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1. Longitudinal Measurements of Glucocerebrosidase activity in Parkinson’s patients

Author

Alcalay, Roy N, Wolf, Pavlina, Chiang, Ming Sum Ruby, Helesicova, Karolina, Zhang, Xiaokui Kate, Merchant, Kalpana, Hutten, Samantha J, Scherzer, Clemens, Caspell‐Garcia, Chelsea, Blauwendraat, Cornelis, Foroud, Tatiana, Nudelman, Kelly, Gan‐Or, Ziv, Simuni, Tanya, Chahine, Lana M, Levy, Oren, Zheng, Dandi, Li, Sardi, Sergio Pablo, Marek, Kenneth, Siderowf, Andrew, Seibyl, John, Coffey, Christopher, Tanner, Caroline, Tosun‐Turgut, Duygu, Shaw, Leslie M, Trojanowski, John Q, Singleton, Andrew, Kieburtz, Karl, Toga, Arthur, Mollenhauer, Brit, Galasko, Douglas, Poewe, Werner, Poston, Kathleen, Bressman, Susan, Reimer, Alyssa, Arnedo, Vanessa, Clark, Adrienne, Frasier, Mark, Kopil, Catherine, Chowdhury, Sohini, Sherer, Todd, Casaceli, Cynthia, Dorsey, Ray, Wilson, Renee, Mahes, Sugi, Salerno, Christina, Crawford, Karen, Casalin, Paola, Malferrari, Giulia, Weisz, Mali Gani, Orr‐Urtreger, Avi, Montine, Thomas, Baglieri, Chris, Christini, Amanda, Russell, David, Dahodwala, Nabila, Giladi, Nir, Factor, Stewart, Hogarth, Penelope, Standaert, David, Hauser, Robert, Jankovic, Joseph, Saint‐Hilaire, Marie, Richard, Irene, Shprecher, David, Fernandez, Hubert, Brockmann, Katrina, Rosenthal, Liana, Barone, Paolo, Espay, Alberto, Rowe, Dominic, Marder, Karen, Santiago, Anthony, Hu, Shu‐Ching, Isaacson, Stuart, Martinez, Javiar Ruiz, Tolosa, Eduardo, Tai, Yen, Politis, Marios, Smejdir, Debra, Rees, Linda, Williams, Karen, Kausar, Farah, Richardson, Whitney, Willeke, Diana, Peacock, Shawnees, Sommerfeld, Barbara, Freed, Alison, Wakeman, Katrina, Blair, Courtney, Guthrie, Stephanie, Harrell, Leigh, Hunter, Christine, Thomas, Cathi‐Ann, James, Raymond, Zimmerman, Grace, Brown, Victoria, and Mule, Jennifer

Subjects
Clinical and Health Psychology, Biomedical and Clinical Sciences, Neurosciences, Psychology, Human Genome, Parkinson's Disease, Neurodegenerative, Brain Disorders, Aging, Genetics, Neurological, Adult, Dementia, Disease Progression, Female, Genotype, Glucosylceramidase, Heterozygote, Humans, Male, Mental Status and Dementia Tests, Middle Aged, Mutation, Parkinson Disease, Phenotype, Parkinson’s Progression Markers Initiative, Clinical Sciences, Clinical and health psychology
Abstract

ObjectiveReduction in glucocerebrosidase (GCase; encoded by GBA) enzymatic activity has been linked to Parkinson's disease (PD). Here, we correlated GCase activity and PD phenotype in the Parkinson's Progression Markers Initiative (PPMI) cohort.MethodsWe measured GCase activity in dried blood spots from 1559 samples of participants in the inception PPMI cohort, collected in four annual visits (from baseline visit to Year-3). Participants (PD, n = 392; controls, n = 175) were fully sequenced for GBA variants by means of genome-wide genotyping arrays, whole-exome sequencing, whole-genome sequencing, Sanger sequencing, and RNA-sequencing.ResultsFifty-two PD participants (13.4%) and 13 (7.4%) controls carried a GBA variant. GBA status was strongly associated with GCase activity. Among noncarriers, GCase activity was similar between PD and controls. Among GBA p.E326K carriers (PD, n = 20; controls, n = 5), activity was significantly lower in PD carriers than control carriers (9.53 µmol/L/h vs. 11.68 µmol/L/h, P = 0.035). Glucocerebrosidase activity was moderately (r = 0.45) associated with white blood cell (WBC) count. Next, we divided the noncarriers with PD to tertiles based on WBC count-corrected enzymatic activity. Members of the lower tertile had higher MDS-Unified Parkinson's Disease Rating Scale motor score in the "off" medication examination at year-III exam. Longitudinal analyses demonstrated slight reduction of activity in samples collected earlier on in the study, likely because of longer storage time.InterpretationGCase activity is associated with GBA genotype, WBC count, and among p.E326K variant carriers, with PD status. Reduced activity may also be associated with worse phenotype but longer follow up is required to confirm this observation.

Published
2020

2. Clinical and dopamine transporter imaging characteristics of non-manifest LRRK2 and GBA mutation carriers in the Parkinson's Progression Markers Initiative (PPMI): a cross-sectional study

Author

Arnedo, Vanessa, Clark, Adrienne, Fraiser, Mark, Kopil, Catherine, Chowdhury, Sohini, Sherer, Todd, Daegele, Nichole, Casaceli, Cynthia, Dorsey, Ray, Wilson, Renee, Mahes, Sugi, Salerno, Christina, Crawford, Karen, Casalin, Paola, Malferrari, Giulia, Weisz, Mali Gani, Orr-Urtreger, Avi, Montine, Thomas, Baglieri, Chris, Christini, Amanda, Russell, David, Dahodwala, Nabila, Giladi, Nir, Factor, Stewart, Hogarth, Penelope, Standaert, David, Hauser, Robert, Jankovic, Joseph, Saint-Hilaire, Marie, Richard, Irene, Shprecher, David, Fernandez, Hubert, Brockmann, Katrina, Rosenthal, Liana, Barone, Paolo, Espay, Alberto, Rowe, Dominic, Marder, Karen, Santiago, Anthony, Hu, Shu-Ching, Isaacson, Stuart, Corvol, Jean-Christophe, Ruiz Martinez, Javiar, Tolosa, Eduardo, Tai, Yen, Politis, Marios, Smejdir, Debra, Rees, Linda, Williams, Karen, Kausar, Farah, Richardson, Whitney, Willeke, Diana, Peacock, Shawnees, Sommerfeld, Barbara, Freed, Alison, Wakeman, Katrina, Blair, Courtney, Guthrie, Stephanie, Harrell, Leigh, Hunter, Christine, Thomas, Cathi-Ann, James, Raymond, Zimmerman, Grace, Brown, Victoria, Mule, Jennifer, Hilt, Ella, Ribb, Kori, Ainscough, Susan, Wethington, Misty, Ranola, Madelaine, Mejia Santana, Helen, Moreno, Juliana, Raymond, Deborah, Speketer, Krista, Carvajal, Lisbeth, Carvalo, Stephanie, Croitoru, Ioana, Garrido, Alicia, Payne, Laura Marie, Viswanth, Veena, Severt, Lawrence, Facheris, Maurizio, Soares, Holly, Mintun, Mark A., Cedarbaum, Jesse, Taylor, Peggy, Biglan, Kevin, Vandenbroucke, Emily, Haider Sheikh, Zulfiqar, Bingol, Baris, Fischer, Tanya, Sardi, Pablo, Forrat, Remi, Reith, Alastair, Egebjerg, Jan, Ahlberg Hillert, Gabrielle, Saba, Barbara, Min, Chris, Umek, Robert, Mather, Joe, De Santi, Susan, Post, Anke, Boess, Frank, Taylor, Kirsten, Grachev, Igor, Avbersek, Andreja, Muglia, Pierandrea, Merchant, Kaplana, Tauscher, Johannes, Simuni, Tanya, Uribe, Liz, Cho, Hyunkeun Ryan, Caspell-Garcia, Chelsea, Coffey, Christopher S, Siderowf, Andrew, Trojanowski, John Q, Shaw, Leslie M, Seibyl, John, Singleton, Andrew, Toga, Arthur W, Galasko, Doug, Foroud, Tatiana, Tosun, Duygu, Poston, Kathleen, Weintraub, Daniel, Mollenhauer, Brit, Tanner, Caroline M, Kieburtz, Karl, Chahine, Lana M, Reimer, Alyssa, Hutten, Samantha J, Bressman, Susan, and Marek, Kenneth

Published
2020
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3. A Randomized Clinical Trial of High-Dosage Coenzyme Q10 in Early Parkinson Disease: No Evidence of Benefit

Author

Beal, M Flint, Oakes, David, Shoulson, Ira, Henchcliffe, Claire, Galpern, Wendy R, Haas, Richard, Juncos, Jorge L, Nutt, John G, Voss, Tiffini Smith, Ravina, Bernard, Shults, Clifford M, Helles, Karen, Snively, Victoria, Lew, Mark F, Griebner, Brian, Watts, Arthur, Gao, Shan, Pourcher, Emmanuelle, Bond, Louisette, Kompoliti, Katie, Agarwal, Pinky, Sia, Cherissa, Jog, Mandar, Cole, Linda, Sultana, Munira, Kurlan, Roger, Richard, Irene, Deeley, Cheryl, Waters, Cheryl H, Figueroa, Angel, Arkun, Ani, Brodsky, Matthew, Ondo, William G, Hunter, Christine B, Jimenez-Shahed, Joohi, Palao, Alicia, Miyasaki, Janis M, So, Julie, Tetrud, James, Reys, Liza, Smith, Katharine, Singer, Carlos, Blenke, Anita, Russell, David S, Cotto, Candace, Friedman, Joseph H, Lannon, Margaret, Zhang, Lin, Drasby, Edward, Kumar, Rajeev, Subramanian, Thyagarajan, Ford, Donna Stuppy, Grimes, David A, Cote, Diane, Conway, Jennifer, Siderowf, Andrew D, Evatt, Marian Leslie, Sommerfeld, Barbara, Lieberman, Abraham N, Okun, Michael S, Rodriguez, Ramon L, Merritt, Stacy, Swartz, Camille Louise, Martin, WR Wayne, King, Pamela, Stover, Natividad, Guthrie, Stephanie, Watts, Ray L, Ahmed, Anwar, Fernandez, Hubert H, Winters, Adrienna, Mari, Zoltan, Dawson, Ted M, Dunlop, Becky, Feigin, Andrew S, Shannon, Barbara, Nirenberg, Melissa Jill, Ogg, Mattson, Ellias, Samuel A, Thomas, Cathi-Ann, Frei, Karen, Bodis-Wollner, Ivan, Glazman, Sofya, Mayer, Thomas, Hauser, Robert A, Pahwa, Rajesh, Langhammer, April, Ranawaya, Ranjit, Derwent, Lorelei, Sethi, Kapil D, Farrow, Buff, Prakash, Rajan, Litvan, Irene, Robinson, Annette, Sahay, Alok, Gartner, Maureen, Hinson, Vanessa K, Markind, Samuel, Pelikan, Melisa, and Perlmutter, Joel S

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Parkinson's Disease, Prevention, Brain Disorders, Complementary and Integrative Health, Clinical Trials and Supportive Activities, Neurodegenerative, Clinical Research, Aging, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Neurological, Aged, Antioxidants, Dose-Response Relationship, Drug, Double-Blind Method, Early Diagnosis, Female, Humans, Male, Middle Aged, Parkinson Disease, Prospective Studies, Treatment Outcome, Ubiquinone, Parkinson Study Group QE3 Investigators, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

ImportanceCoenzyme Q10 (CoQ10), an antioxidant that supports mitochondrial function, has been shown in preclinical Parkinson disease (PD) models to reduce the loss of dopamine neurons, and was safe and well tolerated in early-phase human studies. A previous phase II study suggested possible clinical benefit.ObjectiveTo examine whether CoQ10 could slow disease progression in early PD.Design, setting, and participantsA phase III randomized, placebo-controlled, double-blind clinical trial at 67 North American sites consisting of participants 30 years of age or older who received a diagnosis of PD within 5 years and who had the following inclusion criteria: the presence of a rest tremor, bradykinesia, and rigidity; a modified Hoehn and Yahr stage of 2.5 or less; and no anticipated need for dopaminergic therapy within 3 months. Exclusion criteria included the use of any PD medication within 60 days, the use of any symptomatic PD medication for more than 90 days, atypical or drug-induced parkinsonism, a Unified Parkinson's Disease Rating Scale (UPDRS) rest tremor score of 3 or greater for any limb, a Mini-Mental State Examination score of 25 or less, a history of stroke, the use of certain supplements, and substantial recent exposure to CoQ10. Of 696 participants screened, 78 were found to be ineligible, and 18 declined participation.InterventionsThe remaining 600 participants were randomly assigned to receive placebo, 1200 mg/d of CoQ10, or 2400 mg/d of CoQ10; all participants received 1200 IU/d of vitamin E.Main outcomes and measuresParticipants were observed for 16 months or until a disability requiring dopaminergic treatment. The prospectively defined primary outcome measure was the change in total UPDRS score (Parts I-III) from baseline to final visit. The study was powered to detect a 3-point difference between an active treatment and placebo.ResultsThe baseline characteristics of the participants were well balanced, the mean age was 62.5 years, 66% of participants were male, and the mean baseline total UPDRS score was 22.7. A total of 267 participants required treatment (94 received placebo, 87 received 1200 mg/d of CoQ10, and 86 received 2400 mg/d of CoQ10), and 65 participants (29 who received placebo, 19 who received 1200 mg/d of CoQ10, and 17 who received 2400 mg/d of CoQ10) withdrew prematurely. Treatments were well tolerated with no safety concerns. The study was terminated after a prespecified futility criterion was reached. At study termination, both active treatment groups showed slight adverse trends relative to placebo. Adjusted mean changes (worsening) in total UPDRS scores from baseline to final visit were 6.9 points (placebo), 7.5 points (1200 mg/d of CoQ10; P = .49 relative to placebo), and 8.0 points (2400 mg/d of CoQ10; P = .21 relative to placebo).Conclusions and relevanceCoenzyme Q10 was safe and well tolerated in this population, but showed no evidence of clinical benefit.Trial registrationclinicaltrials.gov Identifier: NCT00740714.

Published
2014

4. A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit.

Author

Parkinson Study Group QE3 Investigators, Beal, M Flint, Oakes, David, Shoulson, Ira, Henchcliffe, Claire, Galpern, Wendy R, Haas, Richard, Juncos, Jorge L, Nutt, John G, Voss, Tiffini Smith, Ravina, Bernard, Shults, Clifford M, Helles, Karen, Snively, Victoria, Lew, Mark F, Griebner, Brian, Watts, Arthur, Gao, Shan, Pourcher, Emmanuelle, Bond, Louisette, Kompoliti, Katie, Agarwal, Pinky, Sia, Cherissa, Jog, Mandar, Cole, Linda, Sultana, Munira, Kurlan, Roger, Richard, Irene, Deeley, Cheryl, Waters, Cheryl H, Figueroa, Angel, Arkun, Ani, Brodsky, Matthew, Ondo, William G, Hunter, Christine B, Jimenez-Shahed, Joohi, Palao, Alicia, Miyasaki, Janis M, So, Julie, Tetrud, James, Reys, Liza, Smith, Katharine, Singer, Carlos, Blenke, Anita, Russell, David S, Cotto, Candace, Friedman, Joseph H, Lannon, Margaret, Zhang, Lin, Drasby, Edward, Kumar, Rajeev, Subramanian, Thyagarajan, Ford, Donna Stuppy, Grimes, David A, Cote, Diane, Conway, Jennifer, Siderowf, Andrew D, Evatt, Marian Leslie, Sommerfeld, Barbara, Lieberman, Abraham N, Okun, Michael S, Rodriguez, Ramon L, Merritt, Stacy, Swartz, Camille Louise, Martin, WR Wayne, King, Pamela, Stover, Natividad, Guthrie, Stephanie, Watts, Ray L, Ahmed, Anwar, Fernandez, Hubert H, Winters, Adrienna, Mari, Zoltan, Dawson, Ted M, Dunlop, Becky, Feigin, Andrew S, Shannon, Barbara, Nirenberg, Melissa Jill, Ogg, Mattson, Ellias, Samuel A, Thomas, Cathi-Ann, Frei, Karen, Bodis-Wollner, Ivan, Glazman, Sofya, Mayer, Thomas, Hauser, Robert A, Pahwa, Rajesh, Langhammer, April, Ranawaya, Ranjit, Derwent, Lorelei, Sethi, Kapil D, Farrow, Buff, Prakash, Rajan, Litvan, Irene, Robinson, Annette, Sahay, Alok, Gartner, Maureen, Hinson, Vanessa K, Markind, Samuel, and Pelikan, Melisa

Subjects
Parkinson Study Group QE3 Investigators, Humans, Parkinson Disease, Ubiquinone, Antioxidants, Early Diagnosis, Treatment Outcome, Prospective Studies, Double-Blind Method, Dose-Response Relationship, Drug, Aged, Middle Aged, Female, Male, Neurosciences, Brain Disorders, Aging, Neurodegenerative, Prevention, Clinical Research, Parkinson's Disease, Complementary and Integrative Health, Clinical Trials and Supportive Activities, 6.1 Pharmaceuticals, Neurological
Abstract

ImportanceCoenzyme Q10 (CoQ10), an antioxidant that supports mitochondrial function, has been shown in preclinical Parkinson disease (PD) models to reduce the loss of dopamine neurons, and was safe and well tolerated in early-phase human studies. A previous phase II study suggested possible clinical benefit.ObjectiveTo examine whether CoQ10 could slow disease progression in early PD.Design, setting, and participantsA phase III randomized, placebo-controlled, double-blind clinical trial at 67 North American sites consisting of participants 30 years of age or older who received a diagnosis of PD within 5 years and who had the following inclusion criteria: the presence of a rest tremor, bradykinesia, and rigidity; a modified Hoehn and Yahr stage of 2.5 or less; and no anticipated need for dopaminergic therapy within 3 months. Exclusion criteria included the use of any PD medication within 60 days, the use of any symptomatic PD medication for more than 90 days, atypical or drug-induced parkinsonism, a Unified Parkinson's Disease Rating Scale (UPDRS) rest tremor score of 3 or greater for any limb, a Mini-Mental State Examination score of 25 or less, a history of stroke, the use of certain supplements, and substantial recent exposure to CoQ10. Of 696 participants screened, 78 were found to be ineligible, and 18 declined participation.InterventionsThe remaining 600 participants were randomly assigned to receive placebo, 1200 mg/d of CoQ10, or 2400 mg/d of CoQ10; all participants received 1200 IU/d of vitamin E.Main outcomes and measuresParticipants were observed for 16 months or until a disability requiring dopaminergic treatment. The prospectively defined primary outcome measure was the change in total UPDRS score (Parts I-III) from baseline to final visit. The study was powered to detect a 3-point difference between an active treatment and placebo.ResultsThe baseline characteristics of the participants were well balanced, the mean age was 62.5 years, 66% of participants were male, and the mean baseline total UPDRS score was 22.7. A total of 267 participants required treatment (94 received placebo, 87 received 1200 mg/d of CoQ10, and 86 received 2400 mg/d of CoQ10), and 65 participants (29 who received placebo, 19 who received 1200 mg/d of CoQ10, and 17 who received 2400 mg/d of CoQ10) withdrew prematurely. Treatments were well tolerated with no safety concerns. The study was terminated after a prespecified futility criterion was reached. At study termination, both active treatment groups showed slight adverse trends relative to placebo. Adjusted mean changes (worsening) in total UPDRS scores from baseline to final visit were 6.9 points (placebo), 7.5 points (1200 mg/d of CoQ10; P = .49 relative to placebo), and 8.0 points (2400 mg/d of CoQ10; P = .21 relative to placebo).Conclusions and relevanceCoenzyme Q10 was safe and well tolerated in this population, but showed no evidence of clinical benefit.Trial registrationclinicaltrials.gov Identifier: NCT00740714.

Published
2014

5. 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

6. A Patient Registry to Identify Barriers to Health Care in an Underserved Parkinson’s Disease Population (P4-9.004)

Author

Bissonnette, Stephanie, primary, Owen, Rosemary, additional, Martin, Ashley, additional, Bird, Katelyn, additional, Stevenson, Michael, additional, James, Ray, additional, Lee, Rebekah, additional, Desrosier, Abigail, additional, Ellis, Theresa, additional, Wendel, Nicholas, additional, Bresler, Helen, additional, Lee, Bertha, additional, Thomas, Cathi Ann, additional, Saint-Hilaire, Marie-Helene, additional, and Shih, Ludy, additional

Published
2023
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8. Inosine to Increase Serum and Cerebrospinal Fluid Urate in Parkinson Disease: A Randomized Clinical Trial

Author

Schwarzschild, Michael A., Ascherio, Alberto, Beal, Flint M., Cudkowicz, Merit E., Curhan, Gary C., Hare, Joshua M., Hooper, Craig D., Kieburtz, Karl D., Macklin, Eric A., Oakes, David, Rudolph, Alice, Shoulson, Ira, Tennis, Marsha K., Espay, Alberto J., Gartner, Maureen, Hung, Albert, Bwala, Grace, Lenehan, Richard, Encarnacion, Elmyra, Ainslie, Melissa, Castillo, Richard, Togasaki, Daniel, Barles, Gina, Friedman, Joseph H., Niles, Lisa, Carter, Julie H., Murray, Megan, Goetz, Christopher G., Jaglin, Jeana, Ahmed, Anwar, Russell, David S., Cotto, Candace, Goudreau, John L., Russell, Doozie, Parashos, Sotirios Andreas, Ede, Patricia, Saint-Hilaire, Marie H., Thomas, Cathi-Ann, James, Raymond, Stacy, Mark A., Johnson, Julia, Gauger, Lisa, de Marcaida, Antonelle J., Thurlow, Sheila, Isaacson, Stuart H., Carvajal, Lisbeth, Rao, Jayaraman, Cook, Maureen, Hope-Porche, Charlise, McClurg, Lauren, Grasso, Daniela L., Logan, Robert, Orme, Constance, Ross, Tori, Brocht, Alicia F. D., Constantinescu, Radu, Sharma, Saloni, Venuto, Charles, Weber, Joseph, and Eaton, Ken

Published
2014
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9. 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

10. 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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11. Feasibility and safety of lumbar puncture in the Parkinson's disease research participants: Parkinson's Progression Marker Initiative (PPMI)

Author

Marek, Kenneth, Siderowf, Andrew, Seibyl, John, Coffey, Christopher, Tanner, Caroline, Tosun-Turgut, Duygu, Simuni, Tanya, Shaw, Leslie, Trojanowski, John, Singleton, Andrew, Kieburtz, Karl, Toga, Arthur, Mollenhauer, Brit, Galasko, Douglas, Poewe, Werner, Foroud, Tatiana, Poston, Kathleen, Sherer, Todd, Chowdhury, Sohini, Frasier, Mark, Kopil, Catherine, Arnedo, Vanessa, Daegele, Nichole, Casaceli, Cynthia, Dorsey, Ray, Wilson, Renee, Mahes, Sugi, Salerno, Christina, Caspell-Garcia, Chelsea, Crawford, Karen, Casalin, Paola, Malferrari, Giulia, Weisz, Mali Gani, Orr-Urtreger, Avi, Montine, Thomas, Russell, David, Dahodwala, Nabila, Giladi, Nir, Factor, Stewart, Hogarth, Penelope, Standaert, David, Hauser, Robert, Jankovic, Joseph, Saint-Hilaire, Marie, Richard, Irene, Shprecher, David, Fernandez, Hubert, Brockmann, Katrina, Rosenthal, Liana, Barone, Paolo, Espay, Alberto, Rowe, Dominic, Marder, Karen, Santiago, Anthony, Bressman, Susan, Hu, Shu-Ching, Isaacson, Stuart, Corvol, Jean-Christophe, Martinez, Javiar Ruiz, Tolosa, Eduardo, Tai, Yen, Politis, Marios, Smejdir, Debra, Rees, Linda, Williams, Karen, Kausar, Farah, Richardson, Whitney, Willeke, Diana, Peacock, Shawnees, Heim, Beatrice, Mirelman, Anat, Sommerfeld, Barbara, Freed, Alison, Wakeman, Katrina, Blair, Courtney, Guthrie, Stephanie, Harrell, Leigh, Hunter, Christine, Thomas, Cathi-Ann, James, Raymond, Zimmerman, Grace, Brown, Victoria, Mule, Jennifer, Hilt, Ella, Ribb, Kori, Ainscough, Susan, Wethington, Misty, Ranola, Madelaine, Santana, Helen Mejia, Moreno, Juliana, Raymond, Deborah, Speketer, Krista, Carvajal, Lisbeth, Carvalho, Stephanie, Croitoru, Ioana, Garrido, Alicia, Payne, Laura Marie, Viswanth, Veena, Severt, Lawrence, Facheris, Maurizio, Soares, Holly, Mintun, Mark A., Cedarbaum, Jesse, Taylor, Peggy, Biglan, Kevin, Vandenbroucke, Emily, Sheikh, Zulfiqar Haider, Bingol, Baris, Fischer, Tanya, Sardi, Pablo, Forrat, Remi, Reith, Alastair, Egebjerg, Jan, Hillert, Gabrielle Ahlberg, Saba, Barbara, Min, Chris, Umek, Robert, Mather, Joe, De Santi, Susan, Post, Anke, Boess, Frank, Taylor, Kirsten, Grachev, Igor, Avbersek, Andreja, Muglia, Pierandrea, Merchant, Kaplana, Tauscher, Johannes, Prakash, Neha, Tanner, Caroline M., Merchant, Kalpana, Chahine, Lana M., Weintraub, Daniel, Casaceli, Cindy, Herzog, Margaret, Marek, Ken, Frank, Samuel, and Jennings, Danna

Published
2019
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12. Clinical and dopamine transporter imaging characteristics of non-manifest LRRK2 and GBA mutation carriers in the Parkinson's Progression Markers Initiative (PPMI): a cross-sectional study

Author

Simuni, Tanya, primary, Uribe, Liz, additional, Cho, Hyunkeun Ryan, additional, Caspell-Garcia, Chelsea, additional, Coffey, Christopher S, additional, Siderowf, Andrew, additional, Trojanowski, John Q, additional, Shaw, Leslie M, additional, Seibyl, John, additional, Singleton, Andrew, additional, Toga, Arthur W, additional, Galasko, Doug, additional, Foroud, Tatiana, additional, Tosun, Duygu, additional, Poston, Kathleen, additional, Weintraub, Daniel, additional, Mollenhauer, Brit, additional, Tanner, Caroline M, additional, Kieburtz, Karl, additional, Chahine, Lana M, additional, Reimer, Alyssa, additional, Hutten, Samantha J, additional, Bressman, Susan, additional, Marek, Kenneth, additional, Arnedo, Vanessa, additional, Clark, Adrienne, additional, Fraiser, Mark, additional, Kopil, Catherine, additional, Chowdhury, Sohini, additional, Sherer, Todd, additional, Daegele, Nichole, additional, Casaceli, Cynthia, additional, Dorsey, Ray, additional, Wilson, Renee, additional, Mahes, Sugi, additional, Salerno, Christina, additional, Crawford, Karen, additional, Casalin, Paola, additional, Malferrari, Giulia, additional, Weisz, Mali Gani, additional, Orr-Urtreger, Avi, additional, Montine, Thomas, additional, Baglieri, Chris, additional, Christini, Amanda, additional, Russell, David, additional, Dahodwala, Nabila, additional, Giladi, Nir, additional, Factor, Stewart, additional, Hogarth, Penelope, additional, Standaert, David, additional, Hauser, Robert, additional, Jankovic, Joseph, additional, Saint-Hilaire, Marie, additional, Richard, Irene, additional, Shprecher, David, additional, Fernandez, Hubert, additional, Brockmann, Katrina, additional, Rosenthal, Liana, additional, Barone, Paolo, additional, Espay, Alberto, additional, Rowe, Dominic, additional, Marder, Karen, additional, Santiago, Anthony, additional, Hu, Shu-Ching, additional, Isaacson, Stuart, additional, Corvol, Jean-Christophe, additional, Ruiz Martinez, Javiar, additional, Tolosa, Eduardo, additional, Tai, Yen, additional, Politis, Marios, additional, Smejdir, Debra, additional, Rees, Linda, additional, Williams, Karen, additional, Kausar, Farah, additional, Richardson, Whitney, additional, Willeke, Diana, additional, Peacock, Shawnees, additional, Sommerfeld, Barbara, additional, Freed, Alison, additional, Wakeman, Katrina, additional, Blair, Courtney, additional, Guthrie, Stephanie, additional, Harrell, Leigh, additional, Hunter, Christine, additional, Thomas, Cathi-Ann, additional, James, Raymond, additional, Zimmerman, Grace, additional, Brown, Victoria, additional, Mule, Jennifer, additional, Hilt, Ella, additional, Ribb, Kori, additional, Ainscough, Susan, additional, Wethington, Misty, additional, Ranola, Madelaine, additional, Mejia Santana, Helen, additional, Moreno, Juliana, additional, Raymond, Deborah, additional, Speketer, Krista, additional, Carvajal, Lisbeth, additional, Carvalo, Stephanie, additional, Croitoru, Ioana, additional, Garrido, Alicia, additional, Payne, Laura Marie, additional, Viswanth, Veena, additional, Severt, Lawrence, additional, Facheris, Maurizio, additional, Soares, Holly, additional, Mintun, Mark A., additional, Cedarbaum, Jesse, additional, Taylor, Peggy, additional, Biglan, Kevin, additional, Vandenbroucke, Emily, additional, Haider Sheikh, Zulfiqar, additional, Bingol, Baris, additional, Fischer, Tanya, additional, Sardi, Pablo, additional, Forrat, Remi, additional, Reith, Alastair, additional, Egebjerg, Jan, additional, Ahlberg Hillert, Gabrielle, additional, Saba, Barbara, additional, Min, Chris, additional, Umek, Robert, additional, Mather, Joe, additional, De Santi, Susan, additional, Post, Anke, additional, Boess, Frank, additional, Taylor, Kirsten, additional, Grachev, Igor, additional, Avbersek, Andreja, additional, Muglia, Pierandrea, additional, Merchant, Kaplana, additional, and Tauscher, Johannes, additional

Published
2020
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13. Feasibility and safety of lumbar puncture in the Parkinson's disease research participants: Parkinson's Progression Marker Initiative (PPMI)

Author

Prakash, Neha, primary, Caspell-Garcia, Chelsea, additional, Coffey, Christopher, additional, Siderowf, Andrew, additional, Tanner, Caroline M., additional, Kieburtz, Karl, additional, Mollenhauer, Brit, additional, Galasko, Douglas, additional, Merchant, Kalpana, additional, Foroud, Tatiana, additional, Chahine, Lana M., additional, Weintraub, Daniel, additional, Casaceli, Cindy, additional, Dorsey, Ray, additional, Wilson, Renee, additional, Herzog, Margaret, additional, Daegele, Nichole, additional, Arnedo, Vanessa, additional, Frasier, Mark, additional, Sherer, Todd, additional, Marek, Ken, additional, Frank, Samuel, additional, Jennings, Danna, additional, Simuni, Tanya, additional, Marek, Kenneth, additional, Seibyl, John, additional, Tanner, Caroline, additional, Tosun-Turgut, Duygu, additional, Shaw, Leslie, additional, Trojanowski, John, additional, Singleton, Andrew, additional, Toga, Arthur, additional, Poewe, Werner, additional, Poston, Kathleen, additional, Chowdhury, Sohini, additional, Kopil, Catherine, additional, Casaceli, Cynthia, additional, Mahes, Sugi, additional, Salerno, Christina, additional, Crawford, Karen, additional, Casalin, Paola, additional, Malferrari, Giulia, additional, Weisz, Mali Gani, additional, Orr-Urtreger, Avi, additional, Montine, Thomas, additional, Russell, David, additional, Dahodwala, Nabila, additional, Giladi, Nir, additional, Factor, Stewart, additional, Hogarth, Penelope, additional, Standaert, David, additional, Hauser, Robert, additional, Jankovic, Joseph, additional, Saint-Hilaire, Marie, additional, Richard, Irene, additional, Shprecher, David, additional, Fernandez, Hubert, additional, Brockmann, Katrina, additional, Rosenthal, Liana, additional, Barone, Paolo, additional, Espay, Alberto, additional, Rowe, Dominic, additional, Marder, Karen, additional, Santiago, Anthony, additional, Bressman, Susan, additional, Hu, Shu-Ching, additional, Isaacson, Stuart, additional, Corvol, Jean-Christophe, additional, Martinez, Javiar Ruiz, additional, Tolosa, Eduardo, additional, Tai, Yen, additional, Politis, Marios, additional, Smejdir, Debra, additional, Rees, Linda, additional, Williams, Karen, additional, Kausar, Farah, additional, Richardson, Whitney, additional, Willeke, Diana, additional, Peacock, Shawnees, additional, Heim, Beatrice, additional, Mirelman, Anat, additional, Sommerfeld, Barbara, additional, Freed, Alison, additional, Wakeman, Katrina, additional, Blair, Courtney, additional, Guthrie, Stephanie, additional, Harrell, Leigh, additional, Hunter, Christine, additional, Thomas, Cathi-Ann, additional, James, Raymond, additional, Zimmerman, Grace, additional, Brown, Victoria, additional, Mule, Jennifer, additional, Hilt, Ella, additional, Ribb, Kori, additional, Ainscough, Susan, additional, Wethington, Misty, additional, Ranola, Madelaine, additional, Santana, Helen Mejia, additional, Moreno, Juliana, additional, Raymond, Deborah, additional, Speketer, Krista, additional, Carvajal, Lisbeth, additional, Carvalho, Stephanie, additional, Croitoru, Ioana, additional, Garrido, Alicia, additional, Payne, Laura Marie, additional, Viswanth, Veena, additional, Severt, Lawrence, additional, Facheris, Maurizio, additional, Soares, Holly, additional, Mintun, Mark A., additional, Cedarbaum, Jesse, additional, Taylor, Peggy, additional, Biglan, Kevin, additional, Vandenbroucke, Emily, additional, Sheikh, Zulfiqar Haider, additional, Bingol, Baris, additional, Fischer, Tanya, additional, Sardi, Pablo, additional, Forrat, Remi, additional, Reith, Alastair, additional, Egebjerg, Jan, additional, Hillert, Gabrielle Ahlberg, additional, Saba, Barbara, additional, Min, Chris, additional, Umek, Robert, additional, Mather, Joe, additional, De Santi, Susan, additional, Post, Anke, additional, Boess, Frank, additional, Taylor, Kirsten, additional, Grachev, Igor, additional, Avbersek, Andreja, additional, Muglia, Pierandrea, additional, Merchant, Kaplana, additional, and Tauscher, Johannes, additional

Published
2019
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14. 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., Marek, Kenneth, Jennings, Danna, Tanner, Caroline, Kieburtz, Karl, Poewe, Werner, Mollenhauer, Brit, Foroud, Tatiana, Galasko, Douglas, Sherer, Todd, Chowdhury, Sohini, Frasier, Mark, Kopil, Catherine, Arnedo, Vanessa, Rudolph, Alice, Seibyl, John, Mendick, Susan, Schuff, Norbert, Caspell, Chelsea, Uribe, Liz, Foster, Eric, Gloer, Katherine, Yankey, Jon, Toga, Arthur, Berlin, Dorit, Casalin, Paola, Malferrari, Giulia, Trojanowski, John, Shaw, Les, Russell, David, Factor, Stewart, Hogarth, Penelope, Standaert, David, Hauser, Robert, Jankovic, Joseph, Stern, Matthew, Chahine, Lama, Frank, Samuel, Seppi, Klaus, Shill, Holly, Berg, Daniela, Mari, Zoltan, Pavese, Nicola, Espay, Alberto, Devoto, Johnna, Rowe, Dominic, Brandabur, Melanie, Alcalay, Roy, Tolosa, Eduardo, York, Michele, Leary, Laura, Riordan, Cheryl, Rees, Linda, Portillo, Alicia, Lenahan, Art, Williams, Karen, Guthrie, Stephanie, Rawlins, Ashlee, Harlan, Sherry, Hunter, Christine, Tran, Baochan, Thomas, Cathi Ann, James, Raymond, Sprenger, Fabienne, Willeke, Diana, Obradov, Sanja, Mule, Jennifer, Gauss, Katharina, Fontaine, Deborah, Shah, Bina, Ranola, Madelaine, and Sims, John R.

Subjects
Adult, Male, Mild Cognitive Impairment, Anxiety, Apathy, Cognition, Depression, Impulse control disorder, Parkinson's disease, Psychosis, Aged, Aged, 80 and over, Biomarkers, Disruptive, Impulse Control, and Conduct Disorders, Female, Humans, Middle Aged, Prevalence, Psychotic Disorders, Cognition Disorders, Mental Disorders, Parkinson Disease, Severity of Illness Index, Neurology (clinical), Neurology, Disruptive, Impulse Control, Article, 80 and over, Cognitive Dysfunction, and Conduct Disorders
Abstract

This 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).Both 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.Parkinson'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.Baseline 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 0.001), with twice as many (14% vs. 7%) meeting criteria for clinically significant depressive symptoms. The PD patients also experienced more anxiety (P 0.001) and apathy (P 0.001) than HCs. Psychosis was uncommon in PD (3%), and no between-group difference was seen in ICD symptoms (P = 0.51).Approximately 10% of PD patients in the early, untreated disease state met traditional criteria of CI, which is a lower frequency compared with previous studies. Multiple dopaminergic-dependent NPS are also more common in these patients compared with the general population, but others associated with dopamine replacement therapy are not or are rare. Future analyses of this cohort will examine biological predictors and the course of CI and NPS. © 2015 International Parkinson and Movement Disorder Society.

Published
2015

15. 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

16. Correlates of excessive daytime sleepiness in de novo Parkinson's disease: A case control study

Author

Simuni, Tanya, Caspell Garcia, Chelsea, Coffey, Christopher, Chahine, Lama M., Lasch, Shirley, Oertel, Wolfgang H., Mayer, Geert, Högl, Birgit, Postuma, Ron, Videnovic, Aleksandar, Amara, Amy Willis, Marek, Ken, Russell, David, Factor, Stewart, Hogarth, Penelope, Standaert, David, Hauser, Robert, Jankovic, Joseph, Stern, Matthew, Chahine, Lama, Leverenz, James, Frank, Samuel, Richard, Irene, Seppi, Klaus, Shill, Holly, Fernandez, Hubert, Berg, Daniela, Wurster, Isabel, Galasko, Douglas, Mari, Zoltan, Brooks, David, Pavese, Nicola, Barone, Paolo, Isaacson, Stuart, Espay, Alberto, Rowe, Dominic, Brandabur, Melanie, Tetrud, James, Liang, Grace, Iranzo, Alex, Tolosa, Eduardo, Leary, Laura, Riordan, Cheryl, Rees, Linda, Portillo, Alicia, Lenahan, Art, Williams, Karen, Guthrie, Stephanie, Rawlins, Ashlee, Harlan, Sherry, Hunter, Christine, Tran, Baochan, Darin, Abigail, Linder, Carly, Baca, Marne, Venkov, Heli, Thomas, Cathi Ann, James, Raymond, Deeley, Cheryl, Bishop, Courtney, Sprenger, Fabienne, Willeke, Diana, Obradov, Sanja, Mule, Jennifer, Monahan, Nancy, Gauss, Katharina, Fontaine, Deborah, Gigliotti, Christina, Arita McCoy, Null, Dunlop, Becky, Shah, Bina, Ainscough, Susan, James, Angela, Silverstein, Rebecca, Espay, Kristy, Ranola, Madelaine, Trenkwalder, Claudia, Reith, Alastair D., Struyk, Arie, Boeve, Bradley, Harvey, Brian, Comella, Cindy, Tattersall, David, Kelly, Madeline, Foldvary, Nancy, Caspell, Chelsea, Uribe, Liz, Foster, Eric, Gloer, Katherine, Yankey, Jon, Kieburtz, Karl, Wilson, Renee, Rudolph, Alice, Casaceli, Cynthia, Todd Sherer, Null, Chowdhury, Sohini, Frasier, Mark, Kopil, Catherine, Arnedo, Vanessa, Schuff, Norbert, Casalin, Paola, Malferrari, Giulia, Trojanowski, John, Shaw, Les, Singleton, Andrew, and Hawkins, Keith A.

Subjects
Aged, 80 and over, Adult, Male, Daytime somnolence, Parkinson's disease, Parkinson Disease, Comorbidity, Disorders of Excessive Somnolence, Middle Aged, Article, Neurology, Case-Control Studies, Biomarkers, Aged, Female, Humans, Neurology (clinical), 80 and over
Abstract

This study was undertaken to determine the frequency and correlates of excessive daytime sleepiness in de novo, untreated Parkinson's disease (PD) patients compared with the matched healthy controls.Data were obtained from the Parkinson's Progression Markers Initiative, an international study of de novo, untreated PD patients and healthy controls. At baseline, participants were assessed with a wide range of motor and nonmotor scales, including the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Excessive daytime sleepiness was assessed based on the Epworth Sleepiness scale (ESS), with a cutoff of 10.Four hundred twenty-three PD subjects and 196 healthy controls were recruited into the study. Mean ESS (min, max) score was 5.8 (0, 20) for the PD subjects and 5.6 (0, 19) for healthy controls (P = 0.54). Sixty-six (15.6%) PD subjects and 24 (12%) healthy controls had ESS of at least 10 (P = 0.28). No difference was seen in demographic characteristics, age of onset, disease duration, PD subtype, cognitive status, or utilization of sedatives between the PD sleepiness-positive versus the negative group. The sleepiness-positive group had higher MDS-UPDRS Part I and II but not III scores, and higher depression and autonomic dysfunction scores. Sleepiness was associated with a marginal reduction of A-beta (P = 0.05) but not alpha-synuclein spinal fluid levels in PD.This largest case control study demonstrates no difference in prevalence of excessive sleepiness in subjects with de novo untreated PD compared with healthy controls. The only clinical correlates of sleepiness were mood and autonomic dysfunction. Ongoing longitudinal analyses will be essential to further examine clinical and biological correlates of sleepiness in PD and specifically the role of dopaminergic therapy.

Published
2015

17. Activity enhances dopaminergic long-duration response in Parkinson disease

Author

Jung Kang, Un, primary, Auinger, Peggy, additional, Fahn, Stanley, additional, Oakes, David, additional, Shoulson, Ira, additional, Kieburtz, Karl, additional, Rudolph, Alice, additional, Marek, Kenneth, additional, Seibyl, John, additional, Lang, Anthony, additional, Olanow, C. Warren, additional, Tanner, Caroline, additional, Schifitto, Giovanni, additional, Zhao, Hongwei, additional, Reyes, Lydia, additional, Shinaman, Aileen, additional, Comella, Cynthia L., additional, Goetz, Christopher, additional, Blasucci, Lucia M., additional, Samanta, Johan, additional, Stacy, Mark, additional, Williamson, Kelli, additional, Harrigan, Mary, additional, Greene, Paul, additional, Ford, Blair, additional, Moskowitz, Carol, additional, Truong, Daniel D., additional, Pathak, Mayank, additional, Jankovic, Joseph, additional, Ondo, William, additional, Atassi, Farah, additional, Hunter, Christine, additional, Jacques, Carol, additional, Friedman, Joseph H., additional, Lannon, Margaret, additional, Russell, David S., additional, Jennings, Danna, additional, Fussell, Barbara, additional, Standaert, David, additional, Schwarzschild, Michael A., additional, Growdon, John H., additional, Tennis, Marsha, additional, Gauthier, Serge, additional, Panisset, Michel, additional, Hall, Jean, additional, Gancher, Stephen, additional, Hammerstad, John P., additional, Stone, Claudia, additional, Alexander-Brown, Barbara, additional, Factor, Stewart A., additional, Molho, Eric, additional, Brown, Diane, additional, Evans, Sharon, additional, Clark, Jeffrey, additional, Manyam, Bala, additional, Simpson, Patricia, additional, Wulbrecht, Brian, additional, Whetteckey, Jacqueline, additional, Martin, Wayne, additional, Roberts, Ted, additional, King, Pamela, additional, Hauser, Robert, additional, Zesiewicz, Theresa, additional, Gauger, Lisa, additional, Trugman, Joel, additional, Wooten, G. Frederick, additional, Rost-Ruffner, Elke, additional, Perlmutter, Joel, additional, Racette, Brad A., additional, Suchowersky, Oksana, additional, Ranawaya, Ranjit, additional, Wood, Susan, additional, Pantella, Carol, additional, Kurlan, Roger, additional, Richard, Irene, additional, Pearson, Nancy, additional, Caviness, John N., additional, Adler, Charles, additional, Lind, Marlene, additional, Simuni, Tanya, additional, Siderowf, Andrew, additional, Colcher, Amy, additional, Lloyd, Mary, additional, Weiner, William, additional, Shulman, Lisa, additional, Koller, William, additional, Lyons, Kelly, additional, Feldman, Robert G., additional, Saint-Hilaire, Marie H., additional, Ellias, Samuel, additional, Thomas, Cathi-Ann, additional, Juncos, Jorge, additional, Watts, Ray, additional, Partlow, Anna, additional, Tetrud, James, additional, Togasaki, Daniel M., additional, Stewart, Tracy, additional, Mark, Margery H., additional, Sage, Jacob I., additional, Caputo, Debbie, additional, Gould, Harry, additional, Rao, Jayaraman, additional, McKendrick, Ann, additional, Brin, Mitchell, additional, Danisi, Fabio, additional, Benabou, Reina, additional, Hubble, Jean, additional, Paulson, George W., additional, Reider, Carson, additional, Birnbaum, Alex, additional, Miyasaki, Janis, additional, Johnston, Lisa, additional, So, Julie, additional, Pahwa, Rajesh, additional, Dubinsky, Richard M., additional, Wszolek, Zbigniew, additional, Uitti, Ryan, additional, Turk, Margaret, additional, Tuite, Paul, additional, Rottenberg, David, additional, Hansen, Joy, additional, Ramos, Serrano, additional, Waters, Cheryl, additional, Lew, Mark, additional, Welsh, Mickie, additional, Kawai, Connie, additional, O'Brien, Christopher, additional, Kumar, Rajeev, additional, Seeberger, Lauren, additional, Judd, Deborah, additional, Mendis, Tilak, additional, Barclay, C. Lynn, additional, Grimes, David A., additional, Sutherland, Laura, additional, Dawson, Ted, additional, Reich, Stephen, additional, Dunlop, Rebecca, additional, Albin, Roger, additional, Frey, Kirk, additional, and Wernette, Kristine, additional

Published
2012
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