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Early predictors of mortality in parkinsonism and Parkinson disease: A population-based study
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
Umeå University, Faculty of Social Sciences, Department of Psychology. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
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2018 (English)In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 91, no 22, p. E2045-E2056Article in journal (Refereed) Published
Abstract [en]

Objective To examine mortality and associated risk factors, including possible effects of mild cognitive impairment, imaging, and CSF abnormalities, in a community-based population with incident parkinsonism and Parkinson disease. Methods One hundred eighty-two patients with new-onset, idiopathic parkinsonism were diagnosed from January 2004 through April 2009, in a catchment area of 142,000 inhabitants in Sweden. Patients were comprehensively investigated according to a multimodal research protocol and followed prospectively for up to 13.5 years. A total of 109 patients died. Mortality rates in the general Swedish population were used to calculate standardized mortality ratio and expected survival, and Cox proportional hazard models were used to investigate independent predictors of mortality. Results The standardized mortality ratio for all patients was 1.84 (95% confidence interval 1.50-2.22, p < 0.001). Patients with atypical parkinsonism (multiple system atrophy or progressive supranuclear palsy) had the highest mortality. In early Parkinson disease, a mild cognitive impairment diagnosis, freezing of gait, hyposmia, reduced dopamine transporter activity in the caudate, and elevated leukocytes in the CSF were significantly associated with shorter survival. Conclusion Although patients presenting with idiopathic parkinsonism have reduced survival, the survival is highly dependent on the type and characteristics of the parkinsonian disorder. Patients with Parkinson disease presenting with normal cognitive function seem to have a largely normal life expectancy. The finding of a subtle CSF leukocytosis in patients with Parkinson disease with short survival may have clinical implications.

Place, publisher, year, edition, pages
Wolters Kluwer, 2018. Vol. 91, no 22, p. E2045-E2056
National Category
Neurology
Identifiers
URN: urn:nbn:se:umu:diva-154849DOI: 10.1212/WNL.0000000000006576ISI: 000452519500002PubMedID: 30381367OAI: oai:DiVA.org:umu-154849DiVA, id: diva2:1275140
Available from: 2019-01-04 Created: 2019-01-04 Last updated: 2019-05-07Bibliographically approved
In thesis
1. The biology of cognitive decline and reduced survival in Parkinson disease: prognostic factors in a population-based cohort
Open this publication in new window or tab >>The biology of cognitive decline and reduced survival in Parkinson disease: prognostic factors in a population-based cohort
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Parkinson disease (PD) is a progressive neurodegenerative disease that affects about 1% of the population over 60 years. The cardinal symptoms are motor disabilities but cognitive decline is also common. About 50% of all persons with PD develop dementia within 10 years after disease onset. Dementia in PD account for high social costs and has large, negative effects on quality of life. 

Aims. The aim of the study was to investigate clinical, neurobiological and genetic factors of importance for progression and for the prognosis in PD and parkinsonism. First, we aimed to describe mortality and risk factors for death, including possible associations with cognitive dysfunction, in patients with idiopathic parkinsonism. Second, we aimed to study if biomarkers in the cerebrospinal fluid (CSF) are useful for the diagnosis of different forms of idiopathic parkinsonism and prediction of cognitive decline in PD. 

Methods. A population-based cohort consisting of patients with new-onset, idiopathic parkinsonism was studied prospectively. After screening in a catchment area of ~142 000 inhabitants in Sweden, 182 patients with parkinsonism were included. The patients were investigated comprehensively, including neuropsychological testing, multimodal neuroimaging and genetic and biosample analyses. During follow up, 143 patients were diagnosed with PD, 13 with multiple system atrophy (MSA), and 18 with progressive supranuclear palsy (PSP). A total of 109 patients died. 

Results. Patients with MSA and PSP had the shortest life expectancy. PD patients who presented with normal cognitive function had a largely normal life expectancy. In contrast, the mortality was increased in PD patients with cognitive impairment, freezing of gait, hyposmia, and mildly elevated leukocytes in the CSF. Of importance for the prognosis, patients with PD with an early CSF pattern of high Neurofilament light protein, low β-amyloid, and high heart fatty acid binding protein had an 11.8 times increased risk of developing PD dementia (95% CI 3.3-42.1, p <0.001), compared with PD patients with a more ”normal” CSF pattern. Variation in genes associated with dopamine function was also associated with some effects on cognitive functions in PD. 

Conclusions. PD subtypes, for instance the subtype characterized by cognitive decline, have distinguishing clinical, neurochemical and neurobiological traits, which are of importance for the prognosis and the survival. An early CSF analysis is useful for predicting cognitive decline. The finding of a low-grade immune reaction in the CSF of patients with PD may have clinical implications. In clinical practice, CSF biomarkers could be useful for improving diagnosis and prognostication.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2019. p. 67
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 2006
Keywords
Parkinson disease, multiple system atrophy, progressive supranuclear palsy, natural history, cognitive impairment, dementia, predictors of mortality, cerebrospinal fluid biomarkers, prospective, population-based
National Category
Neurosciences
Research subject
Neurology
Identifiers
urn:nbn:se:umu:diva-155588 (URN)978-91-7855-022-7 (ISBN)
Public defence
2019-02-15, Sal D, byggnad 1D, våning 9, Norrlands universitetssjukhus, Umeå, 13:00 (Swedish)
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Available from: 2019-01-25 Created: 2019-01-23 Last updated: 2019-01-24Bibliographically approved

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Bäckström, DavidGranåsen, GabrielEriksson Domellöf, MagdalenaxLinder, JanJakobson Mo, SusannaRiklund, KatrineForsgren, Lars

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