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| Home > Documents in Process > Biomarker in der Diagnostik und Differentialdiagnostik der vaskulären Demenz bei zerebraler Mikroangiopathie | Biomarker in the differential diagnosis of vascular dementia caused by cerebral small vessel disease |
| Home > Documents in Process > Biomarker in der Diagnostik und Differentialdiagnostik der vaskulären Demenz bei zerebraler Mikroangiopathie | Biomarker in the differential diagnosis of vascular dementia caused by cerebral small vessel disease |
| Dissertation / PhD Thesis | DZNE-2025-01279 |
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.
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