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1. High ultrasensitive serum C-reactive protein may be related to freezing of gait in Parkinson's disease patients

Author

Santos-Garcia, D, Fonticoba, TD, Castro, ES, Diaz, AA, Gonzalez, JMP, Panceiras, MJF, Sancho, CG, Jesus, S, Mir, P, Aguilar, M, Pastor, P, Vara, JH, de Fabregues-Boixar, O, Puente, V, Cuevas, AC, Gonzalez-Aramburu, I, Infante, J, Padilla, FC, Pueyo, M, Escalante, S, Bernardo, N, Solano, B, Foraster, AC, Martinez-Martin, P, Astrid, DA, Almeria, M, Losada, MGA, Canovas, AA, Frech, FA, Sauco, MA, Arnaiz, S, Arribas, S, Vidondo, AA, Avila, MA, Bejr-Kasem, H, Estrada, MB, Boti, M, Borrue, C, Gonzalez, CC, Lopez, IC, Caballol, N, Lorenzo, AC, Carrillo, F, Casas, E, Catalan, MJ, Clavero, P, Fernandez, AC, Cubo, E, Diez-Fairen, M, Erro, E, Peyret, EE, Guillan, NF, Gamez, P, Gallego, M, Caldentey, JG, Campos, CG, Moreno, JMG, Gaston, I, Garre, MPG, Aloy, JG, Ardura, JG, Garcia, BG, Palmas, MJG, Toledo, GRG, Diaz, AG, Sola, MG, Guardia, G, Horta-Barba, A, Kulisevsky, J, Kurtis, M, Labandeira, C, Labrador, MA, Lacruz, F, Castro, ML, Legarda, I, Ariztegui, NL, Diaz, LML, Manzanares, LL, Seoane, BL, Macias, Y, Mata, M, Andres, GM, Marti, MJ, Castrillo, JCM, McAfee, D, Meitin, MT, Gonzalez, MM, del Barrio, CM, Santiago, JM, Casado, MIM, Dieguez, AM, Nogueira, V, Amado, AN, Ponte, SN, Ordas, C, Pagonabarraga, J, Parees, I, Pascual-Sedano, B, Fuertes, AP, Noguera, RP, Planellas, L, Prats, MA, Jurczynska, CP, Rafales, NR, Mendez, LR, Perez, ABR, Roldan, F, De Arcos, MR, Martinez, JR, Alonso, PS, Sanchez-Carpintero, M, Diez, GS, Rodriguez, AS, Santacruz, P, Rodriguez, JCS, Seijo, M, Serarols, A, Pena, MS, Tartari, JP, Valero, C, Vargas, L, Gomez, RV, Vela, L, Villanueva, C, Vives, B, and Villar, MD

Subjects
Inflammation, genetic structures, Parkinson's disease, Freezing, C-Reactive protein, Gait
Abstract

C-reactive protein (CRP) is a biomarker of systemic inflammation that has been linked to accelerated decline in walking speed in older adults. The aim of the present study was to compare the CRP levels of PD patients with vs patients without freezing of gait (FOG). Patients and controls participating in the COPPADIS-2015 study that performed blood extraction for determining molecular serum biomarkers were included. Patients with FOG were identified as those with a score of 1 or greater on item-3 of the Freezing of Gait Questionnaire (FOG-Q). Immunoassay was used for determining ultrasensitive CRP (US-CRP) level (mg/dL). In the PD group (n = 225; 61.8 +/- 9.5 years old, 61.8% males), 32% of the patients presented FOG but none in the control group (n = 65; 60.3 +/- 6.1 years old, 56.9% males) (p < 0.0001). Differences in US-CRP level were significant in patients with FOG vs patients without FOG and vs controls (0.31 +/- 0.52 vs 0.16 +/- 0.21 vs 0.21 +/- 0.22; p = 0.04). Significant differences were also observed between patients with vs without FOG (p = 0.001) but not between patients and controls (p = 0.163). US-CRP level was related to FOG (OR = 4.369; 95% CI 1.105-17.275; p = 0.036) along with H&Y (OR = 2.974; 95% CI 1.113-7.943; p = 0.030) and non-motor symptoms burden (NMSS total score; OR = 1.017; 95% CI 1.005-1.029; p = 0.006) after adjusting for age, gender, disease duration, equivalent daily levodopa dose, number of non-antiparkinsonian drugs per day, motor fluctuations, cognition, motor phenotype, and chronic use of anti-inflammatory drugs. The present study suggests that serum US-CRP level is related to FOG in PD patients. Inflammation could be linked to FOG development.

Published
2019

2. COPPADIS-2015 (COhort of Patients with PArkinson's DIsease in Spain, 2015): an ongoing global Parkinson's disease project about disease progression with more than 1000 subjects included. Results from the baseline evaluation

Author

Garcia, DS, Jesus, S, Aguilar, M, Planellas, LL, Caldentey, JG, Caballol, N, Legarda, I, Vara, JH, Cabo, I, Manzanares, LL, Aramburu, IG, Rivera, MAA, Catalan, MJ, Diaz, LL, Puente, V, Moreno, JMG, Borrue, C, Vila, BS, Sauco, MA, Vela, L, Escalante, S, Cubo, E, Padilla, FC, Castrillo, JCM, Alonso, PS, Losada, MGA, Ariztegui, NL, Gaston, I, Kulisevsky, J, Gonzalez, MM, Seijo, M, Martinez, JR, Valero, C, Kurtis, M, de Fabregues-Boixar, O, Ardura, JG, Jurczynska, CP, Martinez-Martin, P, Mir, P, Astrid, DA, Almeria, M, Canovas, AA, Frech, FA, Diaz, AA, Arnaiz, S, Arribas, S, Vidondo, AA, Lambrich, NB, Bejr-Kasem, H, Estrada, MB, Boti, M, Gonzalez, CC, Lorenzo, AC, Carrillo, F, Casas, E, Clavero, P, Fernandez, AC, Foraster, AC, Cuevas, AC, Fonticoba, TD, Diez-Fairen, M, Erro, E, Peyret, EE, Guillan, NF, Gamez, P, Gallego, M, Campos, CG, Garre, MPG, Aloy, JG, Garcia, BG, Palmas, MJG, Toledo, GRG, Diaz, AG, Sola, MG, Guardia, G, Horta-Barba, A, Infante, J, Labandeira, C, Labrador, MA, Lacruz, F, Castro, ML, Seoane, BL, Macias, Y, Mata, M, Andres, GM, Marti, MJ, McAfee, D, Meitin, MT, del Barrio, CM, Santiago, JM, Casado, MIM, Dieguez, AM, Nogueira, V, Amado, AN, Ponte, SN, Ordas, C, Pagonabarraga, J, Parees, I, Pascual-Sedano, B, Pastor, P, Fuertes, AP, Noguera, RP, Prats, MA, Morlans, MP, Rafales, NR, Mendez, LR, Perez, ABR, Roldan, F, De Arcos, MR, Sanchez-Carpintero, M, Diez, GS, Rodriguez, AS, Santacruz, P, Rodriguez, JCS, Serarols, A, Pena, MS, Castro, ES, Tartari, JP, Vargas, L, Gomez, RV, Villanueva, C, Vives, B, and Villar, MD

Subjects
motor fluctuations, quality of life, mood, Parkinson's disease, gait, non-motor symptoms
Abstract

Background and purpose In Parkinson's disease (PD), the course of the disorder is highly variable between patients. Well-designed, prospective studies for identifying PD progression biomarkers are necessary. Our aim was to show the results of baseline evaluations of an ongoing global PD project, COPPADIS-2015 (Cohort of Patients with PArkinson's DIsease in Spain, 2015). Methods This was an observational, descriptive, nationwide study (Spain). The recruitment period ended in October 2017. Baseline evaluation included more than 15 validated scales and complementary studies in a subgroup of participants. Results In total, 1174 subjects from 35 centres were considered valid for baseline analysis: 694 patients (62.6 +/- 8.9 years old, 60.3% males), 273 caregivers (58.5 +/- 11.9 years old, 31.8% males) and 207 controls (61 +/- 8.3 years old, 49.5% males). The mean disease duration was 5.5 +/- 4.4 years. Hoehn and Yahr stage was 1 or 2 in 90.7% of the patients whilst 33.9% and 18.1% of them presented motor fluctuations and dyskinesias, respectively. The mean Non-Motor Symptoms Scale total score was 45.4 +/- 38.1, and 30.4% of the patients presented cognitive impairment, 16.1% major depression, 12.7% impulse control disorder, 7.2% compulsive behaviour, 57.2% pain and 13.2% falls. Compared to the control group, PD patients presented a significantly higher burden of non-motor symptoms and a worse quality of life. More than 300 subjects conducted complementary studies (serum biomarkers, genetic and neuroimaging). Conclusions Parkinson's disease is a complex disorder and different non-motor symptoms are frequently present and are more prevalent than in controls. In real clinical practice it is important to ask for them.

Published
2019

3. Increased homocysteine levels correlate with cortical structural damage in Parkinson's disease.

Author

Sampedro F, Martínez-Horta S, Horta-Barba A, Grothe MJ, Labrador-Espinosa MA, Jesús S, Adarmes-Gómez A, Carrillo F, Puig-Davi A, Lora FR, Barberá MA, Pastor P, Arroyo SE, Vila BS, Foraster AC, Martínez JR, Padilla FC, Morlans MP, Aramburu IG, Ceberio JI, Vara JH, de Fábregues-Boixar O, de Deus Fonticoba T, Ávila A, Martínez-Castrillo JC, Bejr-Kasem H, Campolongo A, Pascual-Sedano B, Martínez-Martín P, Santos-García D, Mir P, and Kulisevsky J

Subjects
Cerebral Cortex diagnostic imaging, Cerebral Cortex pathology, Cerebral Cortical Thinning, Homocysteine, Humans, Magnetic Resonance Imaging, Parkinson Disease complications
Abstract

Background: Blood homocysteine appears to be increased in Parkinson's disease (PD) and may play a role in the development and progression of this disorder. However, the specific contribution of abnormal homocysteine levels to cortical degeneration in PD remains elusive., Objective: To characterize the cortical structural correlates of homocysteine levels in PD., Methods: From the COPPADIS cohort, we identified a subset of PD patients and healthy controls (HC) with available homocysteine and imaging data. Surface-based vertex-wise multiple regression analyses were performed to investigate the cortical macrostructural (cortical thinning) and microstructural (increased intracortical diffusivity) correlates of homocysteine levels in this sample., Results: A total of 137 PD patients and 43 HC were included. Homocysteine levels were increased in the PD group (t = -2.2, p = 0.03), correlating in turn with cognitive performance (r = -0.2, p = 0.03). Homocysteine in PD was also associated with frontal cortical thinning and, in a subset of patients with available DTI data, with microstructural damage in frontal and posterior-cortical regions (p < 0.05 Monte-Carlo corrected)., Conclusions: Homocysteine in PD appears to be associated with cognitive performance and structural damage in the cerebral cortex. These findings not only reinforce the presence and importance of cortical degeneration in PD, but also suggest that homocysteine plays a role among the multiple pathological processes thought to be involved in its development., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Published
2022
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4. In vivo cholinergic basal forebrain degeneration and cognition in Parkinson's disease: Imaging results from the COPPADIS study.

Author

Grothe MJ, Labrador-Espinosa MA, Jesús S, Macías-García D, Adarmes-Gómez A, Carrillo F, Camacho EI, Franco-Rosado P, Lora FR, Martín-Rodríguez JF, Barberá MA, Pastor P, Arroyo SE, Vila BS, Foraster AC, Martínez JR, Padilla FC, Morlans MP, Aramburu IG, Ceberio JI, Vara JH, de Fábregues-Boixar O, de Deus Fonticoba T, Pascual-Sedano B, Kulisevsky J, Martínez-Martín P, Santos-García D, and Mir P

Subjects
Aged, Basal Forebrain diagnostic imaging, Cognitive Dysfunction etiology, Cohort Studies, Diffusion Tensor Imaging, Female, Hippocampus diagnostic imaging, Humans, Male, Middle Aged, Multimodal Imaging, Neuroimaging, Neuropsychological Tests, Parkinson Disease complications, Parkinson Disease diagnostic imaging, Basal Forebrain pathology, Cognitive Dysfunction physiopathology, Hippocampus pathology, Magnetic Resonance Imaging, Parkinson Disease pathology, Parkinson Disease physiopathology
Abstract

Introduction: We aimed to assess associations between multimodal neuroimaging measures of cholinergic basal forebrain (CBF) integrity and cognition in Parkinson's disease (PD) without dementia., Methods: The study included a total of 180 non-demented PD patients and 45 healthy controls, who underwent structural MRI acquisitions and standardized neurocognitive assessment through the PD-Cognitive Rating Scale (PD-CRS) within the multicentric COPPADIS-2015 study. A subset of 73 patients also had Diffusion Tensor Imaging (DTI) acquisitions. Volumetric and microstructural (mean diffusivity, MD) indices of CBF degeneration were automatically extracted using a stereotactic CBF atlas. For comparison, we also assessed multimodal indices of hippocampal degeneration. Associations between imaging measures and cognitive performance were assessed using linear models., Results: Compared to controls, CBF volume was not significantly reduced in PD patients as a group. However, across PD patients lower CBF volume was significantly associated with lower global cognition (PD-CRS total : r = 0.37, p < 0.001), and this association remained significant after controlling for several potential confounding variables (p = 0.004). Analysis of individual item scores showed that this association spanned executive and memory domains. No analogue cognition associations were observed for CBF MD. In covariate-controlled models, hippocampal volume was not associated with cognition in PD, but there was a significant association for hippocampal MD (p = 0.02)., Conclusions: Early cognitive deficits in PD without dementia are more closely related to structural MRI measures of CBF degeneration than hippocampal degeneration. In our multicentric imaging acquisitions, DTI-based diffusion measures in the CBF were inferior to standard volumetric assessments for capturing cognition-relevant changes in non-demented PD., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Published
2021
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