigators, the PPMI

Subjects
Clinical and Health Psychology, Biomedical and Clinical Sciences, Neurosciences, Psychology, Neurodegenerative, Aging, Prevention, Parkinson's Disease, Brain Disorders, Clinical Research, Neurological, PPMI Investigators, Biomarkers, Parkinson's disease, symptomatic therapy, Clinical Sciences, Clinical and health psychology
Abstract

ObjectiveTo determine clinical and biological variables that predict time to initiation of symptomatic therapy in de novo Parkinson's disease patients.MethodsParkinson's Progression Markers Initiative is a longitudinal case-control study of de novo, untreated Parkinson's disease participants at enrolment. Participants contribute a wide range of motor and non-motor measures, including biofluids and imaging biomarkers. The machine learning method of random survival forests was used to examine the ability of baseline variables to predict time to initiation of symptomatic therapy since study enrollment (baseline).ResultsThere were 423 PD participants enrolled in PPMI and 33 initial baseline variables. Cross-validation results showed that the three-predictor subset of disease duration (time from diagnosis to enrollment), the modified Schwab and England activities of daily living scale, and the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) total score modestly predicted time to initiation of symptomatic therapy (C = 0.70, pseudo-R (2) = 0.13). Prediction using the three variables was similar to using the entire set of 33. None of the biological variables increased accuracy of the prediction. A prognostic index for time to initiation of symptomatic therapy was created using the linear and nonlinear effects of the three top variables based on a post hoc Cox model.InterpretationOur findings using a novel machine learning method support previously reported clinical variables that predict time to initiation of symptomatic therapy. However, the inclusion of biological variables did not increase prediction accuracy. Our prognostic index constructed, based on the group-level survival curve can provide an indication of the risk of initiation of ST for PD patients based on functions of the three top predictors.

Published
2016

7. Cognitive performance and neuropsychiatric symptoms in early, untreated Parkinson's disease.

Author

Weintraub, Daniel, Simuni, Tanya, Caspell-Garcia, Chelsea, Coffey, Christopher, Lasch, Shirley, Siderowf, Andrew, Aarsland, Dag, Barone, Paolo, Burn, David, Chahine, Lama M, Eberling, Jamie, Espay, Alberto J, Foster, Eric D, Leverenz, James B, Litvan, Irene, Richard, Irene, Troyer, Matthew D, Hawkins, Keith A, and Parkinson's Progression Markers Initiative

Subjects
Parkinson's Progression Markers Initiative, Humans, Parkinson Disease, Severity of Illness Index, Prevalence, Depression, Anxiety, Mental Disorders, Cognition Disorders, Psychotic Disorders, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Apathy, Biomarkers, Disruptive, Impulse Control, and Conduct Disorders, Cognitive Dysfunction, Parkinson's disease, anxiety, apathy, cognition, depression, impulse control disorder, psychosis, Clinical Research, Parkinson's Disease, Aging, Neurodegenerative, Neurosciences, Serious Mental Illness, Brain Disorders, Mental Health, Behavioral and Social Science, 2.1 Biological and endogenous factors, Aetiology, Mental health, Neurological, Clinical Sciences, Human Movement and Sports Sciences, Neurology & Neurosurgery
Abstract

UnlabelledThis study was undertaken to determine the prevalence and correlates of cognitive impairment (CI) and neuropsychiatric symptoms (NPS) in early, untreated patients with Parkinson's disease (PD).BackgroundBoth CI and NPS are common in PD and impact disease course and quality of life. However, limited knowledge is available about cognitive abilities and NPS.MethodsParkinson's Progression Markers Initiative (PPMI) is a multi-site study of early, untreated PD patients and healthy controls (HCs), the latter with normal cognition. At baseline, participants were assessed with a neuropsychological battery and for symptoms of depression, anxiety, impulse control disorders (ICDs), psychosis, and apathy.ResultsBaseline data of 423 PD patients and 196 HCs yielded no between-group differences in demographic characteristics. Twenty-two percent of PD patients met the PD-recommended screening cutoff for CI on the Montral Cognitive Assessment (MoCA), but only 9% met detailed neuropsychological testing criteria for mild cognitive impairment (MCI)-level impairment. The PD patients were more depressed than HCs (P

Published
2015

8. Association of Cerebrospinal Fluid β-Amyloid 1-42, T-tau, P-tau181, and α-Synuclein Levels With Clinical Features of Drug-Naive Patients With Early Parkinson Disease

Author

Kang, Ju-Hee, Irwin, David J, Chen-Plotkin, Alice S, Siderowf, Andrew, Caspell, Chelsea, Coffey, Christopher S, Waligórska, Teresa, Taylor, Peggy, Pan, Sarah, Frasier, Mark, Marek, Kenneth, Kieburtz, Karl, Jennings, Danna, Simuni, Tanya, Tanner, Caroline M, Singleton, Andrew, Toga, Arthur W, Chowdhury, Sohini, Mollenhauer, Brit, Trojanowski, John Q, Shaw, Leslie M, Lasch, Shirley, Flagg, Emily, Poewe, Werner, Sherer, Todd, Meunier, Claire, Rudolph, Alice, Casaceli, Cindy, Seibyl, John, Mendick, Susan, Schuff, Norbert, Uribe, Liz, Yankey, Jon, Crawford, Karen, Scutti, Alison, Casalin, Paola, Malferrari, Giulia, Hawkins, Keith, Russell, David, Leary, Laura, Factor, Stewart, Sommerfeld, Barbara, Hogarth, Penelope, Pighetti, Emily, Williams, Karen, Standaert, David, Guthrie, Stephanie, Hauser, Robert, Jankovic, Joseph, Hunter, Christine, Stern, Matthew, Darin, Abigail, Leverenz, Jim, Baca, Marne, Frank, Sam, Thomas, Cathi-Ann, Richard, Irene, Deeley, Cheryl, Rees, Linda, Sprenger, Fabienne, Oertel, Wolfgang, Willeke, Diana, Shill, Holly, Fernandez, Hubert, Mule, Jennifer, Berg, Daniela, Gauss, Katharina, Galasko, Douglas, Fontaine, Deborah, Mari, Zoltan, McCoy, Arita, Brooks, David, Shah, Bina, Barone, Paolo, Isaacson, Stuart, James, Angela, Espay, Alberto, Espay, Kristy, Rowe, Dominic, and Ranola, Madelaine

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Neurosciences, Aging, Neurodegenerative, Brain Disorders, Dementia, Acquired Cognitive Impairment, Parkinson's Disease, Clinical Research, 2.1 Biological and endogenous factors, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, 4.1 Discovery and preclinical testing of markers and technologies, Aetiology, Neurological, Amyloid beta-Peptides, Case-Control Studies, Cohort Studies, Female, Humans, Male, Memory, Middle Aged, Movement, Neuropsychological Tests, Parkinson Disease, Peptide Fragments, Phosphorylation, Regression Analysis, Severity of Illness Index, Statistics as Topic, Threonine, Verbal Learning, alpha-Synuclein, tau Proteins, Parkinson's Progression Markers Initiative
Abstract

ImportanceWe observed a significant correlation between cerebrospinal fluid (CSF) levels of tau proteins and α-synuclein, but not β-amyloid 1-42 (Aβ1-42), and lower concentration of CSF biomarkers, as compared with healthy controls, in a cohort of entirely untreated patients with Parkinson disease (PD) at the earliest stage of the disease studied so far.ObjectiveTo evaluate the baseline characteristics and relationship to clinical features of CSF biomarkers (Aβ1-42, total tau [T-tau], tau phosphorylated at threonine 181 [P-tau181], and α-synuclein) in drug-naive patients with early PD and demographically matched healthy controls enrolled in the Parkinson's Progression Markers Initiative (PPMI) study.Design, setting, and participantsCross-sectional study of the initial 102 research volunteers (63 patients with PD and 39 healthy controls) of the PPMI cohort.Main outcomes and measuresThe CSF biomarkers were measured by INNO-BIA AlzBio3 immunoassay (Aβ1-42, T-tau, and P-tau181; Innogenetics Inc) or by enzyme-linked immunosorbent assay (α-synuclein). Clinical features including diagnosis, demographic characteristics, motor, neuropsychiatric, and cognitive assessments, and DaTscan were systematically assessed according to the PPMI study protocol.ResultsSlightly, but significantly, lower levels of Aβ1-42, T-tau, P-tau181, α-synuclein, and T-tau/Aβ1-42 were seen in subjects with PD compared with healthy controls but with a marked overlap between groups. Using multivariate regression analysis, we found that lower Aβ1-42 and P-tau181 levels were associated with PD diagnosis and that decreased CSF T-tau and α-synuclein were associated with increased motor severity. Notably, when we classified patients with PD by their motor phenotypes, lower CSF Aβ1-42 and P-tau181 concentrations were associated with the postural instability-gait disturbance-dominant phenotype but not with the tremor-dominant or intermediate phenotype. Finally, we found a significant correlation of the levels of α-synuclein with the levels of T-tau and P-tau181.Conclusions and relevanceIn this first report of CSF biomarkers in PPMI study subjects,we found that measures of CSF Aβ1-42, T-tau, P-tau181, and α-synuclein have prognostic and diagnostic potential in early-stage PD. Further investigations using the entire PPMI cohort will test the predictive performance of CSF biomarkers for PD progression

Published
2013

11. The genetic architecture of the human cerebral cortex

Author

Grasby, Katrina L, Jahanshad, Neda, Shatokhina, Natalia, Mirza-Schreiber, Nazanin, Moreira, Jose C V, Mühleisen, Thomas W, Müller-Myhsok, Bertram, Najt, Pablo, Nakahara, Soichiro, Nho, Kwangsik, Olde Loohuis, Loes M, Orfanos, Dimitri Papadopoulos, Pearson, John F, Zsembik, Leo C P, Pitcher, Toni L, Pütz, Benno, Quidé, Yann, Ragothaman, Anjanibhargavi, Rashid, Faisal M, Reay, William R, Redlich, Ronny, Reinbold, Céline S, Repple, Jonathan, Richard, Geneviève, Thomopoulos, Sophia I, Riedel, Brandalyn C, Risacher, Shannon L, Rocha, Cristiane S, Mota, Nina Roth, Salminen, Lauren, Saremi, Arvin, Saykin, Andrew J, Schlag, Fenja, Schmaal, Lianne, Schofield, Peter R, Zhu, Alyssa H, Secolin, Rodrigo, Shapland, Chin Yang, Shen, Li, Shin, Jean, Shumskaya, Elena, Sønderby, Ida E, Sprooten, Emma, Tansey, Katherine E, Teumer, Alexander, Thalamuthu, Anbupalam, Strike, Lachlan T, Tordesillas-Gutiérrez, Diana, Turner, Jessica A, Uhlmann, Anne, Vallerga, Costanza Ludovica, van der Meer, Dennis, van Donkelaar, Marjolein M J, van Eijk, Liza, van Erp, Theo G M, van Haren, Neeltje E M, van Rooij, Daan, Agartz, Ingrid, van Tol, Marie-José, Veldink, Jan H, Verhoef, Ellen, Walton, Esther, Wang, Mingyuan, Wang, Yunpeng, Wardlaw, Joanna M, Wen, Wei, Westlye, Lars T, Whelan, Christopher D, Alhusaini, Saud, Witt, Stephanie H, Wittfeld, Katharina, Wolf, Christiane, Wolfers, Thomas, Wu, Jing Qin, Yasuda, Clarissa L, Zaremba, Dario, Zhang, Zuo, Zwiers, Marcel P, Artiges, Eric, Almeida, Marcio A A, Assareh, Amelia A, Ayesa-Arriola, Rosa, Belger, Aysenil, Brandt, Christine L, Brown, Gregory G, Cichon, Sven, Curran, Joanne E, Davies, Gareth E, Degenhardt, Franziska, Dennis, Michelle F, Alnæs, Dag, Dietsche, Bruno, Djurovic, Srdjan, Doherty, Colin P, Espiritu, Ryan, Garijo, Daniel, Gil, Yolanda, Gowland, Penny A, Green, Robert C, Häusler, Alexander N, Heindel, Walter, Amlien, Inge K, Ho, Beng-Choon, Hoffmann, Wolfgang U, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Jack, Clifford R, Jang, MiHyun, Jansen, Andreas, Kimbrel, Nathan A, Kolskår, Knut, Painter, Jodie N, Andersson, Micael, Koops, Sanne, Krug, Axel, Lim, Kelvin O, Luykx, Jurjen J, Mathalon, Daniel H, Mather, Karen A, Mattay, Venkata S, Matthews, Sarah, Mayoral Van Son, Jaqueline, McEwen, Sarah C, Ard, Tyler, Melle, Ingrid, Morris, Derek W, Mueller, Bryon A, Nauck, Matthias, Nordvik, Jan E, Nöthen, Markus M, O'Leary, Daniel S, Opel, Nils, Martinot, Marie-Laure Paillère, Pike, G Bruce, Armstrong, Nicola J, Preda, Adrian, Quinlan, Erin B, Rasser, Paul E, Ratnakar, Varun, Reppermund, Simone, Steen, Vidar M, Tooney, Paul A, Torres, Fábio R, Veltman, Dick J, Voyvodic, James T, Ashley-Koch, Allison, Whelan, Robert, White, Tonya, Yamamori, Hidenaga, Adams, Hieab H H, Bis, Joshua C, Debette, Stephanie, Decarli, Charles, Fornage, Myriam, Gudnason, Vilmundur, Hofer, Edith, Atkins, Joshua R, Ikram, M Arfan, Launer, Lenore, Longstreth, W. T., Lopez, Oscar L, Mazoyer, Bernard, Mosley, Thomas H, Roshchupkin, Gennady V, Satizabal, Claudia L, Schmidt, Reinhold, Seshadri, Sudha, Bernard, Manon, Yang, Qiong, Initiative, Alzheimer’s Disease Neuroimaging, Consortium, CHARGE, Consortium, EPIGEN, Consortium, IMAGEN, Consortium, SYS, Initiative, Parkinson’s Progression Markers, Alvim, Marina K M, Ames, David, Anderson, Tim J, Brouwer, Rachel M, Andreassen, Ole A, Arias-Vasquez, Alejandro, Bastin, Mark E, Baune, Bernhard T, Beckham, Jean C, Blangero, John, Boomsma, Dorret I, Brodaty, Henry, Brunner, Han G, Buckner, Randy L, Buimer, Elizabeth E L, Buitelaar, Jan K, Bustillo, Juan R, Cahn, Wiepke, Cairns, Murray J, Calhoun, Vince, Carr, Vaughan J, Caseras, Xavier, Caspers, Svenja, Cavalleri, Gianpiero L, Cendes, Fernando, Bülow, Robin, Corvin, Aiden, Crespo-Facorro, Benedicto, Dalrymple-Alford, John C, Dannlowski, Udo, de Geus, Eco J C, Deary, Ian J, Delanty, Norman, Depondt, Chantal, Desrivières, Sylvane, Donohoe, Gary, Bürger, Christian, Espeseth, Thomas, Fernández, Guillén, Fisher, Simon E, Flor, Herta, Forstner, Andreas J, Francks, Clyde, Franke, Barbara, Glahn, David C, Gollub, Randy L, Grabe, Hans J, Colodro-Conde, Lucía, Cannon, Dara M, Gruber, Oliver, Håberg, Asta K, Hariri, Ahmad R, Hartman, Catharina A, Hashimoto, Ryota, Heinz, Andreas, Henskens, Frans A, Hillegers, Manon H J, Hoekstra, Pieter J, Holmes, Avram J, Chakravarty, Mallar, Hong, L Elliot, Hopkins, William D, Hulshoff Pol, Hilleke E, Jernigan, Terry L, Jönsson, Erik G, Kahn, René S, Kennedy, Martin A, Kircher, Tilo T J, Kochunov, Peter, Kwok, John B J, Chen, Qiang, Le Hellard, Stephanie, Loughland, Carmel M, Martin, Nicholas G, Martinot, Jean-Luc, McDonald, Colm, McMahon, Katie L, Meyer-Lindenberg, Andreas, Michie, Patricia T, Morey, Rajendra A, Mowry, Bryan, Cheung, Joshua W, Nyberg, Lars, Oosterlaan, Jaap, Ophoff, Roel A, Pantelis, Christos, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W J H, Polderman, Tinca J C, Posthuma, Danielle, Rietschel, Marcella, Couvy-Duchesne, Baptiste, Roffman, Joshua L, Rowland, Laura M, Sachdev, Perminder S, Sämann, Philipp G, Schall, Ulrich, Schumann, Gunter, Scott, Rodney J, Sim, Kang, Sisodiya, Sanjay M, Smoller, Jordan W, Dale, Anders M, Sommer, Iris E, St Pourcain, Beate, Stein, Dan J, Toga, Arthur W, Trollor, Julian N, Van der Wee, Nic J A, van 't Ent, Dennis, Völzke, Henry, Walter, Henrik, Weber, Bernd, Dalvie, Shareefa, Weinberger, Daniel R, Wright, Margaret J, Zhou, Juan, Stein, Jason L, Thompson, Paul M, Medland, Sarah E, Consortium, Enhancing NeuroImaging Genetics through Meta-Analysis, Witte, A Veronica, Darin, Abigail, Fleisher, Adam, de Araujo, Tânia K, Pierce, Aimee, Mintz, Akiva, Lerner, Alan, Reith, Alastair D, Hofman, Albert, Espay, Alberto, Ihlenfeld, Albrecht, Ing, Alex, Iranzo, Alex, Beiser, Alexa S, de Zubicaray, Greig I, Norbash, Alexander, Barbot, Alexis, Rudolph, Alice, Portillo, Alicia, Chalker, Alison, Levey, Allan I, Rosen, Allyson, Smith, Amanda, Catafau, Ana, de Zwarte, Sonja M C, Ulysse, Anaztasia, Uitterlinden, André G, Becker, Andreas, Budson, Andrew E, Kertesz, Andrew, Siderowf, Andrew, Bralten, Janita, den Braber, Anouk, Singleton, Andrew, James, Angela, Oliver, Angela, Mishra, Aniket, Hake, Ann Marie, Burke, Anna, Sarrael, Antero, Porsteinsson, Anton P, Stringaris, Argyris, McCoy, Arita, Doan, Nhat Trung, Villringer, Arno, Lenahan, Art, Toga, Arthur, Bokde, Arun, Rawlins, Ashlee, Lamb, Ashley, Lee, Athena, Raj, Balebail Ashok, Tran, Baochan, Dohm, Katharina, Ruggeri, Barbara, Saba, Barbara, Lane, Barton, Yanez, Beatriz, Ances, Beau, Dunlop, Becky, Mudge, Benita, Ravina, Bernard, Ittermann, Bernd, Ehrlich, Stefan, van Noort, Betteke, Lind, Betty, Shah, Bina, Stefanovic, Bojana, Goldstein, Bonnie S, Bonakdarpour, Borna, Matthews, Brandy R, Borowski, Bret, Ott, Brian R, Reynolds, Brigid, Engelbrecht, Hannah-Ruth, Mollenhauer, Brit, Miller, Bruce L, Psaty, Bruce M, Spann, Bryan M, Sadowsky, Carl, Linder, Carly, Franz, Carol E, Tanner, Caroline, Kopil, Catherine, Thomas, Cathi-Ann, Erk, Susanne, Ward, Chad, Bernick, Charles, Smith, Charles D, DeCarli, Charles, Caspell, Chelsea, Deeley, Cheryl, Riordan, Cheryl, Mathis, Chet, Onyike, Chiadi, Heyn, Chris Chinthaka, Fan, Chun Chieh, Hosein, Chris, Leach, Christi, Bÿchel, Christian, Gigliotti, Christina, Hunter, Christine, Belden, Christine M, Tzourio, Christophe, Coffey, Christopher, van Dyck, Christopher H, Clark, Christopher M, Fedko, Iryna O, Wu, Chuang-Kuo, Albers, Colleen S, Chu, Congying, Brand, Connie, Isensee, Corinna, van Duijn, Cornelia M, Bishop, Courtney, Bodge, Courtney, Foley, Sonya F, Tatsuoka, Curtis, Casaceli, Cynthia, Carlsson, Cynthia M, Mathews, Dana, D'Agostino, Daniel, Silverman, Daniel H S, Marson, Daniel, Berg, Daniela, Harvey, Danielle, Jennings, Danna, Ford, Judith M, Wolk, David A, Goldstein, David B, Bachman, David, Brooks, David, Clark, David, Geldmacher, David, Hart, David, Holtzman, David, Jones, David, Hibar, Derrek P, Fukunaga, Masaki, Knopman, David, Hewitt, David L, Perry, David, Russell, David, Standaert, David, Winkfield, David, Green, Davis Robert C, Fontaine, Deborah, Miller, Delwyn D, Gessert, Devon, Garrett, Melanie E, Kerwin, Diana, Willeke, Diana, Drost, Dick, Papadopoulos, Dimitri, Rowe, Dominic, Simpson, Donna M, Muni, Donna, Galasko, Douglas, Scharre, Douglas W, Fillmer, Ariane, Ge, Tian, Bartha, Rob, Celmins, Dzintra, Zimmerman, Earl A, Teng, Edmond, Tolosa, Eduardo, Coleman, Edward, Zamrini, Edward, Mitsis, Effie, Finger, Elizabeth, Giddaluru, Sudheer, Oates, Elizabeth, Sosa, Elizabeth, Woo, Ellen, Rogalski, Emily, Lethbridge, Emma, Dooley, Eoin, Foster, Eric, Reiman, Eric M, Quinlan, Erin Burke, Goldman, Aaron L, Franklin, Erin, Heinzen, Erin L, Fletcher, Evan, Sprenger, Fabienne, Crivello, Fabrice, Biondo, Francesca, Parfitt, Francine, Hefti, Franz, Beyer, Frauke, Nees, Frauke, Green, Melissa J, Leonard, Gabriel, Robert, Gabriel, Thai, Gaby, Marshall, Gad A, Barker, Gareth, Conrad, Gary, Tremont, Geoffrey, Bartzokis, George, Groenewold, Nynke A, Hsiung, Ging-Yuek Robin, Malferrari, Giulia, Chiang, Gloria, Pearlson, Godfrey D, Liang, Grace, Jicha, Greg, Sorensen, Greg, Todd, Gretchen, Jimenez, Gustavo, Grotegerd, Dominik, Zare, Habil, Grabe, Hans Jörgen, Vanderswag, Helen, Schmidt, Helena, Venkov, Heli, Lemaitre, Hervé, Gurholt, Tiril P, Grossman, Hillel, Shill, Holly, Soares, Holly, Lin, Honghuang, Capote, Horacio, Bergman, Howard, Chertkow, Howard, Feldman, Howard, Fillit, Howard, Rosen, Howard J, Gutman, Boris A, Koleva, Hristina, Fernandez, Hubert, Garavan, Hugh, Shim, Hyungsub, Grachev, Igor D, Richard, Irene, Filippi, Irina, Rachinsky, Irina, Wurster, Isabel, Lind, Penelope A, Hansell, Narelle K, Mintzer, Jacobo, Ziolkowski, Jaimie, Brewer, James, Lah, James J, Leverenz, James, Becker, James T, Tetrud, James, Singleton-Garvin, Jamika, Egebjerg, Jan, Cellar, Janet S, Harris, Mathew A, Pentilla, Jani, Brosch, Jared R, Tinklenberg, Jared, Karlawish, Jason H, Meyer, Javier Villanueva, Himali, Jayandra J, Poline, Jean-Baptiste, Gunter, Jeff, Kaye, Jeffrey A, Harrison, Marc B, Dalley, Jeffrey, Burns, Jeffrey M, Petrella, Jeffrey R, Mule, Jennifer, Salazar, Jennifer, Rotter, Jerome I, Yesavage, Jerome, Cedarbaum, Jesse, Jiang, Jiyang, Haswell, Courtney C, Allard, Joanne, Lord, Joanne L, Hetelle, Joel, Kwok, John B, Brockington, John, Morris, John C, Hsiao, John, Morris, John, Olichney, John, Trojanowki, John Q, Hauser, Michael, Rogers, John, Seibyl, John, Yankey, Jon, Dubow, Jordan S, Jankovic, Joseph, Quinn, Joseph, Kass, Joseph S, Taylor, Joy L, Heidebrink, Judith L, Herms, Stefan, Trollor, Julian, Fröhner, Juliane, Anderson, Karen, Blank, Karen, Crawford, Karen, Smith, Karen Ekstam, Bell, Karen L, Williams, Karen, Kieburtz, Karl, Heslenfeld, Dirk J, Gauss, Katharina, Gloer, Katherine, Johnson, Kathleen, Tingus, Kathleen, DeMarco, Kathryn, Sink, Kaycee M, Hawkins, Keith A, Johnson, Keith A, Kantarci, Kejal, Ho, New Fei, Faber, Kelley, Harless, Kelly, Makino, Kelly M, Marek, Kenneth, Spicer, Kenneth, Shianna, Kevin, Chen, Kewei, Nam, Ki Won, Martin, Kim, Poki-Walker, Kim, Hoehn, David, Seppi, Klaus, Johnson, Kris, Fargher, Kristin, Lipowski, Kristine, Espay, Kristy, Womack, Kyle, Chahine, Lama, Flashman, Laura A, Daedelow, Laura, Hoffmann, Per, Leary, Laura, Beckett, Laurel, Honig, Lawrence S, Thal, Leon, Shaw, Leslie M, Kuller, Lew, Apostolova, Liana, Teodoro, Liberty, Rees, Linda, Pizzagalli, Fabrizio, Holleran, Laurena, Lewis, Lindsay, Hergesheimer, Lindsey, Silbert, Lisa C, Ravdin, Lisa, Taylor-Reinwald, Lisa, Uribe, Liz, Schneider, Lon S, Daiello, Lori A, Richer, Louis, Poustka, Luise, Hoogman, Martine, Pirpamer, Lukas, Mesulam, M Marcel, Ismail, M Saleem, Ranola, Madelaine, Korecka, Magdalena, Raichle, Marc, Seltzer, Marc, van der Brug, Marcel, Hottenga, Jouke-Jan, Mesulam, Marek-Marsel, Carrillo, Maria, Carroll, Maria, Knol, Maria J, Kataki, Maria, Greig-Custo, Maria T, Paillere, Marie-Laure, Albert, Marilyn, Love, Marissa Natelson, Ikeda, Masashi, Mintun, Mark A, Frasier, Mark, Logue, Mark, Minton, Mark, Loeffler, Markus, Scholz, Markus, Baca, Marne, Farlow, Martin R, Sadowski, Martin, Janowitz, Deborah, Creech, Mary L, Hynes, Mary L, Quiceno, Mary, Oakley, MaryAnn, Harris, Mat, Senjem, Matt, Bernstein, Matthew, Panizzon, Matthew S, Stern, Matthew, Becerra, Mauricio, Jansen, Iris E, Witbracht, Megan, Vernooij, Meike W, Brandabur, Melanie, Keltz, Melanie, Lamar, Melissa, Yang, Mia, Ahlijanian, Michael, Borrie, Michael, Neale, Michael C, Donohue, Michael, Jia, Tianye, Lyons, Michael J, Lin, Michael, Rapp, Michael, Smolka, Michael, Weiner, Michael W, Weiner, Michael, Figurski, Michal, Perron, Michel, Assaly, Michele, Luciano, Michelle, Jockwitz, Christiane, Rainka, Michelle, Dang, Mimi, Sheikh, Mohammed O, Ghanbari, Mohsen, Gaikwad, Mrunalini, Chowdhury, Munir, Trncic, Nadira, Amin, Najaf, Johnson, Nancy, Kanai, Ryota, Kowalksi, Nancy, Monahan, Nancy, Gillespie, Nathan A, Pacini, Nathaniel, Buckholtz, Neil, Kowall, Neil, Graff-Radford, Neill R, Fox, Nick, Pavese, Nicola, Karama, Sherif, Cairns, Nigel J, Schuff, Norbert, Foster, Norm, Relkin, Norman, Oyonumo, Ntekim E, Pomara, Nunzio, James, Olga, Ogunlana, Olu, Ching, Christopher R K, Kasperaviciute, Dalia, Carmichael, Owen, Doraiswamy, P Murali, Casalin, Paola, Barone, Paolo, Fatica, Parianne, Conrod, Patricia, Johnson, Patricia Lynn, Samuels, Patricia, Aisen, Paul, Malloy, Paul, Kaufmann, Tobias, Thompson, Paul, Ogrocki, Paula, Bezivin-Frere, Pauline, Maillard, Pauline, Fontoura, Paulo, Taylor, Peggy, Hogarth, Penelope, Gowland, Penny, Davies, Peter, Kelly, Sinead, Hardy, Peter, Snyder, Peter J, Snyder, Peter, Amouyel, Philippe, Muglia, Pierandrea, Tariot, Pierre, Lu, Po H, Varma, Pradeep, Vemuri, Prashanthi, Kikuchi, Masataka, Doody, Rachelle S, Carter, Raina, Shah, Raj C, Griffith, Randall, Yeh, Randy, Duara, Ranjan, Tarawneh, Rawan, James, Raymond, Turner, Raymond Scott, Klein, Marieke, Hernando, Raymundo, Silverstein, Rebecca, Sperling, Reisa A, Wilson, Renee, Carson, Richard E, Frank, Richard, El Khouli, Riham, Koeppe, Robert A, Santulli, Robert B, Knapp, Michael, Hauser, Robert, Umek, Robert, Radtke, Rodney, Killiany, Ronald, Petersen, Ronald, Rodriguez, Rosemarie, Miranda, Ruben, Knodt, Annchen R, Bruehl, Ruediger, Xia, Rui, Swerdlow, Russell H, Ottmann, Ruth, Millenet, Sabina, Borges-Neto, Salvador, Frank, Samuel, Black, Sandra, Weintraub, Sandra, Obradov, Sanja, Krämer, Bernd, Asthana, Sanjay, Vaishnavi, Sanjeev, Dolen, Sara, Mason, Sara S, Hohmann, Sarah, Kremen, Sarah, Miller, Sarah, Walter, Sarah, Herring, Scott, Neu, Scott, Lam, Max, Aydin, Semiha, Ahmad, Shahzad, Harlan, Sherry, Sirrel, Sherye A, Lasch, Shirley, Hu, Shu-Ching, Li, Shuo, Kittur, Smita, Chowdhury, Sohini, Lancaster, Thomas M, Pawluczyk, Sonia, Maingault, Sophie, Schneider, Stacy, Seiler, Stephan, Guthrie, Stephanie, Kielb, Stephanie, Reeder, Stephanie, Correia, Stephen, Pasternak, Stephen, McMahon, Mary Agnes B, Lee, Phil H, Salloway, Stephen, Johnson, Sterling, Williams, Steve, Chao, Steven, Arnold, Steven E, Paul, Steven, Potkin, Steven, Factor, Stewart, Isaacson, Stuart, Lett, Tristram A, Kim, Sungeun, Ainscough, Susan, Schultz, Susan K, Landau, Susan, Mendick, Susan, Rountree, Susan, Ostrowizki, Suzanne, Veillette, Suzanne, van der Lee, Sven J, Desrivieres, Sylvane, Lewis, Lindsay B, Lee, T-Y, Simuni, Tanya, Foroud, Tatiana, Foroud, Tatiana M, Wong, Terence Z, Villena, Teresa, Comery, Thomas, Obisesan, Thomas O, Lopes-Cendes, Iscia, Banaschewski, Tobias, Sherer, Todd, Montine, Tom, Paus, Tomáš, Robbins, Trevor, Bromberg, Uli, Völker, Uwe, Pavlik, Valory, Arnedo, Vanessa, Kiyasova, Vera, Bates, Vernice, Logovinsky, Veronika, Sossi, Vesna, Shibley, Victoria, Frouin, Vincent, Lee, Virginia, Poewe, Werner, Jagust, William, Brooks, William M, Macciardi, Fabio, Pavlosky, William, Potter, William, Kremen, William S, Longstreth, William T, Niessen, Wiro J, Jian, Xueqiu, Stern, Yaakov, Saba, Yasaman, Cabrera, Yuliana, Grimmer, Yvonne, Marquand, Andre F, Khachaturian, Zaven, Mari, Zoltan, Mathias, Samuel R, Melzer, Tracy R, Milaneschi, Yuri, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Movement Disorder (MD), Alzheimer’s Disease Neuroimaging Initiative, CHARGE Consortium, EPIGEN Consortium, IMAGEN Consortium, SYS Consortium, Parkinson’s Progression Markers Initiative, Stochastics, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, Science and Society, Cognitive Psychology, IBBA, APH - Personalized Medicine, Complex Trait Genetics, APH - Methodology, Clinical Neuropsychology, Sociology and Social Gerontology, Amsterdam Neuroscience - Complex Trait Genetics, RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, Klinische Genetica, RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA Klinische Genetica (5), Neurology, Psychiatry, Pediatric surgery, Amsterdam Reproduction & Development (AR&D), Human genetics, APH - Digital Health, Psychology, Precision Medicine Institute of Psychiatry, Child and Adolescent Psychiatry / Psychology, Radiology & Nuclear Medicine, Clinical Genetics, Epidemiology, Medical Informatics, Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Neurodegeneratives Diseases Institute (IMN-UMR CNRS 5293), Centre National de la Recherche Scientifique (CNRS), General Paediatrics, ARD - Amsterdam Reproduction and Development, Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay

Subjects
0301 basic medicine, Netherlands Twin Register (NTR), [SDV]Life Sciences [q-bio], LOCI, Genome-wide association study, Brain mapping, 0302 clinical medicine, Cognition, Cortex (anatomy), ComputingMilieux_MISCELLANEOUS, Cerebral Cortex, 0303 health sciences, Brain Mapping, Multidisciplinary, COMMON VARIANTS, Parkinson Disease, Organ Size, Central sulcus, Magnetic Resonance Imaging, medicine.anatomical_structure, Cerebral cortex, Neuroinformatics, EXPRESSION, endocrine system, central sulcus, SURFACE-AREA, Biology, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Genetic variation, medicine, Attention deficit hyperactivity disorder, Humans, General, Gene, METAANALYSIS, 030304 developmental biology, Progenitor, CORTICAL SULCI, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Genetic variants, Genetic Variation, Attention Deficit Disorder with Hyperactivity, Genetic Loci, Genome-Wide Association Study, functional annotation, medicine.disease, Genetic architecture, 030104 developmental biology, Evolutionary biology, OBSERVER-INDEPENDENT CHARACTERIZATION, Multiple comparisons problem, ddc:320, genome-wide association, Neuroscience, 030217 neurology & neurosurgery
Abstract

Enhancing NeuroImaging Genetics through Meta-Analysis Consortium (ENIGMA)—Genetics working group., The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.

Published
2020

12. The Parkinson Progression Marker Initiative (PPMI)

Author

Marek, Kenneth, Jennings, Danna, Lasch, Shirley, Siderowf, Andrew, Tanner, Caroline, Simuni, Tanya, Coffey, Chris, Kieburtz, Karl, Flagg, Emily, Chowdhury, Sohini, Poewe, Werner, Mollenhauer, Brit, Klinik, Paracelsus-Elena, Sherer, Todd, Frasier, Mark, Meunier, Claire, Rudolph, Alice, Casaceli, Cindy, Seibyl, John, Mendick, Susan, Schuff, Norbert, Zhang, Ying, Toga, Arthur, Crawford, Karen, Ansbach, Alison, De Blasio, Pasquale, Piovella, Michele, Trojanowski, John, Shaw, Les, Singleton, Andrew, Hawkins, Keith, Eberling, Jamie, Brooks, Deborah, Russell, David, Leary, Laura, Factor, Stewart, Sommerfeld, Barbara, Hogarth, Penelope, Pighetti, Emily, Williams, Karen, Standaert, David, Guthrie, Stephanie, Hauser, Robert, Delgado, Holly, Jankovic, Joseph, Hunter, Christine, Stern, Matthew, Tran, Baochan, Leverenz, Jim, Baca, Marne, Frank, Sam, Thomas, Cathi-Ann, Richard, Irene, Deeley, Cheryl, Rees, Linda, Sprenger, Fabienne, Lang, Elisabeth, Shill, Holly, Obradov, Sanja, Fernandez, Hubert, Winters, Adrienna, Berg, Daniela, Gauss, Katharina, Galasko, Douglas, Fontaine, Deborah, Mari, Zoltan, Gerstenhaber, Melissa, Brooks, David, Malloy, Sophie, Barone, Paolo, Longo, Katia, Comery, Tom, Ravina, Bernard, Grachev, Igor, Gallagher, Kim, Collins, Michelle, Widnell, Katherine L., Ostrowizki, Suzanne, Fontoura, Paulo, Ho, Tony, Luthman, Johan, Brug, Marcel van der, Reith, Alastair D., and Taylor, Peggy

Published
2011
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13. Cognition among individuals along a spectrum of increased risk for Parkinson’s disease

Author

Chahine, Lana M., Urbe, Liz, Caspell-Garcia, Chelsea, Aarsland, Dag, Alcalay, Roy Nissim, Barone, Paolo, Burn, David, Espay, Alberto J., Hamilton, Jamie L., Hawkins, Keith A., Lasch, Shirley, Leverenz, James B., Litvan, Irene, Richard, Irene, Siderowf, Andrew, Coffey, Christopher S., Simuni, Tanya, Weintraub, Daniel, and Parkinson’s Progression Markers Initiative

Subjects
Cognition, Neurology, Parkinson's disease--Patients, Cognitive neuroscience, Diseases--Risk factors
Abstract

Introduction Several characteristics associated with increased risk for Parkinson’s disease (PD) have been identified, including specific genotypes and various non-motor symptoms. Characterizing non-motor features, such as cognitive abilities, among individuals considered at-risk for PD is essential to improving prediction of future neurodegeneration. Methods Participants belonging to the following cohorts of the Parkinson Progression Markers Initiative (PPMI) study were included: de novo PD with dopamine transporter binding deficit (n = 423), idiopathic REM sleep behavior disorder (RBD, n = 39), hyposmia (n = 26) and non-PD mutation carrier (NMC; Leucine-rich repeat kinase 2 (LRRK2) G2019S (n = 88) and glucocerebrosidase (GBA) gene (n = 38) mutations)). Inclusion criteria enriched the RBD and hyposmia cohorts, but not the NMC cohort, with individuals with dopamine transporter binding deficit. Baseline neuropsychological performance was compared, and analyses were adjusted for age, sex, education, and depression. Results The RBD cohort performed significantly worse than the hyposmia and NMC cohorts on Symbol Digit Modality Test (mean (SD) 32.4 (9.16) vs. 41.8 (9.98), p = 0.002 and vs. 45.2 (10.9), p

Published
2018
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14. Finding useful biomarkers for Parkinson’s disease

Author

Chen-Plotkin, Alice S., primary, Albin, Roger, additional, Alcalay, Roy, additional, Babcock, Debra, additional, Bajaj, Vikram, additional, Bowman, Dubois, additional, Buko, Alex, additional, Cedarbaum, Jesse, additional, Chelsky, Daniel, additional, Cookson, Mark R., additional, Dawson, Ted M., additional, Dewey, Richard, additional, Foroud, Tatiana, additional, Frasier, Mark, additional, German, Dwight, additional, Gwinn, Katrina, additional, Huang, Xuemei, additional, Kopil, Catherine, additional, Kremer, Thomas, additional, Lasch, Shirley, additional, Marek, Ken, additional, Marto, Jarrod A., additional, Merchant, Kalpana, additional, Mollenhauer, Brit, additional, Naito, Anna, additional, Potashkin, Judith, additional, Reimer, Alyssa, additional, Rosenthal, Liana S., additional, Saunders-Pullman, Rachel, additional, Scherzer, Clemens R., additional, Sherer, Todd, additional, Singleton, Andrew, additional, Sutherland, Margaret, additional, Thiele, Ines, additional, van der Brug, Marcel, additional, Van Keuren-Jensen, Kendall, additional, Vaillancourt, David, additional, Walt, David, additional, West, Andrew, additional, and Zhang, Jing, additional

Published
2018
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15. Baseline prevalence and longitudinal evolution of non-motor symptoms in early Parkinson’s disease: the PPMI cohort

Author

Simuni, Tanya, primary, Caspell-Garcia, Chelsea, additional, Coffey, Christopher S, additional, Weintraub, Daniel, additional, Mollenhauer, Brit, additional, Lasch, Shirley, additional, Tanner, Caroline M, additional, Jennings, Danna, additional, Kieburtz, Karl, additional, Chahine, Lana M, additional, and Marek, Kenneth, additional

Published
2017
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16. Longitudinal assessment of excessive daytime sleepiness in early Parkinson’s disease

Author

Amara, Amy W, primary, Chahine, Lama M, additional, Caspell-Garcia, Chelsea, additional, Long, Jeffrey D, additional, Coffey, Christopher, additional, Högl, Birgit, additional, Videnovic, Aleksandar, additional, Iranzo, Alex, additional, Mayer, Geert, additional, Foldvary-Schaefer, Nancy, additional, Postuma, Ron, additional, Oertel, Wolfgang, additional, Lasch, Shirley, additional, Marek, Ken, additional, and Simuni, Tanya, additional

Published
2017
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17. Feasibility and Safety of Multisite Tissue and Biofluid Sampling for Synuclein in Parkinson’s Disease: The Systemic Synuclein Sampling Study (S4) (P1.013)

Author

Linder, Carly, primary, Coffey, Christopher, additional, Beach, Thomas, additional, Foroud, Tatiana, additional, Adler, Charles, additional, Riss, Holly, additional, Ecklund, Dixie, additional, Caspell-Garcia, Chelsea, additional, Dave, Kuldip, additional, Deshpande, Sampada, additional, Lasch, Shirley, additional, Arnedo, Vanessa, additional, Riley, Lindsey, additional, Jennings, Danna, additional, Mollenhauer, Brit, additional, and Chahine, Lana, additional

Published
2017
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18. Diagnosis of Parkinson's disease on the basis of clinical and genetic classification: A population-based modelling study

Author

Nalls, Mike A, McLean, Cory Y, Hardy, John, Seppi, Klaus, Reiter, Eva, Shill, Holly, Fernandez, Hubert, Ahmed, Anwar, Berg, Daniela, Wurster, Isabel, Mari, Zoltan, Brooks, David, Pavese, Nicola, Gasser, Thomas, Barone, Paolo, Isaacson, Stuart, Espay, Alberto, Rowe, Dominic, Brandabur, Melanie, Tetrud, James, Liang, Grace, Marder, Karen, Corvol, Jean-Christophe, Martí Masso, Jose Felix, Brice, Alexis, Tolosa, Eduardo, Aasly, Jan O, Giladi, Nir, Stefanis, Leonidas, Leary, Laura, Riordan, Cheryl, Rees, Linda, Sommerfeld, Barbara, Wood-Siverio, Cathy, Portillo, Alicia, Price, T Ryan, Lenahan, Art, Williams, Karen, Guthrie, Stephanie, Rawlins, Ashlee, Harlan, Sherry, Hunter, Christine, Tran, Baochan, Darin, Abigail, Linder, Carly, Todd, Gretchen, Nicolas, Aude, Thomas, Cathi-Ann, James, Raymond, Deeley, Cheryl, Bishop, Courtney, Sprenger, Fabienne, Willeke, Diana, Obradov, Sanja, Mule, Jennifer, Monahan, Nancy, Gauss, Katharina, Keller, Margaux F, Comyns, Kathleen, Fontaine, Deborah, Gigliotti, Christina, McCoy, Arita, Dunlop, Becky, Shah, Bina, Ainscough, Susan, James, Angela, Silverstein, Rebecca, Espay, Kristy, Molony, Cliona, Ranola, Madelaine, Santana, Helen M, Ngono, Nelly, Rezola, Elisabet, Rolan, Delores Vilas, Waro, Bjorg, Mirlman, Anat, Stamelou, Maria, Comery, Thomas, Papapetropoulos, Spyros, Gibbs, J Raphael, Ravina, Bernard, Grachev, Igor D, Dubow, Jordan S, Ahlijanian, Michael, Soares, Holly, Ostrowizki, Suzanne, Fontoura, Paulo, Chalker, Alison, Hewitt, David L, van der Brug, Marcel, Chen-Plotkin, Alice, Reith, Alastair D, Taylor, Peggy, Egebjerg, Jan, Minton, Mark, Siderowf, Andrew, Muglia, Pierandrea, Umek, Robert, Catafau, Ana, Suh, Eunran, Rick, Jacqueline, Letson, Christopher, Fiandaca, Massimo S, Mapstone, Mark, Federoff, Howard J, Noyce, Alastair J, Morris, Huw, Van Deerlin, Vivianna M, Weintraub, Daniel, Zabetian, Cyrus, Hernandez, Dena G, Eberly, Shirley, Lesage, Suzanne, Mullins, Meghan, Conley, Emily Drabant, Northover, Carrie A M, Frasier, Mark, Marek, Ken, Day-Williams, Aaron G, Stone, David J, Ioannidis, John P A, Singleton, Andrew B, Hutten, Samantha J, investigators, Parkinson's Disease Biomarkers Program and Parkinson's Progression Marker Initiative, Bowman, Dubois, Dawson, Ted, Dewey, Richard, German, Dwight Charles, Huang, Xuemei, Petyuk, Vladislav, Scherzer, Clemens, Vaillancourt, David, Gwinn, Katrina, West, Andrew, Zhang, Jing, Marek, Kenneth, Jennings, Danna, Lasch, Shirley, Tanner, Caroline, Simuni, Tanya, Coffey, Christopher, Kieburtz, Karl, Wilson, Renee, Sutherland, Margaret, Poewe, Werner, Mollenhauer, Brit, Galasko, Douglas, Foroud, Tatiana, Sherer, Todd, Chowdhury, Sohini, Kopil, Catherine, Arnedo, Vanessa, Casaceli, Cynthia, Martinez, Maria, Seibyl, John, Mendick, Susan, Schuff, Norbert, Caspell, Chelsea, Uribe, Liz, Foster, Eric, Gloer, Katherine, Yankey, Jon, Toga, Arthur, Crawford, Karen, Heutink, Peter, Smith, Danielle Elise, Casalin, Paola, Malferrari, Giulia, Trojanowski, John, Shaw, Les, Singleton, Andrew, Halter, Cheryl, Russell, David, Factor, Stewart, Hogarth, Penelope, Williams, Nigel M, Standaert, David, Hauser, Robert, Jankovic, Joseph, Stern, Matthew, Chahine, Lama, Hu, Shu-Ching, Frank, Samuel, Trenkwalder, Claudia, Oertel, Wolfgang, and Richard, Irene

Subjects
Male, Aging, Parkinson's disease, Genome-wide association study, Disease, Neurodegenerative, Cohort Studies, genetics [Parkinson Disease], Models, 2.1 Biological and endogenous factors, Family history, Aetiology, education.field_of_study, screening and diagnosis, Parkinson's Disease, Aged, Disease Progression, Female, Humans, Middle Aged, Parkinson Disease, Prodromal Symptoms, Models, Statistical, Neurology (clinical), Statistical, Detection, Cohort, Neurological, Biomarker (medicine), diagnosis [Parkinson Disease], Cohort study, 4.2 Evaluation of markers and technologies, medicine.medical_specialty, Population, Clinical Sciences, Parkinson's Disease Biomarkers Program and Parkinson's Progression Marker Initiative investigators, Article, Clinical Research, Internal medicine, medicine, ddc:610, education, Neurology & Neurosurgery, business.industry, Prevention, Neurosciences, medicine.disease, Brain Disorders, 4.1 Discovery and preclinical testing of markers and technologies, Good Health and Well Being, Physical therapy, business
Abstract

Summary Background Accurate diagnosis and early detection of complex diseases, such as Parkinson's disease, has the potential to be of great benefit for researchers and clinical practice. We aimed to create a non-invasive, accurate classification model for the diagnosis of Parkinson's disease, which could serve as a basis for future disease prediction studies in longitudinal cohorts. Methods We developed a model for disease classification using data from the Parkinson's Progression Marker Initiative (PPMI) study for 367 patients with Parkinson's disease and phenotypically typical imaging data and 165 controls without neurological disease. Olfactory function, genetic risk, family history of Parkinson's disease, age, and gender were algorithmically selected by stepwise logistic regression as significant contributors to our classifying model. We then tested the model with data from 825 patients with Parkinson's disease and 261 controls from five independent cohorts with varying recruitment strategies and designs: the Parkinson's Disease Biomarkers Program (PDBP), the Parkinson's Associated Risk Study (PARS), 23andMe, the Longitudinal and Biomarker Study in PD (LABS-PD), and the Morris K Udall Parkinson's Disease Research Center of Excellence cohort (Penn-Udall). Additionally, we used our model to investigate patients who had imaging scans without evidence of dopaminergic deficit (SWEDD). Findings In the population from PPMI, our initial model correctly distinguished patients with Parkinson's disease from controls at an area under the curve (AUC) of 0·923 (95% CI 0·900–0·946) with high sensitivity (0·834, 95% CI 0·711–0·883) and specificity (0·903, 95% CI 0·824–0·946) at its optimum AUC threshold (0·655). All Hosmer-Lemeshow simulations suggested that when parsed into random subgroups, the subgroup data matched that of the overall cohort. External validation showed good classification of Parkinson's disease, with AUCs of 0·894 (95% CI 0·867–0·921) in the PDBP cohort, 0·998 (0·992–1·000) in PARS, 0·955 (no 95% CI available) in 23andMe, 0·929 (0·896–0·962) in LABS-PD, and 0·939 (0·891–0·986) in the Penn-Udall cohort. Four of 17 SWEDD participants who our model classified as having Parkinson's disease converted to Parkinson's disease within 1 year, whereas only one of 38 SWEDD participants who were not classified as having Parkinson's disease underwent conversion (test of proportions, p=0·003). Interpretation Our model provides a potential new approach to distinguish participants with Parkinson's disease from controls. If the model can also identify individuals with prodromal or preclinical Parkinson's disease in prospective cohorts, it could facilitate identification of biomarkers and interventions. Funding National Institute on Aging, National Institute of Neurological Disorders and Stroke, and the Michael J Fox Foundation.

Published
2015

19. Novel recruitment strategy to enrich for LRRK2 mutation carriers.

Author

Foroud, Tatiana, Smith, Danielle, Jackson, Jacqueline, Verbrugge, Jennifer, Halter, Cheryl, Wetherill, Leah, Sims, Katherine, Xin, Winnie, Arnedo, Vanessa, Lasch, Shirley, and Marek, Kenneth

Subjects
PARKINSON'S disease patients, PARKINSON'S disease & genetics, DARDARIN, PARKINSON'S disease diagnosis, GENETIC mutation, GENETIC testing
Abstract

The LRRK2 G2019S mutation is found at higher frequency among Parkinson disease ( PD) patients of Ashkenazi Jewish ( AJ) ancestry. This study was designed to test whether an internet-based approach could be an effective approach to screen and identify mutation carriers. Individuals with and without PD of AJ ancestry were recruited and consented through an internet-based study website. An algorithm was applied to a series of screening questions to identify individuals at increased risk to carry the LRRK2 G2019S mutation. About 1000 individuals completed the initial screening. Around 741 qualified for mutation testing and 650 were tested. Seventy-two individuals carried at least one LRRK2 G2019S mutation; 38 with PD (12.5%) and 34 without (10.1%). Among the AJ PD participants, each affected first-degree relative increased the likelihood the individual was LRRK2+ [OR = 4.7; 95% confidence interval = (2.4-9.0)]. The same was not observed among the unaffected AJ subjects ( P = 0.11). An internet-based approach successfully screened large numbers of individuals to identify those with risk factors increasing the likelihood that they carried a LRRK2 G2019S mutation. A similar approach could be implemented in other disorders to identify individuals for clinical trials, biomarker analyses and other types of research studies. [ABSTRACT FROM AUTHOR]

Published
2015
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20. BR96 conjugates of highly potent anthracyclines

Author

King, H.Dalton, primary, Staab, Andrew J., additional, Pham-Kaplita, Kahnie, additional, Yurgaitis, Derek, additional, Firestone, Raymond A., additional, Lasch, Shirley J., additional, and Trail, Pamela A., additional

Published
2003
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22. Cathepsin B-Labile Dipeptide Linkers for Lysosomal Release of Doxorubicin from Internalizing Immunoconjugates: Model Studies of Enzymatic Drug Release and Antigen-Specific In Vitro Anticancer Activity

Author

Dubowchik, Gene M., primary, Firestone, Raymond A., additional, Padilla, Linda, additional, Willner, David, additional, Hofstead, Sandra J., additional, Mosure, Kathleen, additional, Knipe, Jay O., additional, Lasch, Shirley J., additional, and Trail, Pamela A., additional

Published
2002
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