39 results found
Zeng Z, Roussakis A-A, Lao-Kaim NP, et al., 2020, Astrocytes in Parkinson's disease: from preclinical assays to in vivo imaging and therapeutic probes, NEUROBIOLOGY OF AGING, Vol: 95, Pages: 264-270, ISSN: 0197-4580
Li W, Lao-Kaim NP, Roussakis A-A, et al., 2020, Longitudinal functional connectivity changes related to dopaminergic decline in Parkinson's disease, NEUROIMAGE-CLINICAL, Vol: 28, ISSN: 2213-1582
Roussakis A, Towey D, Gennaro M, et al., 2019, Parkinson’s disease dyskinesias possibly relate to greater dopamine transporter losses in the putamen over time, Journal of Neurology & Experimental Neuroscience, Vol: 5, Pages: S6-S11, ISSN: 2469-407X
The pathophysiology of levodopa-induced dyskinesias in Parkinson’s disease is incompletely understood. This study was designed to investigate in Parkinson’s patients, whether time-related changes in striatal dopamine transporter availability are associated to the appearance of dyskinesias. 15 Parkinson’s patients had dopamine transporter-specific SPECT imaging with 123I-FP-CIT twice: at baseline (when they were drug naïve) and at follow-up (6.31±2.29 years from baseline), and were followed up clinically every six months. At the end of the study, patients were divided in two groups according to whether they had developed dyskinesias or not. Semi-quantification of 123I-FP-CIT data was performed using the occipital cortex as the reference region. Specific binding ratios were calculated for the putamen and the caudate. During the clinical follow-up, all Parkinson’s patients were treated pharmaceutically. 8 patients developed dyskinesias, while 7 remained nondyskinetic. At baseline, the two groups had similar 123I-FP-CIT specific binding ratio values for the putamen and the caudate (p>0.05). Also, between-group differences in age, disease duration, and Hoehn & Yahr scores were not statistically significant. Over-time, the putaminal 123I-FP-CIT specific binding ratio values in the dyskinetic group decreased significantly (p<0.01). The nondyskinetic patients had smaller reductions (p<0.05) during the same period of time. At follow-up, the dyskinetic patients had significantly higher Hoehn & Yahr scores (p<0.01) and were taking higher levodopa equivalent doses (p<0.001), as compared to the nondyskinetic patients. The development of Parkinson’s dyskinesias is related to a faster progression rate, as reflected by marked putaminal dopamine transporter decreases.
Roussakis A, Lao-Kaim N, Piccini P, 2019, Brain imaging and impulse control disorders in Parkinson’s disease, Current Neurology and Neuroscience Reports, Vol: 19, ISSN: 1528-4042
Purpose of reviewParkinson’s disease (PD) has a wide spectrum of symptoms including the presence of psychiatric disease. At present, most treatment plans, comprised of dopaminergic drugs, are chronic and complex. Though dopaminergic agents are quite efficient in managing the motor aspects of the disease, chronic pharmacotherapy specifically with dopamine receptor agonists has been highly linked to the occurrence of Impulse Compulsive disorder (ICD), which can be problematic for individual patients.Recent findingsMuch of what is known today about PD-related ICD stems from brain imaging studies, however, evidence is not quite conclusive. Research in the field has been focused on identifying the underlying mechanisms of PD-related ICD and understanding the functions of the structures involved in the reward network. SummaryThis article presents an update of recent findings from key neuroimaging studies in PD-related ICD, discusses results from controversial studies, and identifies areas for future research in the field.
Lao-Kaim NP, Martin-Bastida A, Roussakis A-A, et al., 2019, Multimodal imaging of neuromelanin and dopamine transporters in Parkinson's disease reveals asymmetrical relationships within the nigrostriatal system, 5th Congress of the European-Academy-of-Neurology (EAN), Publisher: WILEY, Pages: 99-99, ISSN: 1351-5101
Martin Bastida A, Lao-Kaim N, Roussakis A, et al., 2019, Relationship between neuromelanin and dopamine terminals within the parkinson’s nigrostriatal system, Brain, Vol: 142, Pages: 2023-2036, ISSN: 1460-2156
Parkinson’s disease is characterized by the progressive loss of pigmented dopaminergic neurons in the substantia nigra and associated striatal deafferentation. Neuromelanin content is thought to reflect the loss of pigmented neurons, but available data characterising its relationship with striatal dopaminergic integrity are not comprehensive or consistent, and predominantly involve heterogeneous samples. In this cross-sectional study, we utilised neuromelanin-sensitive magnetic resonance imaging and the highly specific dopamine transporter positron emission tomography radioligand, 11C-PE2I, to assess the association between neuromelanin-containing cell levels in the substantia nigra pars compacta and nigrostriatal terminal density in vivo, in 30 patients with bilateral Parkinson’s disease. Fifteen healthy controls also underwent neuromelanin-sensitive imaging. We used a novel approach taking into account the anatomical and functional subdivision of substantia nigra into dorsal/ventral tiers and striatal nuclei into pre/post-commissural sub-regions, in accordance with previous animal and post-mortem studies, and consider the clinically asymmetric disease presentation. In vivo, Parkinson’s disease subjects displayed reduced neuromelanin levels in the ventral (-30±28%) and dorsal tiers (-21±24%) as compared to the control group (F1,43 = 11.95, P = 0.001). Within the Parkinson’s disease group, nigral pigmentation was lower in the ventral tier as compared to the dorsal tier (F1,29 = 36.19, P < 0.001) and lower in the clinically-defined most affected side (F1,29 = 4.85, P = 0.036). Similarly, lower dopamine transporter density was observed in the ventral tier (F1,29 = 76.39, P < 0.001) and clinically-defined most affected side (F1,29 = 4.21, P = 0.049). Despite similar patterns, regression analysis showed no significant association between nigral pigmentation and nigral dopamine transporter density. However, for the clinically-d
Roussakis A-A, Mohamed MA, Myers J, et al., 2019, Astrogliosis in Parkinson's disease dementia: a preliminary report with brain, 5th Congress of the European-Academy-of-Neurology (EAN)
Hannaway N, Lao-Kaim NP, Martin-Bastida A, et al., 2019, Functional responses to joystick movements during Parkinson's disease progression: a longitudinal fMRI study, 5th Congress of the European-Academy-of-Neurology (EAN), Publisher: WILEY, Pages: 227-227, ISSN: 1351-5101
Roussakis A, Gennaro M, Lao-Kaim N, et al., 2019, Dopamine transporter density in de novo Parkinson’s disease does not relate to the development of levodopa-induced dyskinesias, Journal of Neuroinflammation and Neurodegenerative Diseases, Vol: 3
Background: In Parkinson’s disease (PD), the onset of levodopa-induced dyskinesias (LIDs) is difficult to predict. This study examines whether dopamine transporter (DAT)-specific SPECT imaging in de novo PD relates to later development of LIDs.Methods: 42 de novo unilateral PD participants received DAT-specific SPECT imaging with 123I-FP-CIT at time of diagnosis. At five years post-diagnosis, all PD patients were clinically evaluated and divided into two groups based on whether they had or had not developed LIDs. Fourteen gender- and age-matched healthy volunteers undertook 123I-FP-CIT SPECT imaging and were included as controls. A semi-quantification approach was used for the 123I-FP-CIT data using the occipital cortex as the reference region. We calculated specific binding ratios (SBR) for the caudate and putamen (posterior and anterior putaminal subregions). In parallel, we analysed our 123I-FP-CIT dataset with a voxel-based analysis approach.Results: PD patients had significantly lower striatal 123I-FP-CIT SBR values in comparison to controls (p<0.001). After five years, dyskinetic patients (N=10) were taking higher daily doses of dopaminergic medication (p<0.001) and had more severe disease (difference in Hoehn & Yahr staging scores p<0.05) as compared to the nondyskinetic group (N=32). At the time of diagnosis, 123I-FP-CIT SBR values were not statistically different between the two groups for all striatal regions (p>0.05). SPM voxel-based analysis did not show a statistically significant difference between the two groups (p>0.05).Conclusion: 123I-FP-CIT SPECT imaging, performed at diagnosis in de novo early-stage PD could not differentiate patients who will develop LIDs within five years from those who will not.
Martin-Bastida A, Lao-Kaim N, Pietracupa S, et al., 2018, Assessing working memory dysfunction with letter n-back functional MRI task in early-stage Parkinson's disease, International Congress of Parkinson's Disease and Movement Disorders, Publisher: WILEY, Pages: S688-S688, ISSN: 0885-3185
Roussakis AA, Lao-Kaim N, Martin-Bastida A, et al., 2018, A longitudinal PET study to assess progression of laterality in Parkinson's disease, International Congress of Parkinson's Disease and Movement Disorders, Publisher: WILEY, Pages: S690-S690, ISSN: 0885-3185
Li W, Lao-Kaim N, Roussakis A, et al., 2018, Functional connectivity changes in relation to dopaminergic decline in Parkinson's over time: A resting-state fMRI and 11C-PE2I PET imaging study, International Congress of Parkinson's Disease and Movement Disorders, Publisher: WILEY, Pages: S682-S683, ISSN: 0885-3185
Martin-Bastida A, Lao-Kaim N, Pietracupa S, et al., 2018, Compensatory functional activations in early-stage Parkinson's disease: A cross-sectional motor planning fMRI study, International Congress of Parkinson's Disease and Movement Disorders, Publisher: WILEY, Pages: S653-S653, ISSN: 0885-3185
Roussakis A, Piccini P, 2018, Molecular imaging of neuroinflammation in idiopathic Parkinson's Disease, International Review of Neurobiology, Vol: 141, Pages: 347-363, ISSN: 0074-7742
Neuroinflammation is an important aspect of Parkinson's disease. The study of Parkinson's disease neuroinflammation is quite challenging and is accompanied by controversy. To date, molecular imaging studies have been targeting microglia and more recently astrocytes. In this review article, we discuss the findings from key PET studies with tracers specific for the translocator protein (microglia-specific) and novel evidence from the development of astrocyte-specific PET tracers. We also discuss evidence from pathology studies and in the animal model of Parkinson's disease that form the biological background of current and newer PET neuroinflammation tracers. However, findings from PET imaging studies in microglia have so far not been translated in clinical practice, while no PET study has been conducted in Parkinson's disease specifically targeting astrocytes. Research work is currently focused on (a) identifying new molecular targets for the study of neuroinflammation through PET, (b) assessing the state of neuroinflammation in Parkinson's disease with accuracy and reliability, and (c) developing strategies to modulate the underlying processes of neuroinflammation.
Li W, Lao-Kaim NP, Roussakis A, et al., 2018, Functional connectivity changes in relation to dopaminergic decline in Parkinson's over time: a resting-state fMRI and 11C-PE2I PET imaging study, 4th Congress of the European-Academy-of-Neurology (EAN), Publisher: WILEY, Pages: 345-345, ISSN: 1351-5101
Martin-Bastida A, Lao-Kaim NP, Xing Y, et al., 2017, NIGRAL IRON SUSCEPTIBILITY IN PARKINSON'S DISEASE: A LONGITUDINAL STUDY, Publisher: BMJ PUBLISHING GROUP, Pages: A34-A35, ISSN: 0022-3050
Li W, Lao-Kaim N, Roussakis AA, et al., 2017, 11C-PE2I and 18F-DOPA PET for assessing progression rate in Parkinson’s: a longitudinal study, Movement Disorders, Vol: 33, Pages: 117-127, ISSN: 0885-3185
Background18F-dopa PET measuring aromatic l-amino acid decarboxylase activity is regarded as the gold standard for evaluating dopaminergic function in Parkinson's disease. Radioligands for dopamine transporters are also used in clinical trials and for confirming PD diagnosis. Currently, it is not clear which imaging marker is more reliable for assessing clinical severity and rate of progression. The objective of this study was to directly compare 18F-dopa with the highly selective dopamine transporter radioligand 11C-PE2I for the assessment of motor severity and rate of progression in PD.MethodsThirty-three mild-moderate PD patients underwent 18F-dopa and 11C-PE2I PET at baseline. Twenty-three were followed up for 18.8 ± 3.4 months.ResultsStandard multiple regression at baseline indicated that 11C-PE2I BPND predicted UPDRS-III and bradykinesia-rigidity scores (P < 0.05), whereas 18F-dopa Ki did not make significant unique explanatory contributions. Voxel-wise analysis showed negative correlations between 11C-PE2I BPND and motor severity across the whole striatum bilaterally. 18F-Dopa Ki clusters were restricted to the most affected putamen and caudate. Longitudinally, negative correlations were found between striatal Δ11C-PE2I BPND, ΔUPDRS-III, and Δbradykinesia-rigidity, whereas no significant associations were found for Δ18F-dopa Ki. One cluster in the most affected putamen was identified in the longitudinal voxel-wise analysis showing a negative relationship between Δ11C-PE2I BPND and Δbradykinesia-rigidity.ConclusionsStriatal 11C-PE2I appears to show greater sensitivity for detecting differences in motor severity than 18F-dopa. Furthermore, dopamine transporter decline is closely associated with motor progression over time, whereas no such relationship was found with aromatic l-amino acid decarboxylase. 11C-PE2I may be more effective for evaluating the efficacy of neuroprotective treatments in PD. © 2017 Interna
Roussakis AA, Towey D, Piccini P, 2017, Longitudinal single-photon emitted computed tomography (SPECT) study of striatal dopamine transporter (DAT) density: Relevance to levodopa-induced dyskinesias in Parkinson's disease, 23rd World Congress of Neurology (WCN), Publisher: ELSEVIER SCIENCE BV, Pages: 949-949, ISSN: 0022-510X
Li W, Lao-Kaim NP, Roussakis A, et al., 2017, Longitudinal comparison of 11C-PE2I and 18F-DOPA pet for assessing severity and rate of disease progression in patients with Parkinson's disease, 23rd World Congress of Neurology (WCN), Publisher: ELSEVIER SCIENCE BV, Pages: 128-128, ISSN: 0022-510X
Roussakis A-A, Towey D, Piccini P, 2017, Changes over time in striatal DAT availability in Parkinson's disease: Relevance to levodopa-induced dyskinesias, 3rd Congress of the European-Academy-of-Neurology, Publisher: WILEY, Pages: 661-661, ISSN: 1351-5101
Bastida AM, Lao-Kaim NP, Xing Y, et al., 2017, Assessing longitudinal iron deposition in deep grey matter nuclei with high-pass filtered phase MR Imaging in Parkinson's disease, 3rd Congress of the European-Academy-of-Neurology, Publisher: WILEY, Pages: 427-427, ISSN: 1351-5101
Bastida AM, Xing Y, Pietracupa S, et al., 2017, Resting state nigral functional connectivity in Parkinson's disease: A cross-sectional study, 3rd Congress of the European-Academy-of-Neurology, Publisher: WILEY, Pages: 428-428, ISSN: 1351-5101
Li W, Lao-Kaim N, Roussakis A, et al., 2017, 11C-PE2I and 18F-DOPA PET imaging for assessing the severity and rate of progression in Parkinson's disease: The longitudinal study, 3rd Congress of the European-Academy-of-Neurology, Publisher: WILEY, Pages: 593-593, ISSN: 1351-5101
Roussakis AA, Towey D, Piccini P, 2017, SPECT imaging of striatal DAT availability in Parkinson's disease: Changes over time and relevance to dyskinesias, 21st International Congress of Parkinson's Disease and Movement Disorders, Publisher: WILEY, ISSN: 0885-3185
Roussakis AA, Lao-Kaim N, Martin-Bastida A, et al., 2017, Serotonin-to-dopamine transporter ratios in Parkinson's dyskinesias: The longitudinal study, 21st International Congress of Parkinson's Disease and Movement Disorders, Publisher: WILEY, ISSN: 0885-3185
Li W, Lao-Kaim N, Roussakis A-A, et al., 2017, Longitudinal comparison of 11C-PE2I and 18F-DOPA PET for assessing severity and rate of disease progression in patients with Parkinson's disease, 21st International Congress of Parkinson's Disease and Movement Disorders, Publisher: WILEY, ISSN: 0885-3185
Martin-Bastida A, Xing Y, Pietracupa S, et al., 2017, Assessing Nigral Functional Connectivity in Parkinson's disease With Resting State Functional MRI, 21st International Congress of Parkinson's Disease and Movement Disorders, Publisher: WILEY, ISSN: 0885-3185
Martin-Bastida A, Lao-Kaim N, Xing Y, et al., 2017, High-Pass Filtered Phase Mr Imaging to Detect Longitudinal Motor Associations of Iron Accumulation in Parkinson's Disease, 21st International Congress of Parkinson's Disease and Movement Disorders, Publisher: WILEY, ISSN: 0885-3185
Martin-Bastida A, Lao-Kaim NP, Loane C, et al., 2016, Motor associations of iron accumulation in deep grey matter nuclei in Parkinson's disease: a cross-sectional study of iron-related magnetic resonance imaging susceptibility., European Journal of Neurology, Vol: 24, Pages: 357-365, ISSN: 1468-1331
BACKGROUND AND PURPOSE: To determine whether iron deposition in deep brain nuclei assessed using high-pass filtered phase imaging plays a role in motor disease severity in Parkinson's disease (PD). METHODS: Seventy patients with mild to moderate PD and 20 age- and gender-matched healthy volunteers (HVs) underwent susceptibility-weighted imaging on a 3 T magnetic resonance imaging scanner. Phase shifts (radians) in deep brain nuclei were derived from high-pass filtered phase images and compared between groups. Analysis of clinical laterality and correlations with motor severity (Unified Parkinson's Disease Rating Scale, Part III, UPDRS-III) were performed. Phase shifts (in radians) were compared between HVs and three PD subgroups divided according to UPDRS-III scores using analysis of covariance, adjusting for age and regional area. RESULTS: Parkinson's disease patients had significantly (P < 0.001) higher radians than HVs bilaterally in the putamen, globus pallidus and substantia nigra (SN). The SN contralateral to the most affected side showed higher radians (P < 0.001) compared to the less affected side. SN radians positively correlated with UPDRS-III and bradykinesia-rigidity subscores, but not with tremor subscores. ancova followed by post hoc Bonferroni-adjusted pairwise comparisons revealed that SN radians were significantly greater in the PD subgroup with higher UPDRS-III scores compared to both lowest UPDRS-III PD and HV groups (P < 0.001). CONCLUSIONS: Increased nigral iron accumulation in PD appears to be stratified according to disease motor severity and correlates with symptoms related to dopaminergic neurodegeneration. This semi-quantitative in vivo iron assessment could prove useful for objectively monitoring PD progression, especially in clinical trials concerning iron chelation therapies.
Rolinski M, Griffanti L, Piccini P, et al., 2016, Basal ganglia dysfunction in idiopathic REM sleep behaviour disorder parallels that in early Parkinson’s disease, Brain, Vol: 139, Pages: 2224-2234, ISSN: 0006-8950
Resting-state fMRI (rs-fMRI) dysfunction within the basal ganglia network (BGN) is a feature of early Parkinson’s disease (Szewczyk-Krolikowski et al., 2014, Rolinski et al., 2015), and may be a diagnostic biomarker of basal ganglia dysfunction. Currently, it is unclear whether these changes are present in so-called idiopathic rapid eye movement sleep behaviour disorder (RBD), a condition associated with a high rate of future conversion to Parkinson’s. In this study, we explore the utility of rs-fMRI to detect BGN dysfunction in RBD. We compare these data to a set of healthy controls, and to a set of patients with established early Parkinson’s. Furthermore, we explore the relationship between rs-fMRI BGN dysfunction and loss of dopaminergic neurons assessed with dopamine transporter single photon emission computerised tomography (SPECT), and perform morphometric analyses to assess grey matter loss.26 patients with polysomnographically established RBD, 48 Parkinson’s patients and 23 healthy controls were included in this study. Resting-state networks were isolated from task-free fMRI data using dual regression with a template was derived from a separate cohort of 80 elderly HC participants. Rs-fMRI parameter estimates were extracted from the study subjects in the BGN. In addition, 8 RBD, 10 Parkinson’s and 10 control subjects received 123I-ioflupane SPECT. We tested for reduction of BGN connectivity, and for loss of tracer uptake in RBD and Parkinson’s relative to each other and to controls. Connectivity measures of BGN network dysfunction differentiated both RBD and Parkinson’s from controls with high sensitivity (96%) and specificity (74% for RBD, 78% for PD), indicating its potential as an indicator of early basal ganglia dysfunction. RBD was indistinguishable from Parkinson’s on rs-fMRI despite obvious differences on dopamine transported SPECT. Basal ganglia connectivity is a promising biomarker for the detection of
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