scholarly journals Texture-based markers from structural imaging correlate with motor handicap in Parkinson’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nacim Betrouni ◽  
Caroline Moreau ◽  
Anne-Sophie Rolland ◽  
Nicolas Carrière ◽  
Marie Chupin ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Stage ◽  
Morphological Changes ◽  
Texture Features ◽  
Nigrostriatal Pathway ◽  
Treatment Conditions ◽  
Patient Groups ◽  
Weighted Sequences ◽  
Motor Handicap

AbstractThere is a growing need for surrogate biomarkers for Parkinson’s disease (PD). Structural analysis using magnetic resonance imaging with T1-weighted sequences has the potential to quantify histopathological changes. Degeneration is typically measured by the volume and shape of morphological changes. However, these changes appear late in the disease, preventing their use as surrogate markers. We investigated texture changes in 108 individuals, divided into three groups, matched in terms of sex and age: (1) healthy controls (n = 32); (2) patients with early-stage PD (n = 39); and (3) patients with late-stage PD and severe L-dopa-related complications (n = 37). All patients were assessed in off-treatment conditions. Statistical analysis of first- and second-order texture features was conducted in the substantia nigra, striatum, thalamus and sub-thalamic nucleus. Regions of interest volumetry and voxel-based morphometry were performed for comparison. Significantly different texture features were observed between the three populations, with some showing a gradual linear progression between the groups. The volumetric changes in the two PD patient groups were not significantly different. Texture features were significantly associated with clinical scores for motor handicap. These results suggest that texture features, measured in the nigrostriatal pathway at PD diagnosis, may be useful in predicting clinical progression of motor handicap.

Retinal Morphological Changes during the Two Years of Follow-Up in Parkinson's Disease

2020 ◽  
Author(s):  
Mahmut Atum ◽  
Bekir Enes Demiryurek
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
Early Stage ◽  
Morphological Changes ◽  
Fiber Layer ◽  
Significant Difference ◽  
Yahr Scale ◽  
And Control

Abstract Background: The study aims to investigate the relationship between the progression of idiopathic Parkinson's disease (IPD) and retinal morphology. Methods: The study was carried out with 23 patients diagnosed with early-stage IPD (phases 1 and 2 of the Hoehn and Yahr scale) and 30 age-matched healthy controls. All patients were followed up at least two years, with 6-month intervals (initial, 6th month, 12th month, 18th month, and 24th month), and detailed neurological and ophthalmic examinations were performed at each follow-up. Unified Parkinson's Disease Rating Scale part III (UPDRS Part III) scores, Hoehn and Yahr (H&Y) scores, best-corrected visual acuity (BCVA), intraocular pressure (IOP) measurement, central macular thickness (CMT) and retinal nerve fiber layer (RNFL) thickness were analyzed at each visit. Results: The average age of the IPD and control groups was 43.96 ± 4.88 years, 44.53 ± 0.83 years, respectively. The mean duration of the disease in the IPD group was 7.48 ± 5.10 months at the start of the study (range 0-16). There was no statistically significant difference in BCVA and IOP values between the two groups during the two-year follow-up period (p> 0.05, p> 0.05, respectively). Average and superior quadrant RNFL thicknesses were statistically different between the two groups at 24 months and there was no significant difference between other visits (p = 0.025, p=0.034, p> 0.05, respectively). There was no statistically significant difference in CMT between the two groups during the follow-up period (p> 0.05). Conclusion: Average and superior quadrant RNFL thicknesses were significantly thinning with the progression of IPD.

Possible selves and illness: A comparison of individuals with Parkinson's disease, early-stage Alzheimer's disease, and healthy older adults

2003 ◽  
Vol 27 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Leslie D. Frazier ◽  
Victoria Cotrell ◽  
Karen Hooker
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Possible Selves ◽  
Early Stage ◽  
Healthy Older Adults ◽  
Patient Groups ◽  
The Impact

This study examined how future self-representations are affected by two different chronic illnesses, one focused on cognitive losses, early-stage Alzheimer's disease (AD), and one focused on physical losses, Parkinson's disease (PD). The impact of illness on possible selves (perceptions of self in the future) was made salient by a comparison with healthy older adults in order to better understand developmental issues in later life. Findings show that although there were no differences in the total number of domains reported by the groups, specific domains were reported differently by patient groups and all domains were likely to become infused with illness. As expected, patient groups had less self-efficacy and lower outcome expectancies for their future selves, and PD patients reported less distance from their feared selves. Although these findings are intuitive, this is the first empirical effort to document the impact of illness on older adults' self-representations. Group differences are explained in terms of disease context, and the importance of possible selves and self-regulatory functions as therapeutic mechanisms for adaptation to illness are emphasised.

scholarly journals Focused ultrasound enhanced intranasal delivery of brain derived neurotrophic factor produces neurorestorative effects in a Parkinson’s disease mouse model

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Robin Ji ◽  
Morgan Smith ◽  
Yusuke Niimi ◽  
Maria E. Karakatsani ◽  
Maria F. Murillo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Neurotrophic Factor ◽  
Focused Ultrasound ◽  
Neurodegenerative Disorder ◽  
Control Function ◽  
Early Stage ◽  
Brain Derived Neurotrophic Factor ◽  
Nigrostriatal Pathway

AbstractFocused ultrasound-enhanced intranasal (IN + FUS) delivery is a noninvasive approach that utilizes the olfactory pathway to administer pharmacological agents directly to the brain, allowing for a more homogenous distribution in targeted locations compared to IN delivery alone. However, whether such a strategy has therapeutic values, especially in neurodegenerative disorders such as Parkinson’s disease (PD), remains to be established. Herein, we evaluated whether the expression of tyrosine hydroxylase (TH), the rate limiting enzyme in dopamine catalysis, could be enhanced by IN + FUS delivery of brain-derived neurotrophic factor (BDNF) in a toxin-based PD mouse model. Mice were put on the subacute dosing regimen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), producing bilateral degeneration of the nigrostriatal pathway consistent with early-stage PD. MPTP mice then received BDNF intranasally followed by multiple unilateral FUS-induced blood-brain barrier (BBB) openings in the left basal ganglia for three consecutive weeks. Subsequently, mice were survived for two months and were evaluated morphologically and behaviorally to determine the integrity of their nigrostriatal dopaminergic pathways. Mice receiving IN + FUS had significantly increased TH immunoreactivity in the treated hemisphere compared to the untreated hemisphere while mice receiving only FUS-induced BBB opening or no treatment at all did not show any differences. Additionally, behavioral changes were only observed in the IN + FUS treated mice, indicating improved motor control function in the treated hemisphere. These findings demonstrate the robustness of the method and potential of IN + FUS for the delivery of bioactive factors for treatment of neurodegenerative disorder.

scholarly journals Retinal morphological changes during the two years of follow-up in Parkinson’s disease

2021 ◽  
Vol 74 (1-2) ◽  
pp. 57-63
Author(s):  
Mahmut Atum ◽  
Bekir Enes Demiryürek
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
Early Stage ◽  
Morphological Changes ◽  
Fiber Layer ◽  
Significant Difference ◽  
Yahr Scale ◽  
And Control

The study aims to investigate the relationship between the progression of idiopathic Parkinson’s disease (IPD) and retinal morphology. The study was carried out with 23 patients diagnosed with early-stage IPD (phases 1 and 2 of the Hoehn and Yahr scale) and 30 age-matched healthy controls. All patients were followed up at least two years, with 6-month intervals (initial, 6th month, 12th month, 18th month, and 24th month), and detailed neurological and ophthalmic examinations were performed at each follow-up. Unified Parkinson’s Disease Rating Scale part III (UPDRS Part III) scores, Hoehn and Yahr (H&Y) scores, best-corrected visual acuity (BCVA), intraocular pressure (IOP) measurement, central macular thickness (CMT) and retinal nerve fiber layer (RNFL) thickness were analyzed at each visit. The average age of the IPD and control groups was 43.96 ± 4.88 years, 44.53 ± 0.83 years, respectively. The mean duration of the disease in the IPD group was 7.48 ± 5.10 months at the start of the study (range 0-16). There was no statistically significant difference in BCVA and IOP values between the two groups during the two-year follow-up period (p> 0.05, p> 0.05, respectively). Average and superior quadrant RNFL thicknesses were statistically different between the two groups at 24 months and there was no significant difference between other visits (p=0.025, p=0.034, p> 0.05, respectively). There was no statistically significant difference in CMT between the two groups during the follow-up period (p> 0.05). Average and superior quadrant RNFL thicknesses were significantly thinning with the progression of IPD.

Association of the Non-Motor Burden with Patterns of Striatal Dopamine Loss in de novo Parkinson’s Disease

2020 ◽  
Vol 10 (4) ◽  
pp. 1541-1549
Author(s):  
Seok Jong Chung ◽  
Sangwon Lee ◽  
Han Soo Yoo ◽  
Yang Hyun Lee ◽  
Hye Sun Lee ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
De Novo ◽  
Early Stage ◽  
Striatal Dopamine ◽  
Motor Deficits ◽  
Dopamine Depletion ◽  
Severe Motor ◽  
Severe Group ◽  
Striatal Dopamine Depletion

Background: Striatal dopamine deficits play a key role in the pathogenesis of Parkinson’s disease (PD), and several non-motor symptoms (NMSs) have a dopaminergic component. Objective: To investigate the association between early NMS burden and the patterns of striatal dopamine depletion in patients with de novo PD. Methods: We consecutively recruited 255 patients with drug-naïve early-stage PD who underwent 18F-FP-CIT PET scans. The NMS burden of each patient was assessed using the NMS Questionnaire (NMSQuest), and patients were divided into the mild NMS burden (PDNMS-mild) (NMSQuest score <6; n = 91) and severe NMS burden groups (PDNMS-severe) (NMSQuest score >9; n = 90). We compared the striatal dopamine transporter (DAT) activity between the groups. Results: Patients in the PDNMS-severe group had more severe parkinsonian motor signs than those in the PDNMS-mild group, despite comparable DAT activity in the posterior putamen. DAT activity was more severely depleted in the PDNMS-severe group in the caudate and anterior putamen compared to that in the PDMNS-mild group. The inter-sub-regional ratio of the associative/limbic striatum to the sensorimotor striatum was lower in the PDNMS-severe group, although this value itself lacked fair accuracy for distinguishing between the patients with different NMS burdens. Conclusion: This study demonstrated that PD patients with severe NMS burden exhibited severe motor deficits and relatively diffuse dopamine depletion throughout the striatum. These findings suggest that the level of NMS burden could be associated with distinct patterns of striatal dopamine depletion, which could possibly indicate the overall pathological burden in PD.

Gene expression analysis in modeling Parkinson’s disease

2020 ◽  
pp. 103-104
Author(s):  
М.М. Руденок ◽  
А.Х. Алиева ◽  
А.А. Колачева ◽  
М.В. Угрюмов ◽  
П.А. Сломинский ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Stage ◽  
Systemic Disease ◽  
Molecular Genetic ◽  
Presymptomatic Stage ◽  
Whole Transcriptome Analysis ◽  
Whole Transcriptome ◽  
The Brain ◽  
Transcriptome Level

Несмотря на очевидный прогресс, достигнутый в изучении молекулярно-генетических факторов и механизмов патогенеза болезни Паркинсона (БП), в настоящее время стало ясно, что нарушения в структуре ДНК не описывают весь спектр патологических изменений, наблюдаемых при развитии заболевания. В настоящее время показано, что существенное влияние на патогенез БП могут оказывать изменения на уровне транскриптома. В работе были использованы мышиные модели досимптомной стадии БП, поздней досимптомной и ранней симптомной (РСС) стадиями БП. Для полнотранскриптомного анализа пулов РНК тканей черной субстанции и стриатума мозга мышей использовались микрочипы MouseRef-8 v2.0 Expression BeadChip Kit («Illumina», США). Полученные данные указывают на последовательное вовлечение транскриптома в патогенез БП, а также на то, что изменения на транскриптомном уровне процессов транспорта и митохондриального биогенеза могут играть важную роль в нейродегенерации при БП уже на самых ранних этапах. Parkinson’s disease (PD) is a complex systemic disease, mainly associated with the death of dopaminergic neurons. Despite the obvious progress made in the study of molecular genetic factors and mechanisms of PD pathogenesis, it has now become clear that violations in the DNA structure do not describe the entire spectrum of pathological changes observed during the development of the disease. It has now been shown that changes at the transcriptome level can have a significant effect on the pathogenesis of PD. The authors used models of the presymptomatic stage of PD with mice decapitation after 6 hours (6 h-PSS), presymptomatic stage with decapitation after 24 hours (24 h-PSS), advanced presymptomatic (Adv-PSS) and early symptomatic (ESS) stages of PD. For whole transcriptome analysis of RNA pools of the substantia nigra and mouse striatum, the MouseRef-8 v2.0 Expression BeadChip Kit microchips (Illumina, USA) were used. As a result of the analysis of whole transcriptome data, it was shown that, there are a greater number of statistically significant changes in the tissues of the brain and peripheral blood of mice with Adv-PSS and ESS models of PD compared to 6 h-PSS and 24 h-PSS models. In general, the obtained data indicate the sequential involvement of the transcriptome in the pathogenesis of PD, as well as the fact that changes at the transcriptome level of the processes of transport and mitochondrial biogenesis can play an important role in neurodegeneration in PD at an early stage.

scholarly journals Holistic Metabolomic Laboratory-Developed Test (LDT): Development and Use for the Diagnosis of Early-Stage Parkinson’s Disease

Metabolites ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 14
Author(s):  
Petr G. Lokhov ◽  
Dmitry L. Maslov ◽  
Steven Lichtenberg ◽  
Oxana P. Trifonova ◽  
Elena E. Balashova
Keyword(s):  
Parkinson’S Disease ◽  
Molecular Weight ◽  
Parkinson's Disease ◽  
High Resolution Mass Spectrometry ◽  
Early Stage ◽  
Disease Diagnosis ◽  
The Body ◽  
Low Molecular Weight ◽  
Low Molecular Weight Compounds

A laboratory-developed test (LDT) is a type of in vitro diagnostic test that is developed and used within a single laboratory. The holistic metabolomic LDT integrating the currently available data on human metabolic pathways, changes in the concentrations of low-molecular-weight compounds in the human blood during diseases and other conditions, and their prevalent location in the body was developed. That is, the LDT uses all of the accumulated metabolic data relevant for disease diagnosis and high-resolution mass spectrometry with data processing by in-house software. In this study, the LDT was applied to diagnose early-stage Parkinson’s disease (PD), which currently lacks available laboratory tests. The use of the LDT for blood plasma samples confirmed its ability for such diagnostics with 73% accuracy. The diagnosis was based on relevant data, such as the detection of overrepresented metabolite sets associated with PD and other neurodegenerative diseases. Additionally, the ability of the LDT to detect normal composition of low-molecular-weight compounds in blood was demonstrated, thus providing a definition of healthy at the molecular level. This LDT approach as a screening tool can be used for the further widespread testing for other diseases, since ‘omics’ tests, to which the metabolomic LDT belongs, cover a variety of them.

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