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@PHDTHESIS{Hermann:282309,
      author       = {Hermann, Peter},
      title        = {{B}iomarker in der {D}iagnostik und
                      {D}ifferentialdiagnostik der vaskulären {D}emenz bei
                      zerebraler {M}ikroangiopathie | {B}iomarker in the
                      differential diagnosis of vascular dementia caused by
                      cerebral small vessel disease},
      school       = {Georg-August-Universität Göttingen},
      type         = {Dissertation},
      reportid     = {DZNE-2025-01279},
      pages        = {78 p.},
      year         = {2019},
      note         = {Dissertation, Georg-August-Universität Göttingen, 2019},
      abstract     = {AIMS AND BACKGROUND: Besides Alzheimer’s disease (AD),
                      Vascular dementia (VD) caused by cerebral small vessel
                      disease (CSVD) is one of the most common causes of dementia
                      but differential diagnosis, especially the discrimination of
                      VD and AD, is still difficult. Established imaging markers
                      of VD (e.g. MRI white matter hyperintensities [WMH]) are not
                      specific and can be found in aged healthy people or in
                      patients with mixed dementia (MD). The aim of this project
                      was to identify and validate biomarkers that may become
                      useful in the differential diagnoses of dementia by
                      analyzing data from a case-control study. METHODS: Between
                      2007 and 2012, 236 patients were recruited for the study
                      “Investigation of the prognostic potential cerebrospinal
                      fluid biomarkers in the differential diagnosis of CJD and
                      vascular dementia”. Inclusion criteria were the presence
                      of WMH on MRI scans and the absence of clinical or
                      radiological evidence of a stroke within the last 8 weeks.
                      Data from MRI, medical history, and neuropsychological
                      assessment as well as biological samples (blood and
                      cerebrospinal fluid [CSF]) were collected. This thesis
                      includes three published articles that used data from the
                      aforementioned study. RESULTS: Publication I: CSF biomarkers
                      and neuropsychological profiles in patients with cerebral
                      small-vessel disease: CSF Tau and pTau were significantly
                      elevated in the groups with AD and MD compared to VD and
                      controls (CSVD without cognitive deficits). The albumin
                      ratio (CSF/serum) was elevated in VD compared to all other
                      groups. Analyses of cognitive assessment scales showed that
                      the ratio of scores for memory and executive functions was
                      elevated in VD compared to MD and controls. For AD patients,
                      no data was available. A negative correlation between
                      albumin ratio and executive function could be observed in
                      VD, MD and controls. Publication II: Cytokine profiles and
                      role of cellular PrP in patients with vascular dementia and
                      vascular encephalopathy: Different patterns of alterations
                      of several anti- and pro-inflammatory cytokines in CSF and
                      serum were identified in groups with AD, VD, VE (vascular
                      encephalopathy: CSVD without cognitive deficits. In patients
                      with CSVD (VD + VE), cytokine-profiles were rather
                      associated with WMH severity than with cognitive
                      performance. IL-6 (CSF) and MIP-1b (CSF and serum) were
                      elevated in AD and VD. PrPC concentrations were altered in
                      VE and VD compared to AD and controls (elevated in CSF,
                      decreased in serum). Publication III: Cerebrospinal fluid
                      biomarkers of Alzheimer’s disease show different but
                      partially overlapping profile compared to Vascular dementia:
                      Concentrations of several potential and established CSF
                      biomarkers were analyzed and results were validated in an
                      independent cohort. AD groups showed a characteristic
                      profile (Tau and pTau increased, aβ1-42 decreased).
                      Subgroup analyses showed no significant differences between
                      rapid-progressive AD und AD as well as between VE and VD.
                      S100b and YKL-40 were increased in AD, proteins 14-3-3 were
                      increased in AD and VD compared to controls. Single
                      biomarkers could differentiate AD and VD in a satisfying way
                      but a high diagnostic accuracy could be achieved by applying
                      the Aβ1-42/pTau ratio. CONCLUSIONS: The articles give
                      conclusive data that may become useful in the clinical
                      differentiation of AD, VD and MD. The results of Tau and
                      amyloid marker analyses are in line with data that was found
                      in the literature and with recently proposed diagnostic
                      research criteria that aim to diagnose different dementia
                      entities based on biomarkers rather than on clinical
                      syndromes. Concerning the elevation of the albumin ratio (as
                      a marker of blood-brain-barrier disturbance), the findings
                      are coherent with common models of the pathologic mechanisms
                      of VD and have been reproduced by other groups.},
      cin          = {AG Zerr},
      cid          = {I:(DE-2719)1440011-1},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)11},
      url          = {https://pub.dzne.de/record/282309},
}