Highlights
- •Parkinson's disease (PD) patients appear to show increased homocysteine levels.
- •Homocysteine correlated in turn with cognitive performance in our PD sample.
- •Homocysteine was also associated with cortical macro- and microstructural alterations.
- •This metabolic marker may play a role in cortical degeneration in the PD population.
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.
Keywords
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References
- Epidemiology of Parkinson’s disease.Lancet Neurol. 2006; 5: 525-535https://doi.org/10.1016/S1474-4422(06)70471-9
- NMSS validation group, the impact of non-motor symptoms on health-related quality of life of patients with Parkinson’s disease.Mov. Disord. 2011; 26: 399-406https://doi.org/10.1002/mds.23462
- Sampaio, the collaborators of the Parkinson’s disease update on non-motor symptoms study group on behalf of the movement disorders society evidence-based medicine committee, update on treatments for nonmotor symptoms of Parkinson’s disease-an evidence-based medicine review.Mov. Disord. 2019; 34: 180-198https://doi.org/10.1002/mds.27602
- Cognitive decline in Parkinson disease.Nat. Rev. Neurol. 2017; 13: 217-231https://doi.org/10.1038/nrneurol.2017.27
- Interaction between neuropsychiatric symptoms and cognitive performance in Parkinson’s disease: what do clinical and neuroimaging studies tell us?.Curr. Neurol. Neurosci. Rep. 2018; 18: 91https://doi.org/10.1007/s11910-018-0907-6
- Longitudinal intracortical diffusivity changes in de-novo Parkinson’s disease: a promising imaging biomarker.Parkinsonism Relat. Disord. 2019; 68: 22-25https://doi.org/10.1016/j.parkreldis.2019.09.031
- Dopaminergic degeneration induces early posterior cortical thinning in Parkinson’s disease.Neurobiol. Dis. 2019; 124: 29-35https://doi.org/10.1016/j.nbd.2018.11.001
- Serum neurofilament light chain levels reflect cortical neurodegeneration in de novo Parkinson’s disease.Parkinsonism Relat. Disord. 2020; 74: 43-49https://doi.org/10.1016/j.parkreldis.2020.04.009
- Cholinergic denervation patterns across cognitive domains in Parkinson’s disease.Mov. Disord. 2021; 36: 642-650https://doi.org/10.1002/mds.28360
- Neurotransmission in Parkinson’s disease: beyond dopamine.Eur. J. Neurol. 2010; 17: 364-376https://doi.org/10.1111/j.1468-1331.2009.02900.x
- Vascular risk factors and cognition in Parkinson’s disease.J. Alzheimers Dis. 2016; 51: 563-570https://doi.org/10.3233/JAD-150610
- Modifiable risk factors for cognitive impairment in Parkinson’s disease: a systematic review and meta-analysis of prospective cohort studies.Mov. Disord. 2019; 34: 876-883https://doi.org/10.1002/mds.27665
- Modifiable vascular risk factors, white matter disease, and cognition in early Parkinson’s disease.Eur. J. Neurol. 2019; 26: 246-e18https://doi.org/10.1111/ene.13797
- Alzheimer’s disease neuroimaging initiative, summative effects of vascular risk factors on cortical thickness in mild cognitive impairment.Neurobiol. Aging. 2016; 45: 98-106https://doi.org/10.1016/j.neurobiolaging.2016.05.011
- Profiling novel metabolic biomarkers for Parkinson’s disease using in-depth Metabolomic analysis.Mov. Disord. 2017; 32: 1720-1728https://doi.org/10.1002/mds.27173
- Urate: a novel biomarker of Parkinson’s disease risk, diagnosis and prognosis.Biomark. Med. 2010; 4: 701-712https://doi.org/10.2217/bmm.10.94
- Role of homocysteine in the development and progression of Parkinson’s disease.Ann. Clin. Transl. Neurol. 2020; 7: 2332-2338https://doi.org/10.1002/acn3.51227
- Urate and homocysteine: predicting motor and cognitive changes in newly diagnosed Parkinson’s disease.J. Parkinsons Dis. 2019; 9: 351-359https://doi.org/10.3233/JPD-181535
- Homocysteine and cognitive function in Parkinson’s disease.Parkinsonism Relat. Disord. 2017; 44: 1-5https://doi.org/10.1016/j.parkreldis.2017.08.005
- Relationship between serum homocysteine level and cognitive impairment in patients with Parkinson‘s disease.Pteridines. 2019; 30: 177-182https://doi.org/10.1515/pteridines-2019-0023
- Elevated serum homocysteine levels have differential gender-specific associations with motor and cognitive states in Parkinson’s disease.Parkinsons Dis. 2019; 2019: 3124295https://doi.org/10.1155/2019/3124295
- For the dominantly inherited Alzheimer network (DIAN), Biphasic cortical macro- and microstructural changes in autosomal dominant Alzheimer’s disease.Alzheimers Dement. 2021; 17: 618-628https://doi.org/10.1002/alz.12224
- A comparison between voxel-based cortical thickness and voxel-based morphometry in normal aging.Neuroimage. 2009; 48: 371-380https://doi.org/10.1016/j.neuroimage.2009.06.043
- Measuring the thickness of the human cerebral cortex from magnetic resonance images.Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 11050-11055https://doi.org/10.1073/pnas.200033797
- Cortical microstructural changes along the Alzheimer’s disease continuum.Alzheimers Dement. 2018; 14: 340-351https://doi.org/10.1016/j.jalz.2017.09.013
- Catalan frontotemporal dementia initiative (CATFI) and the frontotemporal lobar degeneration neuroimaging initiative (FTLDNI), cortical microstructure in the behavioural variant of frontotemporal dementia: looking beyond atrophy.Brain. 2019; 142: 1121-1133https://doi.org/10.1093/brain/awz031
- Widespread increased diffusivity reveals early cortical degeneration in Huntington disease.AJNR Am. J. Neuroradiol. 2019; 40: 1464-1468https://doi.org/10.3174/ajnr.A6168
- COPPADIS-2015 (COhort of Patients with PArkinson’s DIsease in Spain, 2015), a global--clinical evaluations, serum biomarkers, genetic studies and neuroimaging--prospective, multicenter, non-interventional, long-term study on Parkinson’s disease progression.BMC Neurol. 2016; 16: 26https://doi.org/10.1186/s12883-016-0548-9
- In vivo cholinergic basal forebrain degeneration and cognition in Parkinson’s disease: imaging results from the COPPADIS study.Parkinsonism Relat. Disord. 2021; 88: 68-75https://doi.org/10.1016/j.parkreldis.2021.05.027
- Cortical microstructural correlates of plasma neurofilament light chain in Huntington’s disease.Parkinsonism Relat. Disord. 2021; 85: 91-94https://doi.org/10.1016/j.parkreldis.2021.03.008
- Sex differences in the behavioral variant of frontotemporal dementia: a new window to executive and behavioral reserve.Alzheimers Dement. 2021; https://doi.org/10.1002/alz.12299
- Gender- and age-related differences in homocysteine concentration: a cross-sectional study of the general population of China.Sci. Rep. 2020; 10: 17401https://doi.org/10.1038/s41598-020-74596-7
- Elevated plasma homocysteine levels in patients treated with levodopa: association with vascular disease.Arch. Neurol. 2003; 60: 59-64https://doi.org/10.1001/archneur.60.1.59
- Hyperhomocysteinemia and cardiovascular risk: effect of vitamin supplementation in risk reduction.Curr. Clin. Pharmacol. 2010; 5: 30-36https://doi.org/10.2174/157488410790410551
- Mild cognitive impairment in Parkinson’s disease.J. Neural Transm. (Vienna). 2019; 126: 897-904https://doi.org/10.1007/s00702-019-02003-1
- A divergent breakdown of neurocognitive networks in Parkinson’s disease mild cognitive impairment.Hum. Brain Mapp. 2019; 40: 3233-3242https://doi.org/10.1002/hbm.24593
- The distinct cognitive syndromes of Parkinson’s disease: 5 year follow-up of the CamPaIGN cohort.Brain. 2009; 132: 2958-2969https://doi.org/10.1093/brain/awp245
- Neuropsychological and clinical heterogeneity of cognitive impairment and dementia in patients with Parkinson’s disease.Lancet Neurol. 2010; 9: 1200-1213https://doi.org/10.1016/S1474-4422(10)70212-X
Article info
Publication history
Published online: January 11, 2022
Accepted:
January 5,
2022
Received in revised form:
December 7,
2021
Received:
August 9,
2021
Identification
Copyright
© 2022 Elsevier B.V. All rights reserved.
