oru.sePublikationer
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Fibrinolysis and von Willebrand factor in Alzheimer's disease and vascular dementia: a case-referent study
Örebro University, School of Health and Medical Sciences.ORCID iD: 0000-0002-2869-7239
Umeå universitet.
Örebro University, School of Health and Medical Sciences.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Introduction: The importance of vascular risk factors for Alzheimer’s disease (AD) is not settled. Our aim was to compare patients with AD or vascular dementia (VaD) with non-demented subjects with regard to endothelial derived fibrinolytic and hemostatic factors.

Materials and methods: In a cross-sectional mono-center case-referent study in Örebro, Sweden, we consecutively included 95 patients with AD and 55 with VaD and 154 non-demented active seniors (AS). Plasma biomarkers including the endothelial derived fibrinolytic factors: mass concentrations of tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), tPA/PAI-1 complex and von Willebrand factor (vWF), as well as clinical data were analyzed.

Results: None of the endothelial derived fibrinolytic markers or vWF differed between AD vs. VaD. In comparison with the AS group, tPA was higher in AD (p=0.001) and VaD (p=0.023) but its inhibitor, PAI-1 mass concentration did not differ significantly; tPA/PAI-1 complex was higher in both VaD (p=0.038) and AD (p=0.005). vWF concentration was lower in the AS group (p<0.001) than in both dementia groups.

Conclusion: Thus, endothelial derived fibrinolytic factors, tPA/PAI-1 complex and vWF, discriminated between the reference group of non-demented elderly and the AD and VaD groups, but not between AD and VaD. This suggests similar disturbances for endothelial derived fibrinolytic and hemostatic factors among AD and VaD patients and may reflect shared vascular pathophysiological mechanisms in the dementias.

Keyword [en]
vascular dementia, Alzheimer’s disease, fibrinolysis, hemostasis, von Willebrand factor
National Category
Geriatrics Medical and Health Sciences
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-7845OAI: oai:DiVA.org:oru-7845DiVA: diva2:234428
Available from: 2009-09-09 Created: 2009-09-08 Last updated: 2016-12-08Bibliographically approved
In thesis
1. Vascular mechanisms in dementia with special reference to folate and fibrinolysis
Open this publication in new window or tab >>Vascular mechanisms in dementia with special reference to folate and fibrinolysis
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The aim of this thesis was to study the biomarker homocysteine and other novel potential vascular risk factors for dementia. In an out-patient based study of a cohort of 926 consecutive subjects referred to our Memory Unit during 1996―2000, serum-folate was lower and total plasma homocysteine (tHcy) and serum methyl malonate were higher in subjects being prescribed with B12. In the subgroup diagnosed with dementia and with a positive family history of dementia, tHcy was higher than in the subgroup diagnosed as non-demented. It is necessary to supplement subjects with vitamin B12 deficiency with B12, but our results indicate that it is not sufficient with B12 alone because this gives rise to intracellular folate deficiency. We also found indications of a genetic component in dementia because tHcy was higher in the group with a positive family history of dementia. These findings prompted further studies of homocysteine metabolism. The frequency of mutations in the gene for folate receptor-α (FOLR-1), and the fibrinolytic pattern in dementia and non-dementia were studied in the two cohorts DGM (n=300) and AS (n=389). The DGM cohort is a consecutive series of subjects attending our Memory Care Unit for investigation of suspected cognitive problems or dementia between 2003 - 2007. The AS (= active seniors) cohort comprises retired, apparently healthy subjects from central Sweden, actively participating in study circles. A rare haplotype in the FOLR-1, with mutations in two nearby loci, was discovered, possibly associated with lower serum-folate and higher tHcy concentrations and was more frequent in the DGM group. The transport of folate to the CSF was studied in the DGM-cohort. Dementia with a vascular component was associated with a lower CSF to serum folate ratio indicative of reduced transport of folate to the CSF and further to the brain. The vascular endothelial derived fibrinolytic markers tPA, tPA/PAI-1-complex, and vWF were not only higher in vascular dementia (VaD) but also in Alzheimer’s Disease (AD) when compared to the AS group. The impaired fibrinolytic activity in both vascular dementia and in AD is a novel finding, signifying a vascular component in the development of dementia. In conclusion we found that both hereditary and nutritional background factors were linked to dementia and furthermore that a dysregulated fibrinolysis was linked to both VaD and AD.

Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2009. 65 p.
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 33
Keyword
dementia, Alzheimer’s disease, vascular dementia, folate, homocysteine, vitamin B12, CSF/Serum folate ratio, fibrinolysis, tPA, PAI-1
National Category
Geriatrics Medical and Health Sciences
Research subject
Geriatrics; Medicine
Identifiers
urn:nbn:se:oru:diva-7785 (URN)978-91-7668-682-9 (ISBN)
Public defence
2009-10-06, Bohmanssonsalen, Universitetssjukhuset Örebro, Örebro, 09:00 (English)
Opponent
Supervisors
Available from: 2009-09-02 Created: 2009-09-01 Last updated: 2016-12-06Bibliographically approved

Open Access in DiVA

fulltext(129 kB)342 downloads
File information
File name FULLTEXT01.pdfFile size 129 kBChecksum SHA-512
18d482681ce2e4b71990a490c9045a653ba0ae9603ea0db08452e95ca6930e31e42dfca79728aaac3770d656ca13c5a72440ec18fd7b72b7983b292777b041f6
Type fulltextMimetype application/pdf

Search in DiVA

By author/editor
Hagnelius, Nils-OlofNilsson, Torbjörn K.
By organisation
School of Health and Medical Sciences
GeriatricsMedical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 342 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Total: 143 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf