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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},
}