Heterogeneity of Cholinergic Denervation in Parkinson's Disease without Dementia

Parkinson's disease (PD) is a multisystem neurodegenerative disorder. Heterogeneous clinical features may reflect heterogeneous changes in different brain regions. In contrast to the pronounced nigrostriatal denervation characteristic of PD, cholinergic changes are less marked. We investigated cholinergic innervation activity in PD subjects relative to normal subjects. Nondemented PD subjects ( n=101, age 65.3±7.2 years) and normal subjects ( n=29, age 66.8±10.9 years) underwent clinical assessment and [11C]methyl-4-piperidinyl propionate acetylcholinesterase and [11C]dihydrotetrabenazine monoaminergic positron emission tomography (PET) imaging. Cholinergic projection changes were heterogeneous for 65 out of 101 PD subjects who had neocortical and thalamic acetylcholinesterase activity within the normal range. The remainder had combined neocortical and thalamic (13/101), isolated neocortical (18/101), or isolated thalamic (5/101) acetylcholinesterase activity below the normal range. The low neocortical acetylcholinesterase activity subgroup had significantly lower global cognitive performance compared with the normal range subgroup (F=7.64, P=0.0069) with an independent effect for nigrostriatal denervation (F=7.60, P=0.0074). The low thalamic acetylcholinesterase activity subgroup did not differ from the normal thalamic acetylcholinesterase activity subgroup in cognitive performance or motor impairments except for a history of falls ( P=0.0023). Cholinergic denervation is heterogeneous with reduced neocortical and/or thalamic acetylcholinesterase activity in 36% of nondemented PD subjects with corresponding clinical phenotypic variation. Results also show independent cognitive effects for both cholinergic and dopaminergic system changes in nondemented PD subjects.

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Differentiating Progressive Supranuclear Palsy and Parkinson's Disease With Head-Mounted Displays

Frontiers in Neurology ◽

10.3389/fneur.2021.791366 ◽

2021 ◽

Vol 12 ◽

Author(s):

Arvid Herwig ◽

Almedin Agic ◽

Hans-Jürgen Huppertz ◽

Randolf Klingebiel ◽

Frédéric Zuhorn ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Eye Movements ◽

Progressive Supranuclear Palsy ◽

Neurodegenerative Disorder ◽

High Sensitivity ◽

Brain Regions ◽

Inpatient Setting ◽

Head Mounted Displays ◽

Diagnostic Index

Background: Progressive supranuclear palsy (PSP) is a neurodegenerative disorder that, especially in the early stages of the disease, is clinically difficult to distinguish from Parkinson's disease (PD).Objective: This study aimed at assessing the use of eye-tracking in head-mounted displays (HMDs) for differentiating PSP and PD.Methods: Saccadic eye movements of 13 patients with PSP, 15 patients with PD, and a group of 16 healthy controls (HCs) were measured. To improve applicability in an inpatient setting and standardize the diagnosis, all the tests were conducted in a HMD. In addition, patients underwent atlas-based volumetric analysis of various brain regions based on high-resolution MRI.Results: Patients with PSP displayed unique abnormalities in vertical saccade velocity and saccade gain, while horizontal saccades were less affected. A novel diagnostic index was derived, multiplying the ratios of vertical to horizontal gain and velocity, allowing segregation of PSP from PD with high sensitivity (10/13, 77%) and specificity (14/15, 93%). As expected, patients with PSP as compared with patients with PD showed regional atrophy in midbrain volume, the midbrain plane, and the midbrain tegmentum plane. In addition, we found for the first time that oculomotor measures (vertical gain, velocity, and the diagnostic index) were correlated significantly to midbrain volume in the PSP group.Conclusions: Assessing eye movements in a HMD provides an easy to apply and highly standardized tool to differentiate PSP of patients from PD and HCs, which will aid in the diagnosis of PSP.

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The development of visual neuroimaging research of acupuncture in the treatment of Parkinson’s disease

Brain Science Advances ◽

10.26599/bsa.2019.9050016 ◽

2019 ◽

Vol 5 (3) ◽

pp. 161-168 ◽

Cited By ~ 1

Author(s):

Yuan Yang ◽

Suhua Miao ◽

Rongsong Zhou ◽

Yu Ma ◽

Yuqi Zhang

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Neuronal Activity ◽

Structural Changes ◽

Neurodegenerative Disorder ◽

Cerebral Metabolism ◽

Experimental Studies ◽

Brain Regions ◽

Imaging Studies ◽

Surgical Treatments

Parkinson’s disease (PD) is a progressive neurodegenerative disorder commonly observed in middle-aged and elderly. Currently, its etiology and pathogenesis are still not completely understood. It is associated with many symptoms that severely affect patients’ health and quality of life. At present, the PD clinical treatment mainly aimed to alleviate symptoms, and both medicinal and surgical treatments have side effects and treatment blind spots. The use of acupuncture for the treatment of PD is relatively widespread, and its safety and efficacy have been gradually accepted by the public and medical professions. However, the efficacy of acupuncture in experimental studies remains controversial. Therefore, this paper reviews imaging studies on the use of acupuncture for the treatment of PD. From the study, it shows that acupuncture can improve the neuronal activity, activate the neuronal activity in damaged brain regions, affect relevant neural networks and brain circulation, improve cerebral metabolism, and cause structural changes in related brain regions. Intuitive and visible imaging studies provide objective bases on the use of acupuncture for the treatment of PD.

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Directed brain connectivity identifies widespread functional network changes in Parkinson’s disease

10.1101/2021.01.04.425206 ◽

2021 ◽

Author(s):

Mite Mijalkov ◽

Giovanni Volpe ◽

Joana B. Pereira

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Large Scale ◽

Neurodegenerative Disorder ◽

Brain Connectivity ◽

Brain Regions ◽

New Method ◽

Functional Network ◽

Whole Brain ◽

Functional Brain Networks

AbstractParkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by topological changes in large-scale functional brain networks. These networks are commonly analysed using undirected correlations between the activation signals of brain regions. However, this approach suffers from an important drawback: it assumes that brain regions get activated at the same time, despite previous evidence showing that brain activation features causality, with signals being typically generated in one region and then propagated to other ones. Thus, in order to address this limitation, in this study we developed a new method to assess whole-brain directed functional connectivity in patients with PD and healthy controls using anti-symmetric delayed correlations, which capture better this underlying causality. To test the potential of this new method, we compared it to standard connectivity analyses based on undirected correlations. Our results show that whole-brain directed connectivity identifies widespread changes in the functional networks of PD patients compared to controls, in contrast to undirected methods. These changes are characterized by increased global efficiency, clustering and transitivity as well as lower modularity. In addition, changes in the directed connectivity patterns in the precuneus, thalamus and superior frontal gyrus were associated with motor, executive and memory deficits in PD patients. Altogether, these findings suggest that directional brain connectivity is more sensitive to functional network changes occurring in PD compared to standard methods. This opens new opportunities for the analysis of brain connectivity and the development of new brain connectivity markers to track PD progression.

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Multisite non-invasive brain stimulation in Parkinson’s disease: A scoping review

Neurorehabilitation ◽

10.3233/nre-210190 ◽

2021 ◽

pp. 1-17

Author(s):

Camila Beatriz da Silva Machado ◽

Letícia Maria da Silva ◽

Alessandra Feitosa Gonçalves ◽

Palloma Rodrigues de Andrade ◽

Cristina Katya Torres Teixeira Mendes ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Brain Stimulation ◽

Primary Motor Cortex ◽

Neurodegenerative Disorder ◽

Brain Regions ◽

Cochrane Library ◽

Non Invasive ◽

Dorsolateral Prefrontal ◽

Motor Component

BACKGROUND: Parkinson’s Disease (PD) is a progressive neurodegenerative disorder, characterized by cardinal motor symptoms in addition to cognitive impairment. New insights concerning multisite non-invasive brain stimulation effects have been gained, which can now be used to develop innovative treatment approaches. OBJECTIVE: Map the researchs involving multisite non-invasive brain stimulation in PD, synthesize the available evidence and discuss future directions. METHODS: The databases PubMed, PsycINFO, CINAHL, LILACS and The Cochrane Library were searched from inception until April 2020, without restrictions on the date of publication or the language in which it was published. The reviewers worked in pairs and sequentially evaluated the titles, abstracts and then the full text of all publications identified as potentially relevant. RESULTS: Twelve articles met the inclusion criteria. The target brain regions included mainly the combination of a motor and a frontal area, such as stimulation of the primary motor córtex associated with the dorsolateral prefrontal cortex. Most of the trials showed that this modality was only more effective for the motor component, or for the cognitive and/or non-motor, separately. CONCLUSIONS: Despite the results being encouraging for the use of the multisite aproach, the indication for PD management should be carried out with caution and deserves scientific deepening.

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Early Expression of Neuronal Dopaminergic Markers in a Parkinson’s Disease Model in Rats Implanted with Enteric Stem Cells (ENSCs)

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527319666200417123948 ◽

2020 ◽

Vol 19 (2) ◽

pp. 148-162

Author(s):

Carmen Parra-Cid ◽

Eduardo Orozco-Castillo ◽

Julieta García-López ◽

Elena Contreras-Figueroa ◽

Laura E. Ramos-Languren ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Neurodegenerative Disorder ◽

Disease Model ◽

Brain Regions ◽

Substantia Nigra Pars Compacta ◽

Adult Rats ◽

Promising Alternative ◽

Therapeutic Modalities ◽

6 Hydroxydopamine

Background: Parkinson’s Disease (PD) is a common neurodegenerative disorder affecting the dopaminergic (DAergic) system. Replacement therapy is a promising alternative aimed at reconstructing the cytoarchitecture of affected brain regions in PD. Experimental approaches, such as the replacement of DAergic neurons with cells obtained from the Enteric Nervous System (ENS) has yet to be explored. Objective: To establish and characterize a cell replacement strategy with ENS Cells (ENSCs) in a PD model in rats. Methods: Since ENSCs can develop mature DAergic phenotypes, here we cultured undifferentiated cells from the myenteric plexus of newborn rats, establishing that they exhibit multipotential characteristics. These cells were characterized and further implanted in the Substantia nigra pars compacta (SNpc) of adult rats previously lesioned by a retrograde degenerative model produced by intrastriatal injection of 6-Hydroxydopamine (6-OHDA). DAergic markers were assessed in implants to validate their viability and possible differentiation once implanted. Results: Cell cultures were viable, exhibited stem cell features and remained partially undifferentiated until the time of implant. The retrograde lesion induced by 6-OHDA produced DAergic denervation, reducing the number of fibers and cells in the SNpc. Implantation of ENSCs in the SNpc of 6-OHDAlesioned rats was tracked after 5 and 10 days post-implant. During that time, the implant increased selective neuronal and DAergic markers, Including Microtubule-Associated Protein 2 (MAP-2), Dopamine Transporter (DAT), and Tyrosine Hydroxylase (TH). Conclusion: Our novel results suggest that ENSCs possess a differentiating, proliferative and restorative potential that may offer therapeutic modalities to attenuate neurodegenerative events with the inherent demise of DAergic neurons.

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Rapid Diagnosis of Parkinson’s Disease from Sebum using Paper Spray Ionisation Ion Mobility Mass Spectrometry

10.26434/chemrxiv.12517385.v1 ◽

2020 ◽

Author(s):

Depanjan Sarkar ◽

Drupad Trivedi ◽

Eleanor Sinclair ◽

Sze Hway Lim ◽

Caitlin Walton-Doyle ◽

...

Keyword(s):

Mass Spectrometry ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Ion Mobility ◽

Neurodegenerative Disorder ◽

Treatment Options ◽

Ion Mobility Mass Spectrometry ◽

Paper Spray ◽

Molecular Features ◽

Validation Set

Parkinson’s disease (PD) is the second most common neurodegenerative disorder for which identification of robust biomarkers to complement clinical PD diagnosis would accelerate treatment options and help to stratify disease progression. Here we demonstrate the use of paper spray ionisation coupled with ion mobility mass spectrometry (PSI IM-MS) to determine diagnostic molecular features of PD in sebum. PSI IM-MS was performed directly from skin swabs, collected from 34 people with PD and 30 matched control subjects as a training set and a further 91 samples from 5 different collection sites as a validation set. PSI IM-MS elucidates ~ 4200 features from each individual and we report two classes of lipids (namely phosphatidylcholine and cardiolipin) that differ significantly in the sebum of people with PD. Putative metabolite annotations are obtained using tandem mass spectrometry experiments combined with accurate mass measurements. Sample preparation and PSI IM-MS analysis and diagnosis can be performed ~5 minutes per sample offering a new route to for rapid and inexpensive confirmatory diagnosis of this disease.

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Visual Effects of Deep Brain Stimulation in a Patient with Parkinson’s Disease

Vision Development & Rehabilitation ◽

10.31707/vdr2019.5.3.p158 ◽

2019 ◽

pp. 158-173

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Visual System ◽

Brain Stimulation ◽

Neurodegenerative Disorder ◽

Initial Examination ◽

Before And After ◽

Deep Brain ◽

Cover Test

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder caused by a dopamine deficiency that presents with motor symptoms. Visual disorders can occur concomitantly but are frequently overlooked. Deep brain stimulation (DBS) has been an effective treatment to improve tremors, stiffness and overall mobility, but little is known about its effects on the visual system. Case Report: A 75-year-old Caucasian male with PD presented with longstanding binocular diplopia. On baseline examination, the best-corrected visual acuity was 20/25 in each eye. On observation, he had noticeable tremors with an unsteady gait. Distance alternating cover test showed exophoria with a right hyperphoria. Near alternating cover test revealed a significantly larger exophoria accompanied by a reduced near point of convergence. Additional testing with a 24-2 Humphrey visual field and optical coherence tomography (OCT) of the nerve and macula were unremarkable. The patient underwent DBS implantation five weeks after initial examination, and the device was activated four weeks thereafter. At follow up, the patient still complained of intermittent diplopia. There was no significant change in the manifest refraction or prism correction. On observation, the patient had remarkably improved tremors with a steady gait. All parameters measured were unchanged. The patient was evaluated again seven months after device activation. Although vergence ranges at all distances were improved, the patient was still symptomatic for intermittent diplopia. OCT scans of the optic nerve showed borderline but symmetric thinning in each eye. All other parameters measured were unchanged. Conclusion: The case found no significant changes on ophthalmic examination after DBS implantation and activation in a patient with PD. To the best of the authors’ knowledge, there are no other cases in the literature that investigated the effects of DBS on the visual system pathway in a patient with PD before and after DBS implantation and activation.

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Peripheral Immunity, Immunoaging and Neuroinflammation in Parkinson’s Disease

Current Medicinal Chemistry ◽

10.2174/0929867325666181009161048 ◽

2019 ◽

Vol 26 (20) ◽

pp. 3719-3753 ◽

Cited By ~ 10

Author(s):

Natasa Kustrimovic ◽

Franca Marino ◽

Marco Cosentino

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Immune System ◽

Neurodegenerative Disorder ◽

Neurodegenerative Process ◽

Progressive Degeneration ◽

Cytokine Levels ◽

Inflammatory Phenotype ◽

Immune Challenges

:Parkinson’s disease (PD) is the second most common neurodegenerative disorder among elderly population, characterized by the progressive degeneration of dopaminergic neurons in the midbrain. To date, exact cause remains unknown and the mechanism of neurons death uncertain. It is typically considered as a disease of central nervous system (CNS). Nevertheless, numerous evidence has been accumulated in several past years testifying undoubtedly about the principal role of neuroinflammation in progression of PD. Neuroinflammation is mainly associated with presence of activated microglia in brain and elevated levels of cytokine levels in CNS. Nevertheless, active participation of immune system as well has been noted, such as, elevated levels of cytokine levels in blood, the presence of auto antibodies, and the infiltration of T cell in CNS. Moreover, infiltration and reactivation of those T cells could exacerbate neuroinflammation to greater neurotoxic levels. Hence, peripheral inflammation is able to prime microglia into pro-inflammatory phenotype, which can trigger stronger response in CNS further perpetuating the on-going neurodegenerative process.:In the present review, the interplay between neuroinflammation and the peripheral immune response in the pathobiology of PD will be discussed. First of all, an overview of regulation of microglial activation and neuroinflammation is summarized and discussed. Afterwards, we try to collectively analyze changes that occurs in peripheral immune system of PD patients, suggesting that these peripheral immune challenges can exacerbate the process of neuroinflammation and hence the symptoms of the disease. In the end, we summarize some of proposed immunotherapies for treatment of PD.

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Current Therapeutic Strategies and Perspectives for Neuroprotection in Parkinson’s Disease

Current Pharmaceutical Design ◽

10.2174/1381612826666200217114658 ◽

2020 ◽

Vol 26 (37) ◽

pp. 4738-4746

Author(s):

Mohan K. Ghanta ◽

P. Elango ◽

Bhaskar L. V. K. S.

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Early Diagnosis ◽

Neurodegenerative Disorder ◽

Therapeutic Strategies ◽

Neuroprotective Agents ◽

Striatal Neurons ◽

The Status ◽

Advanced Stages ◽

Dopaminergic Pathways

Parkinson’s disease is a progressive neurodegenerative disorder of dopaminergic striatal neurons in basal ganglia. Treatment of Parkinson’s disease (PD) through dopamine replacement strategies may provide improvement in early stages and this treatment response is related to dopaminergic neuronal mass which decreases in advanced stages. This treatment failure was revealed by many studies and levodopa treatment became ineffective or toxic in chronic stages of PD. Early diagnosis and neuroprotective agents may be a suitable approach for the treatment of PD. The essentials required for early diagnosis are biomarkers. Characterising the striatal neurons, understanding the status of dopaminergic pathways in different PD stages may reveal the effects of the drugs used in the treatment. This review updates on characterisation of striatal neurons, electrophysiology of dopaminergic pathways in PD, biomarkers of PD, approaches for success of neuroprotective agents in clinical trials. The literature was collected from the articles in database of PubMed, MedLine and other available literature resources.

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Analysis of Functional and Cognitive Impairment in Institutionalized Individuals with Movement Disorders

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530319666190311104247 ◽

2019 ◽

Vol 19 (7) ◽

pp. 1022-1031 ◽

Cited By ~ 2

Author(s):

Paula D. Cebrián ◽

Omar Cauli

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Activities Of Daily Living ◽

Cognitive Performance ◽

Functional Impairment ◽

Movement Disorders ◽

Neurological Disorders ◽

Daily Living ◽

Severe Cognitive Impairment

Background: Many neurological disorders lead to institutionalization and can be accompanied in their advanced stages by functional impairment, and progressive loss of mobility, and cognitive alterations. Objective: We analyzed the relationship between functional impairment and cognitive performance and its related subdomains in individuals with Parkinson’s disease, Alzheimer’s disease accompanied by motor dysfunction, and with other neurological disorders characterized by both motor and cognitive problems. Methods: All participants lived in nursing homes (Valencia, Spain) and underwent cognitive evaluation with the Mini-Mental State Examination; functional assessment of independence in activities of daily living using the Barthel score and Katz index; and assessment of mobility with the elderly mobility scale. Results: The mean age of the subjects was 82.8 ± 0.6 years, 47% of the sample included individuals with Parkinson’s disease, and 48 % of the sample presented severe cognitive impairment. Direct significant relationships were found between the level of cognitive impairment and functional capacity (p < 0.01) and mobility (p < 0.05). Among the different domains, memory impairment was not associated with altered activities of daily living or mobility. The functional impairment and the risk of severe cognitive impairment were significantly (p<0.05) higher in female compared to male patients. Among comorbidities, overweight/obesity and diabetes were significantly (p < 0.05) associated with poor cognitive performance in those individuals with mild/moderate cognitive impairment. Conclusion: In institutionalized individuals with movement disorders there is an association between functional and cognitive impairment. Reduction of over-weight and proper control of diabetes may represent novel targets for improving cognitive function at such early stages.

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