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      The Role of Vitamin D in Disease Progression in Early Parkinson’s Disease

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          Abstract

          Background:

          Previous cross-sectional studies have shown that Parkinson’s disease (PD) patients have lower serum 25-hydroxy vitamin D (25(OH)D) concentrations than controls. Vitamin D deficiency was associated with increased disease severity and cognitive impairment in prevalent PD patients.

          Objective:

          The aim of the study was to determine 25(OH)D in newly diagnosed PD and age-matched controls and to assess if there was an association with clinical outcomes (disease severity, cognition and falls) over the 36-month follow up period.

          Methods:

          A prospective observational study of newly diagnosed PD patients in the North East of England with age-matched controls (PD, n = 145; control, n = 94). Serum 25(OH)D was assessed at baseline and 18 months. Participants underwent clinical assessment at baseline, 18 and 36 months. One hundred and ten participants with PD also took part in a prospective falls study.

          Results:

          Mean serum 25(OH)D concentrations were lower in PD than control participants at baseline (44.1±21.7 vs. 52.2±22.1 nmol/L, p < 0.05) and 18 months (44.2±23.6 vs. 55.7±28.8 nmol/L, p < 0.05). Baseline serum 25(OH)D concentration, age, motor score and dosage of dopaminergic medication were significant predictors of variance of motor severity at 36 months (( ΔR 2 = 0.039, F = 6.6, p < 0.01). Serum 25(OH)D was not associated with cognition or falls during the follow up period.

          Conclusions:

          Patients with incident PD had significantly lower serum 25(OH)D concentrations than age-matched controls, which may have implications in terms of bone health and fracture risk. There was a small but significant association between vitamin D status at baseline and disease motor severity at 36 months.

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          Most cited references23

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          Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases.

          Few detailed clinico-pathological correlations of Parkinson's disease have been published. The pathological findings in 100 patients diagnosed prospectively by a group of consultant neurologists as having idiopathic Parkinson's disease are reported. Seventy six had nigral Lewy bodies, and in all of these Lewy bodies were also found in the cerebral cortex. In 24 cases without Lewy bodies, diagnoses included progressive supranuclear palsy, multiple system atrophy, Alzheimer's disease, Alzheimer-type pathology, and basal ganglia vascular disease. The retrospective application of recommended diagnostic criteria improved the diagnostic accuracy to 82%. These observations call into question current concepts of Parkinson's disease as a single distinct morbid entity.
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            Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain.

            Despite a growing body of evidence that Vitamin D is involved in mammalian brain functioning, there has been a lack of direct evidence about its role in the human brain. This paper reports, for the first time, the distribution of the 1,25-dihydroxyvitamin D3 receptor (VDR), and 1alpha-hydroxylase (1alpha-OHase), the enzyme responsible for the formation of the active vitamin in the human brain. The receptor and the enzyme were found in both neurons and glial cells in a regional and layer-specific pattern. The VDR was restricted to the nucleus whilst 1alpha-OHase was distributed throughout the cytoplasm. The distribution of the VDR in human brain was strikingly similar to that reported in rodents. Many regions contained equivalent amounts of both the VDR and 1alpha-OHase, however the macrocellular cells within the nucleus basalis of Meynert (NBM) and the Purkinje cells in the cerebellum expressed 1alpha-OHase in the absence of VDR. The strongest immunohistochemical staining for both the receptor and enzyme was in the hypothalamus and in the large (presumably dopaminergic) neurons within the substantia nigra. The observed distribution of the VDR is consistent with the proposal that Vitamin D operates in a similar fashion to the known neurosteroids. The widespread distribution of 1alpha-OHase and the VDR suggests that Vitamin D may have autocrine/paracrine properties in the human brain.
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              Characterizing mild cognitive impairment in incident Parkinson disease: the ICICLE-PD study.

              To describe the frequency of mild cognitive impairment (MCI) in Parkinson disease (PD) in a cohort of newly diagnosed incident PD cases and the associations with a panel of biomarkers. Between June 2009 and December 2011, 219 subjects with PD and 99 age-matched controls participated in clinical and neuropsychological assessments as part of a longitudinal observational study. Consenting individuals underwent structural MRI, lumbar puncture, and genotyping for common variants of COMT, MAPT, SNCA, BuChE, EGF, and APOE. PD-MCI was defined with reference to the new Movement Disorder Society criteria. The frequency of PD-MCI was 42.5% using level 2 criteria at 1.5 SDs below normative values. Memory impairment was the most common domain affected, with 15.1% impaired at 1.5 SDs. Depression scores were significantly higher in those with PD-MCI than the cognitively normal PD group. A significant correlation was found between visual Pattern Recognition Memory and cerebrospinal β-amyloid 1-42 levels (β standardized coefficient = 0.350; p = 0.008) after controlling for age and education in a linear regression model, with lower β-amyloid 1-42 and 1-40 levels observed in those with PD-MCI. Voxel-based morphometry did not reveal any areas of significant gray matter loss in participants with PD-MCI compared with controls, and no specific genotype was associated with PD-MCI at the 1.5-SD threshold. In a large cohort of newly diagnosed PD participants, PD-MCI is common and significantly correlates with lower cerebrospinal β-amyloid 1-42 and 1-40 levels. Future longitudinal studies should enable us to determine those measures predictive of cognitive decline.
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                Author and article information

                Journal
                J Parkinsons Dis
                J Parkinsons Dis
                JPD
                Journal of Parkinson's Disease
                IOS Press (Nieuwe Hemweg 6B, 1013 BG Amsterdam, The Netherlands )
                1877-7171
                1877-718X
                4 October 2017
                1 November 2017
                2017
                : 7
                : 4
                : 669-675
                Affiliations
                [a ]Clinical Ageing Research Unit, Newcastle University , Campus for Ageing and Vitality, Newcastle upon Tyne, UK
                [b ]Bone Clinic, Freeman Hospital , Freeman Road, Newcastle upon Tyne, UK
                [c ]Industrial Statistics Research Unit, Herschel Building, Newcastle University , Newcastle upon Tyne, UK
                [d ]Department of Geriatric Medicine, University of Edinburgh , Edinburgh, UK
                [e ]School of Medicine and Menzies Health Institute Queensland, Griffith University , QLD, Australia
                [f ]Department of Medicine, Faculty of Medicine and Health Sciences, University of East Anglia , Norwich Research Park, Norwich, UK
                [g ]MRC Human Nutrition Research, Cambridge, UK
                [h ]Institute of Neuroscience, Newcastle University , Clinical Ageing Research Unit, Campus for Ageing and Vitality, UK
                [i ]Institute of Neuroscience, The Medical School, Newcastle University , UK
                Author notes
                [* ]Correspondence to: Dr. Isobel Sleeman, Clinical Ageing Research Unit, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5LP, UK. Tel.: +44 191 2081250; Fax: +44 191 2826043; E-mail: isobel.sleeman@ 123456ncl.ac.uk .
                Article
                JPD171122
                10.3233/JPD-171122
                5676984
                28984616
                43b45f1a-f12c-482c-ae13-f805928e2b5d
                © 2017 – IOS Press and the authors. All rights reserved

                This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY 4.0) License.

                History
                : 11 September 2017
                Categories
                Research Report

                balance,cognition,disease progression,fall,25-hydroxy vitamin d,parkinson’s disease,vitamin d

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