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      Vascular disease and vascular risk factors in relation to motor features and cognition in early Parkinson's disease

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          ABSTRACT

          Objective

          The purpose of this study was to examine the relationship between vascular disease (and vascular risk factors), cognition and motor phenotype in Parkinson's disease (PD).

          Methods

          Recently diagnosed PD cases were enrolled in a multicenter prospective observational longitudinal cohort study. Montreal cognitive assessment (normal >23, mild cognitive impairment 22 to 23 or lower but without functional impairment, and dementia 21 or less with functional impairment) and Movement Disorder Society Unified PD Rating Scale part 3 (UPDRS 3) scores were analyzed in relation to a history of vascular events and risk factors.

          Results

          In 1759 PD cases, mean age 67.5 (standard deviation 9.3) years, mean disease duration 1.3 (standard deviation 0.9) years, 65.2% were men, 4.7% had a history of prior stroke or transient ischemic attack, and 12.5% had cardiac disease (angina, myocardial infarction, heart failure). In cases without a history of vascular disease, hypertension was recorded in 30.4%, high cholesterol 27.3%, obesity 20.7%, diabetes 7.2%, and cigarette smoking in 4.6%. Patients with prior stroke or transient ischemic attack were more likely to have cognitive impairment (42% vs 25%) and postural instability gait difficulty (53.5% vs 39.5%), but these findings were not significant after adjustment for age, sex, and disease duration ( P = .075). The presence of more than 2 vascular risks was associated with worse UPDRS 3 motor scores (beta coefficient 4.05, 95% confidence interval 1.48, 6.61, p = .002) and with cognitive impairment (ordinal odds ratio 2.24, 95% confidence interval 1.34, 3.74, p = .002). In 842 patients (47.8%) with structural brain imaging, white matter leukoaraiosis, but not lacunar or territorial infarction, was associated with impaired cognition ( p = .006) and postural instability gait difficulty ( p = .010).

          Conclusion

          Vascular comorbidity is significantly associated with cognitive and gait impairment in patients with early PD, which may have prognostic and treatment implications. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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          Most cited references28

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          Prospective assessment of falls in Parkinson's disease.

          We studied prospectively the epidemiology, clinical impact and prediction of falls in 59 moderately affected patients with Parkinson's disease (PD) (mean UPDRS motor score 31.5; mean age 61 years) and 55 controls (mean age 60 years). At baseline, balance and gait were evaluated extensively. The retropulsion test (response to sudden shoulder pull) was executed first unexpectedly and five more times following prior warning. All persons used standardised scoring forms to document their falls during six months. Thirty patients (50.8 %) and eight controls (14.5%) fell at least once (relative risk [RR] 6.1; 95% confidence interval [CI] 2.5-15.1, p or = 2) falls occurred in 15 patients (25.4%), but in only two controls (RR 9.0; 95 % CI 2.0-41.7; p=0.001). Recurrent falls were more common among persons taking benzodiazepines (RR 5.0; 95% CI 1.6-15.5; p 100; 95% CI 3.1-585) and asking for prior falls (RR 5.0; 95% CI 1.2-20.9). We conclude that falls are common and disabling, even in relatively early stage PD. Recurrent fallers were best predicted by disease severity and presence of prior falls. Strategies to prevent falls in PD should particularly focus at intrinsic (patient-related) factors, such as minimising the use of benzodiazepines.
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            Improved accuracy of clinical diagnosis of Lewy body Parkinson's disease.

            The authors studied the accuracy of clinical diagnosis of idiopathic PD (IPD) in 100 consecutive clinically diagnosed cases that came to neuropathological examination. Ninety fulfilled pathologic criteria for IPD. Ten were misdiagnosed: multiple system atrophy (six), progressive supranuclear palsy (two), post-encephalitic parkinsonism (one), and vascular parkinsonism (one). Assessment of the clinical features suggests that an accuracy of 90% may be the highest that can be expected using current diagnostic criteria.
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              The natural history of treated Parkinson's disease in an incident, community based cohort.

              Our understanding of the natural history of idiopathic Parkinson's disease (PD) remains limited. In the era of potential disease modifying therapies, there is an urgent need for studies assessing the natural evolution of treated PD from onset so that relevant outcome measures can be identified for clinical trials. No previous studies have charted progression in unselected patients followed from the point of diagnosis. A representative cohort of 132 PD patients was followed from diagnosis for up to 7.9 years (mean 5.2 years). Comprehensive clinical and neuropsychological evaluations were performed every 18 months. Disease progression was evaluated using well validated clinical measures (motor progression and development of dyskinesia on the Unified PD Rating Scale and Hoehn-Yahr scale, dementia onset according to DSM-IV criteria). Multi-level linear modelling was used to chart the nature and rate of progression in parkinsonian symptoms and signs over time. The prognostic importance of baseline demogr‘aphic, clinical and genetic variables was evaluated using survival analysis. Axial (gait and postural) symptoms evolve more rapidly than other motor features of PD and appear to be the best index of disease progression. Conversely, conventional outcome measures are relatively insensitive to change over time. Earlier onset of postural instability (Hoehn-Yahr stage 3) is strongly associated with increased age at disease onset and has a significant impact on quality of life. Dementia risk is associated with increased age, impaired baseline semantic fluency and the MAPT H1/H1 genotype. The efficacy of disease modifying therapies may be more meaningfully assessed in terms of their effects in delaying the major milestones of PD, such as postural instability and dementia, since it is these that have the greatest impact on patients.
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                Author and article information

                Contributors
                nmalek@nhs.net
                Journal
                Mov Disord
                Mov. Disord
                10.1002/(ISSN)1531-8257
                MDS
                Movement Disorders
                John Wiley and Sons Inc. (Hoboken )
                0885-3185
                1531-8257
                06 October 2016
                October 2016
                : 31
                : 10 ( doiID: 10.1002/mds.v31.10 )
                : 1518-1526
                Affiliations
                [ 1 ] Department of Neurology, Institute of Neurological SciencesQueen Elizabeth University Hospital GlasgowUnited Kingdom
                [ 2 ] School of Social and Community MedicineUniversity of Bristol BristolUnited Kingdom
                [ 3 ] Institute of NeuroscienceUniversity of Newcastle Newcastle upon TyneUnited Kingdom
                [ 4 ] Department of NeurologyQueen's Medical Centre NottinghamUnited Kingdom
                [ 5 ] Department of Clinical NeurosciencesJohn van Geest Centre for Brain Repair CambridgeUnited Kingdom
                [ 6 ] Reta Lila Weston Laboratories, Department of Molecular NeuroscienceUCL Institute of Neurology LondonUnited Kingdom
                [ 7 ] Department of Clinical NeuroscienceUCL Institute of Neurology LondonUnited Kingdom
                [ 8 ] Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics Cardiff University CardiffUnited Kingdom
                [ 9 ] Department of Molecular NeuroscienceUCL Institute of Neurology LondonUnited Kingdom
                Author notes
                [*] [* ] Correspondence to: Dr. Naveed Malek, Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow G51 4TF; nmalek@ 123456nhs.net
                Article
                MDS26698
                10.1002/mds.26698
                5082556
                27324570
                0ad3d9a5-6cfa-44c6-9c87-0c8fb9b2444b
                © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 09 December 2015
                : 12 May 2016
                : 15 May 2016
                Page count
                Figures: 1, Tables: 5, Pages: 9, Words: 5733
                Funding
                Funded by: Parkinson's UK
                Funded by: National Institute for Health Research (NIHR) DeNDRoN network
                Funded by: NIHR Newcastle Biomedical Research Unit
                Funded by: Newcastle University
                Funded by: NIHR funded Biomedical Research Centre in Cambridge
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                mds26698
                October 2016
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.9.6 mode:remove_FC converted:27.10.2016

                Medicine
                parkinson's disease,gender,phenotype,diabetes,cerebrovascular
                Medicine
                parkinson's disease, gender, phenotype, diabetes, cerebrovascular

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