Skip to main content
Top
Published in: Journal of Neural Transmission 12/2019

01-12-2019 | Parkinson's Disease | Neurology and Preclinical Neurological Studies - Original Article

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

Authors: Diego Santos-García, T. de Deus Fonticoba, E. Suárez Castro, A. Aneiros Díaz, J. M. Paz González, M. J. Feal Panceiras, C. García Sancho, S. Jesús, P. Mir, M. Aguilar, P. Pastor, J. Hernández Vara, O. de Fábregues-Boixar, V. Puente, A. Crespo Cuevas, I. González-Aramburu, J. Infante, F. Carrillo Padilla, M. Pueyo, S. Escalante, N. Bernardo, B. Solano, A. Cots Foraster, P. Martinez-Martin, on behalf of the COPPADIS Study Group

Published in: Journal of Neural Transmission | Issue 12/2019

Login to get access

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.
Appendix
Available only for authorised users
Literature
go back to reference Amboni M, Stocchi F, Abbruzzese G, DEEP Study Group et al (2015) Prevalence and associated features of self-reported freezing of gait in Parkinson disease: the DEEP FOG study. Parkinsonism Relat Disord 21:644–649CrossRef Amboni M, Stocchi F, Abbruzzese G, DEEP Study Group et al (2015) Prevalence and associated features of self-reported freezing of gait in Parkinson disease: the DEEP FOG study. Parkinsonism Relat Disord 21:644–649CrossRef
go back to reference Anand SS, Yusuf S (2010) C-reactive protein is a bystander of cardiovascular disease. Eur Heart J 31:2092–2096CrossRef Anand SS, Yusuf S (2010) C-reactive protein is a bystander of cardiovascular disease. Eur Heart J 31:2092–2096CrossRef
go back to reference Brinkley TE, Leng X, Miller ME, Kitzman DW, Pahor M, Berry MJ et al (2009) Chronic inflammation is associated with low physical function in older adults across multiple comorbidities. J Gerontol A Biol Sci Med Sci 64:455–461CrossRef Brinkley TE, Leng X, Miller ME, Kitzman DW, Pahor M, Berry MJ et al (2009) Chronic inflammation is associated with low physical function in older adults across multiple comorbidities. J Gerontol A Biol Sci Med Sci 64:455–461CrossRef
go back to reference Bruunsgaard H (2005) Physical activity and modulation of systemic low-level inflammation. J Leukoc Biol 78:819–835CrossRef Bruunsgaard H (2005) Physical activity and modulation of systemic low-level inflammation. J Leukoc Biol 78:819–835CrossRef
go back to reference Carvalho DZ, Schönwald SV, Schumacher-Schuh AF et al (2015) Overnight S100B in Parkinson’s disease: a glimpse into sleep-related neuroinflammation. Neurosci Lett 608:57–63CrossRef Carvalho DZ, Schönwald SV, Schumacher-Schuh AF et al (2015) Overnight S100B in Parkinson’s disease: a glimpse into sleep-related neuroinflammation. Neurosci Lett 608:57–63CrossRef
go back to reference Cesari M, Penninx BW, Pahor M et al (2004) Inflammatory markers and physical performance in older persons: the InCHIANTI study. J Gerontol A Biol Sci Med Sci 59:242–248CrossRef Cesari M, Penninx BW, Pahor M et al (2004) Inflammatory markers and physical performance in older persons: the InCHIANTI study. J Gerontol A Biol Sci Med Sci 59:242–248CrossRef
go back to reference Christine CW, Auinger P, Joslin A, Yelpaala Y, Green R, Parkinson Study Group-DATATOP Investigators (2018) Vitamin B12 and homocysteine levels predict different outcomes in early Parkinson’s disease. Mov Disord 33:762–770CrossRef Christine CW, Auinger P, Joslin A, Yelpaala Y, Green R, Parkinson Study Group-DATATOP Investigators (2018) Vitamin B12 and homocysteine levels predict different outcomes in early Parkinson’s disease. Mov Disord 33:762–770CrossRef
go back to reference de Farias CC, Maes M, Bonifacio KL et al (2016) Highly specific changes in antioxidant levels and lipid peroxidation in Parkinson’s disease and its progression: disease and staging biomarkers and new drug targets. Neurosci Lett 617:66–71CrossRef de Farias CC, Maes M, Bonifacio KL et al (2016) Highly specific changes in antioxidant levels and lipid peroxidation in Parkinson’s disease and its progression: disease and staging biomarkers and new drug targets. Neurosci Lett 617:66–71CrossRef
go back to reference Fasano A, Herman T, Tessitore A, Strafella AP, Bohnen NI (2015) Neuroimaging of freezing of gait. J Parkinsons Dis 5:241–254CrossRef Fasano A, Herman T, Tessitore A, Strafella AP, Bohnen NI (2015) Neuroimaging of freezing of gait. J Parkinsons Dis 5:241–254CrossRef
go back to reference Hassin-Baer S, Cohen OS, Vakil E et al (2011) Is C-reactive protein level a marker of advanced motor and neuropsychiatric complications in Parkinson’s disease? J Neural Transm 118:539–543CrossRef Hassin-Baer S, Cohen OS, Vakil E et al (2011) Is C-reactive protein level a marker of advanced motor and neuropsychiatric complications in Parkinson’s disease? J Neural Transm 118:539–543CrossRef
go back to reference Iansek R, Danoudis M (2016) Freezing of gait in Parkinson’s disease: its pathophysiology and pragmatic approaches to management. Mov Disord Clin Pract 4:290–297CrossRef Iansek R, Danoudis M (2016) Freezing of gait in Parkinson’s disease: its pathophysiology and pragmatic approaches to management. Mov Disord Clin Pract 4:290–297CrossRef
go back to reference Juma WM, Lira A, Marzuk A, Marzuk Z, Hakim AM, Thompson CS (2011) C-reactive protein expression in a rodent model of chronic cerebral hypoperfusion. Brain Res 1414:85–93CrossRef Juma WM, Lira A, Marzuk A, Marzuk Z, Hakim AM, Thompson CS (2011) C-reactive protein expression in a rodent model of chronic cerebral hypoperfusion. Brain Res 1414:85–93CrossRef
go back to reference Kositsawat J, Barry LC, Kuchel GA (2013) C-reactive protein, vitamin D deficiency, and slow gait speed. J Am Geriatr Soc 61:1574–1579CrossRef Kositsawat J, Barry LC, Kuchel GA (2013) C-reactive protein, vitamin D deficiency, and slow gait speed. J Am Geriatr Soc 61:1574–1579CrossRef
go back to reference Levin J, Bötzel K, Giese A, Vogeser M, Lorenzl S (2010) Elevated levels of methylmalonate and homocysteine in Parkinson’s disease, progressive supranuclear palsy and amyotrophic lateral sclerosis. Dement Geriatr Cogn Disord 29:553–559CrossRef Levin J, Bötzel K, Giese A, Vogeser M, Lorenzl S (2010) Elevated levels of methylmalonate and homocysteine in Parkinson’s disease, progressive supranuclear palsy and amyotrophic lateral sclerosis. Dement Geriatr Cogn Disord 29:553–559CrossRef
go back to reference Lindqvist D, Hall S, Surova Y et al (2013) Cerebrospinal fluid inflammatory markers in Parkinson’s disease—associations with depression, fatigue, and cognitive impairment. Brain Behav Immun 33:183–189CrossRef Lindqvist D, Hall S, Surova Y et al (2013) Cerebrospinal fluid inflammatory markers in Parkinson’s disease—associations with depression, fatigue, and cognitive impairment. Brain Behav Immun 33:183–189CrossRef
go back to reference Mancini M, Bloem BR, Horak FB et al (2019) Clinical and methodological challenges for assessing freezing of gait: future perspectives. Mov Disord (epub ahead of print) Mancini M, Bloem BR, Horak FB et al (2019) Clinical and methodological challenges for assessing freezing of gait: future perspectives. Mov Disord (epub ahead of print)
go back to reference Perez-Lloret S, Negre-Pages L, Damier P et al (2014) Prevalence, determinants, and effect on quality of life of freezing of gait in Parkinson disease. JAMA Neurol 71:884–890CrossRef Perez-Lloret S, Negre-Pages L, Damier P et al (2014) Prevalence, determinants, and effect on quality of life of freezing of gait in Parkinson disease. JAMA Neurol 71:884–890CrossRef
go back to reference Perry VH (2004) The influence of systemic inflammation on inflammation in the brain: implications for chronic neurodegenerative disease. Brain Behav Immun 18:407–413CrossRef Perry VH (2004) The influence of systemic inflammation on inflammation in the brain: implications for chronic neurodegenerative disease. Brain Behav Immun 18:407–413CrossRef
go back to reference Qiu X, Xiao Y, Wu J, Gan L, Huang Y, Wang J (2019) C-reactive protein and risk of parkinson’s disease: a systematic review and meta-analysis. Front Neurol 10:384CrossRef Qiu X, Xiao Y, Wu J, Gan L, Huang Y, Wang J (2019) C-reactive protein and risk of parkinson’s disease: a systematic review and meta-analysis. Front Neurol 10:384CrossRef
go back to reference Rees K, Stowe R, Patel S et al (2011) Non-steroidal anti-inflammatory drugs as disease-modifying agents for Parkinson’s disease: evidence from observational studies. Cochrane Database Syst Rev 9:11 Rees K, Stowe R, Patel S et al (2011) Non-steroidal anti-inflammatory drugs as disease-modifying agents for Parkinson’s disease: evidence from observational studies. Cochrane Database Syst Rev 9:11
go back to reference Sanjari Moghaddam H, Valitabar Z, Ashraf-Ganjouei A, Mojtahed Zadeh M, Ghazi Sherbaf F, Aarabi MH (2018) Cerebrospinal fluid C-reactive protein in Parkinson’s disease: associations with motor and non-motor symptoms. Neuromol Med 20:376–385CrossRef Sanjari Moghaddam H, Valitabar Z, Ashraf-Ganjouei A, Mojtahed Zadeh M, Ghazi Sherbaf F, Aarabi MH (2018) Cerebrospinal fluid C-reactive protein in Parkinson’s disease: associations with motor and non-motor symptoms. Neuromol Med 20:376–385CrossRef
go back to reference Santos García D, Jesús S, Aguilar M, Planellas LL, García Caldentey J, Caballol N, Legarda I, Hernández Vara J, Cabo I, López Manzanares L, González Aramburu I, Ávila Rivera MA, Catalán MJ, López Díaz L, Puente V, García Moreno JM, Borrué C, Solano Vila B, Álvarez Sauco M, Vela L, Escalante S, Cubo E, Carrillo Padilla F, Martínez Castrillo JC, Sánchez Alonso P, Alonso Losada MG, López Ariztegui N, Gastón I, Kulisevsky J, Menéndez González M, Seijo M, Rúiz Martínez J, Valero C, Kurtis M, de Fábregues-Boixar O, González Ardura J, Prieto Jurczynska C, Martinez-Martin P, Mir P; COPPADIS Study Group (2019) COPPADIS-2015 (COhort of Patient’s with PArkinson’s DIsease in Spain, 2015) An ongoing global Parkinson’s disease Project about disease progression with more than 1,000 subjects included. Results from the baseline evaluation. Eur J Neurol 66:151–158 Santos García D, Jesús S, Aguilar M, Planellas LL, García Caldentey J, Caballol N, Legarda I, Hernández Vara J, Cabo I, López Manzanares L, González Aramburu I, Ávila Rivera MA, Catalán MJ, López Díaz L, Puente V, García Moreno JM, Borrué C, Solano Vila B, Álvarez Sauco M, Vela L, Escalante S, Cubo E, Carrillo Padilla F, Martínez Castrillo JC, Sánchez Alonso P, Alonso Losada MG, López Ariztegui N, Gastón I, Kulisevsky J, Menéndez González M, Seijo M, Rúiz Martínez J, Valero C, Kurtis M, de Fábregues-Boixar O, González Ardura J, Prieto Jurczynska C, Martinez-Martin P, Mir P; COPPADIS Study Group (2019) COPPADIS-2015 (COhort of Patient’s with PArkinson’s DIsease in Spain, 2015) An ongoing global Parkinson’s disease Project about disease progression with more than 1,000 subjects included. Results from the baseline evaluation. Eur J Neurol 66:151–158
go back to reference Santos García D, Suárez Castro E, Expósito I et al (2017) Comorbid conditions associated with Parkinson’s disease: a longitudinal and comparative study with Alzheimer disease and con-trol subjects. J Neurol Sci 373:210–215CrossRef Santos García D, Suárez Castro E, Expósito I et al (2017) Comorbid conditions associated with Parkinson’s disease: a longitudinal and comparative study with Alzheimer disease and con-trol subjects. J Neurol Sci 373:210–215CrossRef
go back to reference Santos-García D, Mir P, Cubo E, COPPADIS Study Group. COPPADIS-2015 (COhort of Patients with PArkinson’s DIsease in Spain, 2015) et al (2016) a global–clinical evaluations, serum biomarkers, genetic studies and neuroimaging–prospective, multicenter, non-interventional, long-term study on Parkinson’s disease progression. BMC Neurol 16:26CrossRef Santos-García D, Mir P, Cubo E, COPPADIS Study Group. COPPADIS-2015 (COhort of Patients with PArkinson’s DIsease in Spain, 2015) et al (2016) a global–clinical evaluations, serum biomarkers, genetic studies and neuroimaging–prospective, multicenter, non-interventional, long-term study on Parkinson’s disease progression. BMC Neurol 16:26CrossRef
go back to reference Sathe K, Maetzler W, Lang JD et al (2012) S100B is increased in Parkinson’s disease and ablation protects against MPTP-induced toxicity through the RAGE and TNF-α pathway. Brain 135:3336–3347CrossRef Sathe K, Maetzler W, Lang JD et al (2012) S100B is increased in Parkinson’s disease and ablation protects against MPTP-induced toxicity through the RAGE and TNF-α pathway. Brain 135:3336–3347CrossRef
go back to reference Sawada H, Oeda T, Umemura A et al (2014) Subclinical elevation of plasma C-reactive protein and illusions/hallucinations in subjects with Parkinson’s disease: case-control study. PLoS One 9:e85886CrossRef Sawada H, Oeda T, Umemura A et al (2014) Subclinical elevation of plasma C-reactive protein and illusions/hallucinations in subjects with Parkinson’s disease: case-control study. PLoS One 9:e85886CrossRef
go back to reference Sawada H, Oeda T, Umemura A et al (2015) Baseline C-reactive protein levels and life prognosis in Parkinson disease. PLoS One 10:e0134118CrossRef Sawada H, Oeda T, Umemura A et al (2015) Baseline C-reactive protein levels and life prognosis in Parkinson disease. PLoS One 10:e0134118CrossRef
go back to reference Sousa AC, Zunzunegui MV, Li A, Phillips SP, Guralnik JM, Guerra RO (2016) Association between C-reactive protein and physical performance in older populations: results from the International Mobility in Aging Study (IMIAS). Age Ageing 45:274–280CrossRef Sousa AC, Zunzunegui MV, Li A, Phillips SP, Guralnik JM, Guerra RO (2016) Association between C-reactive protein and physical performance in older populations: results from the International Mobility in Aging Study (IMIAS). Age Ageing 45:274–280CrossRef
go back to reference Umemura A, Oeda T, Yamamoto K et al (2015) Baseline plasma C-reactive protein concentrations and motor prognosis in Parkinson disease. PLoS One 10:e0136722CrossRef Umemura A, Oeda T, Yamamoto K et al (2015) Baseline plasma C-reactive protein concentrations and motor prognosis in Parkinson disease. PLoS One 10:e0136722CrossRef
go back to reference van Kan Abellan G, Rolland Y, Andrieu S et al (2009) Gait speed at usual pace as a predictor of adverse outcomes in community-dwelling older people an International Academy on Nutrition and Aging (IANA) task force. J Nutr Health Aging 13:881–889CrossRef van Kan Abellan G, Rolland Y, Andrieu S et al (2009) Gait speed at usual pace as a predictor of adverse outcomes in community-dwelling older people an International Academy on Nutrition and Aging (IANA) task force. J Nutr Health Aging 13:881–889CrossRef
go back to reference Verghese J, Holtzer R, Lipton RB, Wang C (2012) High-sensitivity C-reactive protein and mobility disability in older adults. Age Ageing 41:541–545CrossRef Verghese J, Holtzer R, Lipton RB, Wang C (2012) High-sensitivity C-reactive protein and mobility disability in older adults. Age Ageing 41:541–545CrossRef
go back to reference Zhang H, Yin X, Ouyang Z et al (2016) A prospective study of freezing of gait with early Parkinson disease in Chinese patients. Medicine (Baltimore) 95:e4056CrossRef Zhang H, Yin X, Ouyang Z et al (2016) A prospective study of freezing of gait with early Parkinson disease in Chinese patients. Medicine (Baltimore) 95:e4056CrossRef
Metadata
Title
High ultrasensitive serum C-reactive protein may be related to freezing of gait in Parkinson’s disease patients
Authors
Diego Santos-García
T. de Deus Fonticoba
E. Suárez Castro
A. Aneiros Díaz
J. M. Paz González
M. J. Feal Panceiras
C. García Sancho
S. Jesús
P. Mir
M. Aguilar
P. Pastor
J. Hernández Vara
O. de Fábregues-Boixar
V. Puente
A. Crespo Cuevas
I. González-Aramburu
J. Infante
F. Carrillo Padilla
M. Pueyo
S. Escalante
N. Bernardo
B. Solano
A. Cots Foraster
P. Martinez-Martin
on behalf of the COPPADIS Study Group
Publication date
01-12-2019
Publisher
Springer Vienna
Published in
Journal of Neural Transmission / Issue 12/2019
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI
https://doi.org/10.1007/s00702-019-02096-8

Other articles of this Issue 12/2019

Journal of Neural Transmission 12/2019 Go to the issue

Psychiatry and Preclinical Psychiatric Studies - Short communication

Association between cognitive performance and SYT1-rs2251214 among women with cocaine use disorder

Neurology and Preclinical Neurological Studies - Original Article

Vitamin D rise enhances blood perfusion in patients with multiple sclerosis