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      Patterns of grey matter loss associated with motor subscores in early Parkinson's disease

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          Abstract

          Classical motor symptoms of Parkinson's disease (PD) such as tremor, rigidity, bradykinesia, and axial symptoms are graded in the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III. It is yet to be ascertained whether parkinsonian motor symptoms are associated with different anatomical patterns of neurodegeneration as reflected by brain grey matter (GM) alteration. This study aimed to investigate associations between motor subscores and brain GM at voxel level. High resolution structural MRI T1 scans from the Parkinson's Progression Markers Initiative (PPMI) repository were employed to estimate brain GM intensity of PD subjects. Correlations between GM intensity and total MDS-UPDRS III and its four subscores were computed. The total MDS-UPDRS III score was significantly negatively correlated bilaterally with putamen and caudate GM density. Lower anterior striatal GM intensity was significantly associated with higher rigidity subscores, whereas left-sided anterior striatal and precentral cortical GM reduction were correlated with severity of axial symptoms. No significant morphometric associations were demonstrated for tremor subscores. In conclusion, we provide evidence for neuroanatomical patterns underpinning motor symptoms in early PD.

          Highlights

          • MDS-UPDRS III score is inversely correlated with putamen and caudate grey matter intensity in patients with early Parkinson's disease (PD).

          • Motor subscores reveal partially overlapping patterns of negative correlation with grey matter intensity for rigidity and axial symptoms.

          • These findings point to early anterior striatal grey matter reduction underpinning the development of rigidity.

          • Tremor scores are unrelated to grey mater morphometric changes.

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          Most cited references33

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          Variable expression of Parkinson's disease: a base-line analysis of the DATATOP cohort. The Parkinson Study Group.

          The DATATOP database, which includes clinical information on 800 patients with early untreated Parkinson's disease (PD), is well suited to explore clinical heterogeneity in PD. Patients with early-onset PD (less than or equal to 40 years, N = 33) reached the same level of disability as the late-onset PD (greater than or equal to 70 years, N = 85) group at a significantly slower rate (2.9 vs. 1.7 years). Early-onset PD patients functioned cognitively better than late-onset PD patients. Bradykinesia, and postural instability and gait difficulty (PIGD), were more common at onset in patients with a rapid rate of disease progression ("malignant PD"; duration of symptoms less than 1 year and Hoehn/Yahr stage of 2.5, N = 11) as compared with those with a relatively slow rate of progression ("benign PD"; duration of symptoms greater than 4 years, N = 65). Comparisons of tremor-dominant PD (mean tremor score/mean PIGD score less than or equal to 1.5, N = 441) with the PIGD-dominant type (mean tremor score/mean PIGD score greater than or equal to 1.0, N = 233) provided support for the existence of clinical subtypes. The PIGD group reported significantly greater subjective intellectual, motor, and occupational impairment than the tremor group. Stage II patients had higher depression scores than stage I patients. Among the patients participating in the DATATOP, older age at onset with bradykinesia, or with the PIGD form of PD, is associated with more functional disability than when the symptoms are dominated by tremor or begin at a younger age.
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            Cerebral atrophy in Parkinson's disease with and without dementia: a comparison with Alzheimer's disease, dementia with Lewy bodies and controls.

            Parkinson's disease is a common neurodegenerative disorder primarily characterized by rigidity, tremor and bradykinesia. Cognitive impairment and neuropsychiatric symptoms are frequent in Parkinson's disease, with a 70% cumulative incidence of dementia. The aim of this cross-sectional study was to establish the pattern of cerebral atrophy on MRI in Parkinson's disease patients with dementia. We used voxel-based morphometry (VBM) to provide an unbiased means of investigating brain volume loss. Whole brain structural T1-weighted MRI scans from Parkinson's disease patients with dementia (PDD, n = 26), Parkinson's disease patients without dementia (n = 31), Alzheimer's disease patients (n = 28), patients with dementia with Lewy bodies (DLB, n = 17) and control subjects (n = 36) were acquired. Images were analysed using SPM99 and the optimized method of VBM. Reduced grey matter volume in PDD patients compared with controls was observed bilaterally in the temporal lobe, including the hippocampus and parahippocampal gyrus, and in the occipital lobe, the right frontal lobe and the left parietal lobe, as well as some subcortical regions. Parkinson's disease patients without dementia showed reduced grey matter volume in the frontal lobe compared with control subjects. There was significant grey matter atrophy bilaterally in the occipital lobe of PDD patients compared with Parkinson's disease patients. In addition, significant temporal lobe atrophy, including the hippocampus and parahippocampal gyrus was detected in Alzheimer's disease relative to PDD. No significant volumetric differences were observed in PDD compared with DLB. Thus, Parkinson's disease involves grey matter loss in frontal areas. In PDD, this extends to temporal, occipital and subcortical areas, with occipital atrophy in PDD being the only difference between the two groups. This provides important information about the pattern of cerebral atrophy in Parkinson's disease and PDD.
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              Diffusion tensor imaging in parkinsonian syndromes: a systematic review and meta-analysis.

              We performed a systematic review to assess alterations in measures of diffusion tensor imaging (DTI) in parkinsonian syndromes, exploring the potential role of DTI in diagnosis and as a candidate biomarker. We searched EMBASE and Medline databases for DTI studies comparing parkinsonian syndromes or related dementias with controls or another defined parkinsonian syndrome. Key details for each study regarding participants, imaging methods, and results were extracted. Estimates were pooled, where appropriate, by random-effects meta-analysis. Of 333 results, we identified 43 studies suitable for inclusion (958 patients, 764 controls). DTI measures detected alterations in all parkinsonian syndromes, with distribution varying differentially with disease type. Nine studies were included in a meta-analysis of the substantia nigra in Parkinson disease. A notable effect size was found for lowered fractional anisotropy in the substantia nigra for patients with Parkinson disease vs controls (-0.639, 95% confidence interval -0.860 to -0.417, p < 0.0001). DTI may be a promising biomarker in parkinsonian syndromes and have a future role in differential diagnosis. Larger cohort studies are required to investigate some encouraging preliminary findings. Given the complexity of the parkinsonian syndromes, it is likely that any potential DTI biomarker would be used in combination with other relevant biomarkers.
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                Author and article information

                Contributors
                Journal
                Neuroimage Clin
                Neuroimage Clin
                NeuroImage : Clinical
                Elsevier
                2213-1582
                10 November 2017
                2018
                10 November 2017
                : 17
                : 498-504
                Affiliations
                [a ]Radiological Sciences, Division of Clinical Neuroscience, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK
                [b ]Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham, Nottingham NG7 2UH, UK
                [c ]NIHR Nottingham Biomedical Research Centre, Nottingham NG7 2UH, UK
                [d ]Centre for Neurodegeneration and Neuroinflammation, Division of Brain Sciences, Imperial College London, London W12 0NN, UK
                Author notes
                [* ]Corresponding authors at: Radiological Sciences, Division of Clinical Neuroscience, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK.Radiological SciencesDivision of Clinical NeuroscienceUniversity of NottinghamQueen's Medical CentreNottinghamNG7 2UHUK Xingfeng.Li@ 123456gmail.com Dorothee.Auer@ 123456nottingham.ac.uk
                Article
                S2213-1582(17)30289-9
                10.1016/j.nicl.2017.11.009
                5700824
                29201638
                992657ec-a608-4727-b2de-521383ba67ff
                © 2017 The Authors

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 24 February 2017
                : 13 September 2017
                : 8 November 2017
                Categories
                Regular Article

                parkinson's disease,mds-updrs iii,motor symptoms,mri grey matter,pd subtypes

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