umu.sePublikationer
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Cerebrospinal Fluid Patterns and the Risk of Future Dementia in Early, Incident Parkinson Disease
Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
Visa övriga samt affilieringar
2015 (Engelska)Ingår i: JAMA Neurology, ISSN 2168-6149, E-ISSN 2168-6157, Vol. 72, nr 10, s. 1175-1182Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

IMPORTANCE: Alterations in cerebrospinal fluid (CSF) have been found in Parkinson disease (PD) and in PD dementia (PDD), but the prognostic importance of such changes is not well known. In vivo biomarkers for disease processes in PD are important for future development of disease-modifying therapies. OBJECTIVE: To assess the diagnostic and prognostic value of a panel of CSF biomarkers in patients with early PD and related disorders. DESIGN, SETTING, AND PARTICIPANTS: Regional population-based, prospective cohort study of idiopathic parkinsonism that included patients diagnosed between January 1, 2004, and April 30, 2009, by amovement disorder team at a university hospital that represented the only neurology clinic in the region. Participants were 128 nondemented patients with new-onset parkinsonism (104 with PD, 11 with multiple system atrophy, and 13 with progressive supranuclear palsy) who were followed up for 5 to 9 years. At baseline, CSF from 30 healthy control participants was obtained for comparison. MAIN OUTCOMES AND MEASURES: Cerebrospinal fluid concentrations of neurofilament light chain protein, Aβ1-42, total tau, phosphorylated tau, α-synuclein, and heart fatty acid-binding protein were quantified by 2 blinded measurements (at baseline and after 1 year). Follow-up included an extensive neuropsychological assessment. As PD outcome variables, mild cognitive impairment and incident PDD were diagnosed based on published criteria. RESULTS: Among the 128 study participants, the 104 patients with early PD had a different CSF pattern compared with the 13 patients with progressive supranuclear palsy (baseline area under the receiver operating characteristic curve, 0.87; P < .0001) and the 30 control participants (baseline area under the receiver operating characteristic curve, 0.69; P = .0021). A CSF biomarker pattern associated with the development of PDD was observed. In PD, high neurofilament light chain protein, low Aβ1-42, and high heart fatty acid-binding protein at baseline were related to future PDD as analyzed by Cox proportional hazards regression models. Combined, these early biomarkers predicted PDD with high accuracy (hazard ratio, 11.8; 95% CI, 3.3-42.1; P = .0001) after adjusting for possible confounders. CONCLUSIONS AND RELEVANCE: The analyzed CSF biomarkers have potential usefulness as a diagnostic tool in patients with parkinsonism. In PD, high neurofilament light chain protein, low Aβ1-42, and high heart fatty acid-binding protein were related to future PDD, providing new insights into the etiology of PDD.

Ort, förlag, år, upplaga, sidor
American Medical Association , 2015. Vol. 72, nr 10, s. 1175-1182
Nationell ämneskategori
Neurovetenskaper Neurologi
Identifikatorer
URN: urn:nbn:se:umu:diva-111148DOI: 10.1001/jamaneurol.2015.1449ISI: 000362963000014PubMedID: 26258692OAI: oai:DiVA.org:umu-111148DiVA, id: diva2:868720
Tillgänglig från: 2015-11-11 Skapad: 2015-11-06 Senast uppdaterad: 2019-01-23Bibliografiskt granskad
Ingår i avhandling
1. The biology of cognitive decline and reduced survival in Parkinson disease: prognostic factors in a population-based cohort
Öppna denna publikation i ny flik eller fönster >>The biology of cognitive decline and reduced survival in Parkinson disease: prognostic factors in a population-based cohort
2019 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
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.

Ort, förlag, år, upplaga, sidor
Umeå: Umeå universitet, 2019. s. 67
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 2006
Nyckelord
Parkinson disease, multiple system atrophy, progressive supranuclear palsy, natural history, cognitive impairment, dementia, predictors of mortality, cerebrospinal fluid biomarkers, prospective, population-based
Nationell ämneskategori
Neurovetenskaper
Forskningsämne
neurologi
Identifikatorer
urn:nbn:se:umu:diva-155588 (URN)978-91-7855-022-7 (ISBN)
Disputation
2019-02-15, Sal D, byggnad 1D, våning 9, Norrlands universitetssjukhus, Umeå, 13:00 (Svenska)
Opponent
Handledare
Tillgänglig från: 2019-01-25 Skapad: 2019-01-23 Senast uppdaterad: 2019-01-24Bibliografiskt granskad

Open Access i DiVA

Fulltext saknas i DiVA

Övriga länkar

Förlagets fulltextPubMed

Personposter BETA

Bäckström, David CEriksson Domellöf, MagdalenaLinder, JanTrupp, MilesForsgren, Lars

Sök vidare i DiVA

Av författaren/redaktören
Bäckström, David CEriksson Domellöf, MagdalenaLinder, JanTrupp, MilesForsgren, Lars
Av organisationen
Klinisk neurovetenskap
I samma tidskrift
JAMA Neurology
NeurovetenskaperNeurologi

Sök vidare utanför DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetricpoäng

doi
pubmed
urn-nbn
Totalt: 246 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf