Biomarkers and non-motor symptoms as a function of motor symptom asymmetry in early Parkinson's disease

Voruz, Philippe; Constantin, Ioana Medeleine; Péron, Julie Anne

doi:10.1016/j.neuropsychologia.2022.108419

Cited by 7 publications

(5 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This could be explained by the fact that a substantial part of cognitive and affective processes is underpinned by bilateral neuronal networks, implicating thus a potential influence of compensatory processes at the beginning of the pathology [ 65 ]. Moreover, complex interactions with other biomarkers (e.g., total-tau; α-synuclein; Aβ42), for which distinct profiles have been recently highlighted between LPD and RPD patients [ 66 , 67 ] might explain these results. Therefore, there seem to be distinct mechanisms through which UA moderates cognitive and psychiatric symptoms in early PD, notably depending on sex and motor symptom asymmetry.…”

Section: Discussionmentioning

confidence: 99%

“…These results comfort previous studies that found greater cognitive impairment in PD men than women [ 68 ], as well as recent longitudinal studies in early and advanced asymmetric PD that found a greater progression of cognitive impairment in RPD, specifically for global cognitive efficiency and memory function, alongside higher levels of apathy, suggesting a potential risk factor for dementia associated with PD. Conversely, results for LPD patients have revealed higher psychiatric symptoms, such as depression and anxiety, as well as emotional recognition disorders [ 10 , 66 , 69 – 71 ]. One explanation could reside in sex-related differences in hemispheric lateralization that might further allow to understand the observed cognitive and psychiatric discrepancies between subgroups.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Moderating effects of uric acid and sex on cognition and psychiatric symptoms in asymmetric Parkinson’s disease

2023

Self Cite

View full text Add to dashboard Cite

Background Non-motor symptoms are an important early feature of Parkinson’s disease (PD), encompassing a variety of cognitive and psychiatric symptoms that seem to manifest differently depending on motor symptom asymmetry. Different factors, such as uric acid (UA) and sex, seem to influence cognitive and psychiatric expression in PD, however their interplay remains to be better understood. Methods Participants taking part in the Parkinson’s Progression Marker Initiative were studied based on the side of motor symptom asymmetry and sex. Three-way interaction modeling was used to examine the moderating effects of sex and UA on cognitive functions and psychiatric symptoms. Results Significant three-way interactions were highlighted at 1-year follow-up between motor symptom asymmetry, UA and sex for immediate and long-term memory in female patients exhibiting predominantly left-sided motor symptoms, and for processing speed and sleepiness in female patients exhibiting predominantly right-sided motor symptoms. No significant interactions were observed for male patients. Moreover, female patients exhibiting predominantly right-sided motor symptoms demonstrated lower serum UA concentrations and had overall better outcomes, while male patients with predominantly right-sided motor symptoms demonstrated particularly poor outcomes. Conclusions These findings suggest that in the earliest stages of the disease, UA and sex moderate cognitive functions and psychiatric symptoms differently depending on motor asymmetry, holding important clinical implications for symptom management in patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Moderating effects of uric acid and sex on cognition and psychiatric symptoms in asymmetric Parkinson’s disease

2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…Mencarelli and Martinez-Martinez 8, 9 . In PD trajectories, a susceptibility to left hemispheric asymmetry would be associated with an increased risk of developing dementia compared to right asymmetry 13,15 .…”

Section: Discussionmentioning

confidence: 99%

“…It would therefore seem that variations in the concentration of glucosylceramides in the cerebrospinal uid are associated with the possibility to differentiate idiopathic PwPD phenotypes by taking genetic factors into account 11 . In view of recent studies showing differences in motor (MDS-UPDRS III) 12 and cognitive (MoCA) 13 symptoms according to striatal degeneration asymmetry, as well as studies highlighting relationships between ceramides and neurodegenerative processes, a better understanding of the relationship between metabolism and cognition as a function of striatal dopaminergic denervation asymmetry seems of crucial interest 2,11,14 .…”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal fluid ceramides and cognition as a function of striatal asymmetry in early Parkinson's disease

Péron

Nuber-Champier

Voruz

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

A growing interest in studying the impact of brain asymmetry on physiological markers and cognition in people with Parkinson's disease (PwPD) recently emerged. The aim of this study was to test the impact of striatal denervation asymmetry on brain markers such as ceramides accumulation (ng/ml), as well as its impact on cognitive performances in early PwPD. We analysed data from 329 PwPD patients at the beginning of the disease (mean 6.9 months after diagnosis) (72 left-asymmetric, 83 right-asymmetric and 174 symmetric PwPD) and 167 healthy controls. Asymmetry was based on the difference in putamen denervation greater than 20%. Patients with genetic mutations were excluded. We performed generalized linear mixed models introducing the amount of cerebrospinal fluid ceramides (ng/ml) and cognitive functions as discriminating factors. Finally, Spearman correlations were used to highlight the relationship between cognition and cerebrospinal fluid ceramides on the whole pathological group and within each sub-group, as a function of striatal denervation asymmetry. First, a reduced concentration of ceramide (C18:0 CER) in the symmetrical group compared to the asymmetrical group and the control group was observed. More specifically left denervation predominant PwPD had significantly more ceramides (C22:0 CER) than the right and controls. Second, poorer cognitive performance for the symmetric group compared to the asymmetric and control groups was reported. Overall, positive correlations between cognition and ceramides (C18:0, C22:0 CER) was observed. Conversely, glucosylceramide correlation (C22:0 GlcCer) showed a negative link with cognition. This study shows that asymmetry of striatal degeneration in early Parkinson's disease is accompanied by metabolic variations related to cognitive processes.

show abstract

“…Molecular biomarkers could differentiate PD from other disorders, leading to a more accurate diagnosis (Postuma & Lang, 2023). Biomarkers play a critical role in PD research, as they can provide insight into disease pathology, aid in the diagnosis and serve as targets for therapeutic interventions (Surguchov, 2022; Voruz et al, 2022). Since PD is primarily diagnosed based on clinical symptoms, biomarkers can objectively measure disease progression and treatment response (Valencia et al, 2022; Zimmermann & Brockmann, 2022).…”

Section: Introductionmentioning

confidence: 99%

miR‐221 and Parkinson's disease: A biomarker with therapeutic potential

Zamanian,

Ivraghi,

Gupta

et al. 2023

Eur J of Neuroscience

View full text Add to dashboard Cite

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra, leading to various motor and non‐motor symptoms. Several cellular and molecular mechanisms such as alpha‐synuclein (α‐syn) accumulation, mitochondrial dysfunction, oxidative stress and neuroinflammation are involved in the pathogenesis of this disease. MicroRNAs (miRNAs) play important roles in post‐transcriptional gene regulation. They are typically about 21–25 nucleotides in length and are involved in the regulation of gene expression by binding to the messenger RNA (mRNA) molecules. miRNAs like miR‐221 play important roles in various biological processes, including development, cell proliferation, differentiation and apoptosis. miR‐221 promotes neuronal survival against oxidative stress and neurite outgrowth and neuronal differentiation. Additionally, the role of miR‐221 in PD has been investigated in several studies. According to the results of these studies, (1) miR‐221 protects PC12 cells against oxidative stress induced by 6‐hydroxydopamine; (2) miR‐221 prevents Bax/caspase‐3 signalling activation by stopping Bim; (3) miR‐221 has moderate predictive power for PD; (4) miR‐221 directly targets PTEN, and PTEN over‐expression eliminates the protective action of miR‐221 on p‐AKT expression in PC12 cells; and (5) miRNA‐221 controls cell viability and apoptosis by manipulating the Akt signalling pathway in PD. This review study suggested that miR‐221 has the potential to be used as a clinical biomarker for PD diagnosis and stage assignment.

show abstract

Biomarkers and non-motor symptoms as a function of motor symptom asymmetry in early Parkinson's disease

Cited by 7 publications

References 61 publications

Moderating effects of uric acid and sex on cognition and psychiatric symptoms in asymmetric Parkinson’s disease

Moderating effects of uric acid and sex on cognition and psychiatric symptoms in asymmetric Parkinson’s disease

Cerebrospinal fluid ceramides and cognition as a function of striatal asymmetry in early Parkinson's disease

miR‐221 and Parkinson's disease: A biomarker with therapeutic potential

Contact Info

Product

Resources

About